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  • 1.
    Akhter, Tansim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Marita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Naessen, Tord
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia: A seven-year follow-up.2019Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, artikel-id S0021-9150(19)30449-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia.

    METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis.

    RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT.

    CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.

  • 2.
    Akhter, Tansim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Wikström, Gerhard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Larsson, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Bondesson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Hedeland, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Naessén, Tord
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with and without preeclampsia2018Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 275, s. E69-E70Artikel i tidskrift (Övrigt vetenskapligt)
  • 3.
    Aldi, Silvia
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Eriksson, Linnea
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Kronqvist, Malin
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Lengquist, Mariette
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Löfling, Marie
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Folkersen, Lasse
    Tech Univ Denmark, Ctr Biol Sequence Anal, Copenhagen, Denmark.
    Matic, Ljubica P.
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Maegdefessel, Lars
    Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden;Tech Univ Munich, Dept Vasc Surg, D-80333 Munich, Germany.
    Grinnemo, Karl-Henrik
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Li, Jin-Ping
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Österholm, C.
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Hedin, Ulf
    Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden.
    Dual roles of heparanase in human carotid plaque calcification2019Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 283, s. 127-136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-beta-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro.

    Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively.

    Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation.

    Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.

  • 4.
    Bennet, A. M.
    et al.
    Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm.
    Van Maarle, M.
    Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm.
    Hallqvist, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Preventionsmedicin.
    Morgenstern, R.
    Unit of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Frostegård, J.
    Wiman, B.
    Division of Coagulation Research, Karolinska University Hospital, Stockholm, Sweden.
    Prince, J. A.
    de Faire, U.
    Association of TNF-α serum levels and TNFA promoter polymorohisms with risk of myocardial infarction2006Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 187, nr 2, s. 408-414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Elevated levels of tumor necrosis factor-alpha (TNF-α), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (−1031C/T, −863C/A −857T/C, −308G/A, −238G/A), protein levels of TNF-α and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-α levels, with the highest compared to the lowest TNF-α quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-α levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-α levels were seen among smokers (but not among non-smokers) carrying the −857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-α levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.

  • 5.
    Björck, Martin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Ravn, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Nilsson, T K
    Wanhainen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Nilsson, P M
    Blood cell telomere length among patients with an isolated popliteal artery aneurysm and those with multiple aneurysm disease2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 219, nr 2, s. 946-950Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    Short relative telomere length (RTL) is associated with vascular ageing, inflammation and cardiovascular risk factors. Previous studies have reported an association between abdominal aortic aneurysm and short RTL. The presence of atherosclerosis among patients with aneurysm disease may, however, be a confounder. The aim was to explore the associations between short RTL and aneurysm disease, by comparing patients with isolated popliteal artery aneurysms with those having multiple aneurysms.

    DESIGN AND PATIENTS:

    DNA was retrieved from 183 patients with popliteal artery aneurysm (PAA). They were all examined with ultrasound at the time of blood-sampling, and had a total of 423 aneurysms (range 1-7, mean 2.3/patient).

    METHODS:

    TL was measured with Real-Time PCR, RTL was calculated by comparing with three reference populations.

    RESULTS:

    Patients with bilateral PAAs had a mean RTL of 0.985 vs. 1.038 with unilateral PAAs (P=0.326). Patients with abdominal aortic aneurysm had RTL 1.035, vs. 0.999 without (P=0.513). No difference was seen with or without femoral or iliac aneurysms. Fifty-six patients with isolated PAA at surgery and at re-examination had RTL 0.974, vs. 1.033 who had >1 aneurysm (P=0.308). RTL was not associated with the number of aneurysms at re-examination (P=0.727, one-way ANOVA). There was a trend towards shorter RTL among active smokers (0.93 vs. 1.04, P=0.066).

    CONCLUSIONS:

    No association between short RTL and multiple aneurysm disease was found. The previously reported association between AAA and short RTL may be secondary to cardiovascular risk factors, rather than by aneurysm disease.

  • 6.
    Carlson, Lars A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Fröberg, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Oro, L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy1972Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 16, nr 3, s. 359-368Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A case of massive hypertriglyceridemia with fasting plasma triglycerides around 100 mmoles/l is described. Large amounts of chylomicra were present in fasting plasma and the amounts of low-density and high-density lipoproteins were very low. Postheparin plasma lipolytic activity was normal and intravenous heparin rapidly cleared the patient's abnormally prolonged alimentary lipemia with a concomitant rise in plasma free fatty acid levels.

    Nicotinic acid or nictotinamide given in doses of 3 g or more daily reduced plasma triglyceride levels to about 2–3 mmoles/1 and raised the reduced levels of low and high-density lipoproteins. The mode of onset of this therapeutic effect was slow and the effect persisted for several weeks after withdrawal of either nicotinic acid or nicotinamide.

    The pathogenesis of the hypertriglyceridemia as well as the mode of action of nicotinic acid and nicotinamide is discussed.

  • 7.
    Carlson, Lars A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Walldius, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Butcher, R.W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Effect of chlorophenoxyisobutyric acid (CPIB) on fat-mobilizing lipolysis and cyclic AMP levels in rat epididymal fat1972Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 16, nr 3, s. 349-357Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High concentrations of chlorophenoxyisobutyric acid (CPIB) reduced basal glycerol release from rat epididymal fat pads in vitro and antagonized the lipolytic effects of noradrenaline. Furthermore, very high concentrations of CPIB significantly antagonized the effects or noradrenaline or ACTH on cyclic AMP accumulation by isolated rat adipocytes. These data are not incompatible with the hypothesis that a primary mechanism in the hypolipidemic action of CPIB is to lower the levels of cyclic AMP in adipose tissue, resulting in decreased hormone-sensitive lipase activity and/or increased lipoprotein lipase activity.

  • 8.
    Carlsson, Axel C
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Jansson, Jan-Håkan
    Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Umeå, Sweden.
    Söderberg, Stefan
    Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden.
    Ruge, Toralph
    Dept of Medicine Solna, Karolinska Institutet and Function of Emergency Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ärnlöv, Johan
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Sciences, Dalarna University, Falun, Sweden.
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, s. 41-46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS:

    Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

    METHODS:

    We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

    RESULTS:

    An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

    CONCLUSIONS:

    As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

  • 9.
    Carlsson, Axel C
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly2014Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, nr 1, s. 236-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 10. Delgado-Lista, J.
    et al.
    Perez-Martinez, P.
    Garcia-Rios, A.
    Phillips, C. M.
    Williams, C. M.
    Gulseth, H. L.
    Helal, O.
    Blaak, E. E.
    Kiec-Wilk, B.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Drevon, C. A.
    Defoort, C.
    Saris, W. H.
    Wybranska, I.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lovegrove, J. A.
    Roche, H. M.
    Lopez-Miranda, J.
    Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: From the LIPGENE study2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 214, nr 1, s. 110-116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). Methods: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. Results: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. Conclusions/interpretation: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.

  • 11.
    den Hoed, Marcel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J
    Almgren, Peter
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Engström, Gunnar
    de Faire, Ulf
    Hedblad, Bo
    Humphries, Steve E
    Lindgren, Cecilia M
    Morris, Andrew P
    Östling, Gerd
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Tremoli, Elena
    Hamsten, Anders
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Melander, Olle
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb2015Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 239, nr 2, s. 304-310Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.

    OBJECTIVES: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.

    METHODS: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.

    RESULTS: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).

    CONCLUSIONS: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

  • 12.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Apolipoprotein B/A-I ratio related to visceral but not to subcutaneous adipose tissue in elderly Swedes2010Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 211, nr 2, s. 656-659Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate whether the amount of visceral (VAT) or subcutaneous adipose tissue (SAT) independently of the other can determine the apolipoprotein (apo)B/A-I ratio. METHODS: VAT and SAT areas were assessed using magnetic resonance imaging in 247 randomly selected 70-year-old men and women who did not use lipid-lowering drugs. Their adipose tissue areas were compared to their apoB and apo A-I levels and to their apoB/A-I ratios. RESULTS: The VAT area and the gender were significantly related to the apoB/A-I ratio whereas the SAT area was not. There was a positive relationship between the VAT area and the apoB/A-I ratio. CONCLUSION: A positive relationship was established between the amount of VAT and the apoB/A-I ratio, whereas there was no relationship between the amount of SAT and the apoB/A-I ratio. This observation supports the notion that VAT is metabolically active.

  • 13.
    Eriksson, Jan W
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Burén, Jonas
    Svensson, Maria
    Olivecrona, Thomas
    Olivecrona, Gunilla
    Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects.2003Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 166, nr 2, s. 359-67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/AIM: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL).

    SUBJECTS AND METHODS: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin.

    RESULTS: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0+/-0.4 vs 2.0+/-0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by approximately 35-55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR.

    CONCLUSION: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.

  • 14.
    Feldreich, Tobias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. School of Health and Social Studies, Dalarna University, Falun, .
    Carlsson, Axel C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. School of Health and Social Studies, Dalarna University, Falun, .
    The association between serum cathepsin L and mortality in older adults2016Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 109-116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 15. Ferguson, Jane F.
    et al.
    Phillips, Catherine M.
    McMonagle, Jolene
    Perez-Martinez, Pablo
    Shaw, Danielle I.
    Lovegrove, Julie A.
    Helal, Olfa
    Defoort, Catherine
    Gjelstad, Ingrid M. F.
    Drevon, Christian A.
    Blaak, Ellen E.
    Saris, Wim H. M.
    Leszczynska-Golabek, Iwona
    Kiec-Wilk, Beata
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Karlström, Brita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lopez-Miranda, Jose
    Roche, Helen M.
    NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids2010Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 211, nr 2, s. 539-544Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene-nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS). Methods: Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene-nutrient interactions. Results: Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene-nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes. Conclusions: Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.

  • 16. Garcia-Rios, Antonio
    et al.
    Delgado-Lista, Javier
    Perez-Martinez, Pablo
    Phillips, Catherine M.
    Ferguson, Jane F.
    Gjelstad, Ingrid M. F.
    Williams, Christine M.
    Karlström, Brita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kiec-Wilkh, Beata
    Blaak, Ellen E.
    Lairon, Denis
    Planells, Richard
    Malczewska-Malec, Malgorzata
    Defoort, Catherine
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Saris, Wim H. M.
    Lovegrove, Julie A.
    Drevon, Christian A.
    Roche, Helen M.
    Lopez-Miranda, Jose
    Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, nr 2, s. 416-422Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients. Methods: Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study. Results: Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P < 0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P < 0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P = 0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort. Conclusion: Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS. 

  • 17. Gonzalez, Manuel
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Soderberg, Stefan
    Leptin and endothelial function in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, nr 2, s. 485-490Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear. Aim: To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community. Methods: This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored. Results: In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure. Conclusion: Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function.

  • 18.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ahlström, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort2015Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 238, nr 2, s. 420-426Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Diseases with abnormal levels of parathyroid hormone (PTH) and calcium, such as primary and secondary hyperparathyroidism, are associated with an increased risk of cardiovascular morbidity and mortality. However, there is paucity on the association between calcium, PTH and abnormalities in the vascular system in the general population.

    METHODS:

    In the PIVUS study (Prospective Investigation of the Vasculature in Uppsala Seniors), a community based cohort of 70-year old men and women (n = 1016), the associations between s-calcium, p-PTH and endothelial function, arterial stiffness and blood pressures were investigated, adjusting for cardiovascular risk factors and mineral metabolism.

    RESULTS:

    In multivariable linear regression models 1 SD increase in calcium was associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and 0.06 decrease in common carotid artery distensibility (p < 0.001) indicative of increased arterial stiffness. Further, calcium was associated with increasing calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in calcium (p < 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg increase in intra-arterially measured brachial artery systolic and diastolic blood pressures, respectively (p < 0.01), as well as 1.6 and 0.9 mmHg increase in calculated central systolic and diastolic blood pressures (p < 0.05). PTH was not associated with arterial stiffness, endothelial function or pulse pressure.

    CONCLUSION:

    In a large community-based sample of elderly, calcium was independently associated with increased arterial stiffness, and PTH independently to intra-arterial peripheral and calculated central blood pressures. The findings indicate a possible link between the vasculature and mineral metabolism.

  • 19.
    Hansen, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Söderberg, S.
    Hulthe, J.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, nr 1, s. 163-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS: Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS: VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION: Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

  • 20.
    Hansen, Tomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Wanhainen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lymph nodes as a potential pitfall in carotid plaque imaging with FDG-PET/CT2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 215, nr 1, s. 247-248Artikel i tidskrift (Refereegranskat)
  • 21. Harrison, Seamus C.
    et al.
    Zabaneh, Delilah
    Asselbergs, Folkert W.
    Drenos, Fotios
    Jones, Gregory T.
    Shah, Sonia
    Gertow, Karl
    Sennblad, Bengt
    Strawbridge, Rona J.
    Gigante, Bruna
    Holewijn, Suzanne
    De Graaf, Jacqueline
    Vermeulen, Sita
    Folkersen, Lasse
    van Rij, Andre M.
    Baldassarre, Damiano
    Veglia, Fabrizio
    Talmud, Philippa J.
    Deanfield, John E.
    Agu, Obi
    Kivimaki, Mika
    Kumari, Meena
    Bown, Matthew J.
    Nyyssonen, Kristiina
    Rauramaa, Rainer
    Smit, Andries J.
    Franco-Cereceda, Anders
    Giral, Philippe
    Mannarino, Elmo
    Silveira, Angela
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    de Borst, Gert J.
    van der Graaf, Yolanda
    de Faire, Ulf
    Baas, Annette F.
    Blankensteijn, Jan D.
    Wareham, Nicholas J.
    Fowkes, Gerry
    Tzoulaki, Ionna
    Price, Jacqueline F.
    Tremoli, Elena
    Hingorani, Aroon D.
    Eriksson, Per
    Hamsten, Anders
    Humphries, Steve E.
    A gene-centric study of common carotid artery remodelling2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 226, nr 2, s. 440-446Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA). Results: rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08-0.18 mm, P = 8.2 x 10(-8)). A proxy SNP (rs4916251, R-2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case-control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03-1.17, p = 2.8 x 10(-3), I-2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling. Conclusions: Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development.

  • 22.
    Helmersson, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Enheten för klinisk näringsforskning.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Enheten för klinisk näringsforskning.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Enheten för klinisk näringsforskning.
    Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F(2)-isoprostane formation in elderly men2005Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 181, nr 1, s. 201-207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F(2alpha) (PGF(2alpha)) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha)), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF(2alpha) (an F(2)-isoprostane, indicator of oxidative stress), and serum alpha-tocopherol were quantified in a population-based sample (n = 642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF(2alpha), P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF(2alpha) was increased (P < 0.01) and alpha-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF(2alpha), IL-6 and 8-iso-PGF(2alpha) compared non-smokers. This is the first study to show that smokers have increased PGF(2alpha) formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.

  • 23.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, nr 2, s. 408-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    METHODS

    This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    RESULTS

    U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb.

    CONCLUSION

    This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.

  • 24.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Härmä, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort2014Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 234, nr 1, s. 108-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death.

    METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.

    RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P < 0.001, compared to all three biomarkers normal).

    CONCLUSIONS: This study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

  • 25. Hoffmann, Christian J.
    et al.
    Hohberg, Margret
    Chlench, Sven
    Maroski, Julian
    Drab, Marek
    Siegel, Günter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Pries, Axel R.
    Zakrzewicz, Andreas
    Suppression of zinc finger protein 580 by high oxLDL/LDL-ratios is followed by enhanced expression of endothelial IL-82011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 216, nr 1, s. 103-108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The Interleukin 8 (IL-8) response of endothelial cells to lipoproteins has well known implications for the development and progression of atherosclerosis. In this study we sought for the role of zinc finger protein 580 (ZNF580) in the endothelial IL-8 response to lipoproteins. Methods: In human umbilical vein endothelial cells (HUVEC) ZNF580 and IL-8 levels were examined by real-time-RT-PCR, immunoblotting and immunostaining or ELISA, respectively. Results: ZNF580 is located in the nucleus and regulated by LDL and HDL depending on the oxLDL/LDL-ratio but not by TNF alpha. IL-8 expression profiles are inversely influenced by the oxLDL/LDL-ratio, both in vitro and in vivo. Knock down of ZNF580 enhances the expression and release of IL-8 and increases monocyte arrest under flow conditions in vitro. Conclusions: ZNF580 is a novel factor in the lipoprotein-dependent regulation of IL-8 and monocyte arrest. Therefore it may be a new potential target for intervention in atherosclerosis.

  • 26. Holme, Ingar
    et al.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jardine, Alan
    Holdaas, Halvard
    Comparison of predictive ability of lipoprotein components to that of traditional risk factors of coronary events in renal transplant recipients2010Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 208, nr 1, s. 234-239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Risk factors for major adverse coronary events (MACE) in renal transplant recipients are often different from those of non-transplanted populations. We compared the predictive power of lipoprotein components (LC) to that of more traditional risk factors such as serum creatinine, diabetes and inflammation measured by C-reactive protein (CRP) in the assessment of lescol in renal transplantation (ALERT) trial population. METHODS: From the 2102 randomized patients in ALERT we selected 1734 patients with a complete set of risk and adjustment factors used in the study. Cox regression analysis was used to estimate relationships between baseline values of risk factors and first occurrence of MACE. Chi square statistics, receiver operating characteristics (ROC) and net reclassification improvement (NRI) were used to compare the information value of different risk factors. RESULTS: Atherogenic LC and especially non-high density cholesterol (nHDL-C) were as predictive as creatinine and nHDL-C was about as predictive as diabetes. CRP, body mass index, hypertension and glucose had less prediction ability than nHDL-C. The rank order of prediction was the same in the two treatment groups. By regression modelling the actual MACE risk reduction from 6 weeks onwards was well predicted from the difference in LC at 6 week. CONCLUSION: LC and especially nHDL-C predicted MACE at least as good as creatinine. Diabetes was about equally good as nHDL-C to predict MACE occurrence. Inflammation had less prediction ability than the other factors. Treated levels of atherogenic LC predicted MACE risk reduction well.

  • 27. Holmlund, A.
    et al.
    Hulthe, J.
    Millgård, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sarabi, Mahziar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals2002Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 165, nr 2, s. 271-276Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.

  • 28.
    Holmlund, Anders
    et al.
    Uppsala Univ Reg Gavleborg, Cty Hosp Gavle, Dept Periodontol, Ctr Res & Dev, Gavle, Sweden..
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Oral health and cardiovascular disease risk in a cohort of periodontitis patients2017Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 262, s. 101-106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: The aim of this study was to determine whether oral health is uniformly associated with three different cardiovascular diseases (CVDs), including myocardial infarction (MI), stroke, and heart failure (HF), which has not been studied previously. Methods: A full mouth investigation was performed in 8999 individuals referred to a specialized periodontology clinic between 1979 and 2012. The number of deepened pockets (NDP), number of teeth (NT), and bleeding on probing (BOP) were investigated. Incident CVD diagnosis was obtained from the Swedish cause of death and the hospital discharge registers. Results: During a median follow-up time of 15.8 years (153,103 person years at risk), 1338 incident cases of fatal/non-fatal CVD occurred (672 fatal/non-fatal MI, 545 stroke and 302 HF). When NT, BOP and NDP were all included in the same model with age, sex, smoking, calendar time, and education level, NT and NDP, but not BOP, were significantly related to future CVD (combined end-point, p=0.0003 for NT and p =0.007 for NDP). In similar analyses of 3 separate CVD outcomes, NT was significantly related to MI, with an incidence rate ratio (IRR) for a given interquartile range change of 0.90 (95% CI 0.82=0.99) and to HF, with an IRR of 0.87 (95% CI 0.77-0.99). However, NT was not significantly related to stroke. BOP and NDP were not significantly related to any of the three separate CVD outcomes. Conclusion: Oral health, mainly represented by NT, was related to incident MI and HF, but not to incident stroke. Therefore, oral health does not seem to relate to all major CV disorders in a similar fashion.

  • 29.
    Huang, Biying
    et al.
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94304 USA.;Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden..
    Svensson, Per
    Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden..
    Sundstrom, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94304 USA.
    Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies2016Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 52-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years). Methods: Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique. Results: We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR<5%); and ten were replicated in ULSAM (p<0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease. Conclusions: The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 30.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasan, Ramachandran S.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Blomhoff, Rune
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 206, nr 1, s. 239-244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly. METHODS: We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD. RESULTS: RBP4 concentrations were positively correlated with serum triglycerides (r=0.30; P<0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% confidence interval (CI), 0.99-1.37 and 1.05-1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction. CONCLUSION: In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.

  • 31.
    Ingelsson, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Polymorphisms in the estrogen receptor alpha gene and endothelial function in resistance and conduit arteries in the elderly2008Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 199, nr 1, s. 162-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Prior evidence suggests an important role for estrogen in the regulation of endothelium-dependent vasodilation, but the mechanisms modulating this are not known. Our aim was to examine the relations of single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) to endothelium-dependent vasodilation.

    METHODS:

    We evaluated 959 70-year-old participants (51% men) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, using invasive forearm technique with intra-brachial infusion of acetylcholine (EDV; reflecting vasodilation in resistance arteries), and brachial artery ultrasound to assess flow-mediated vasodilation (FMD; reflecting vasodilation in conduit arteries). We genotyped 25 common SNPs in the ESR1 gene, and related them to EDV and FMD using multivariable linear regression, adjusting for sex and other potential confounders, such as major cardiovascular risk factors and medications. Haplotypes were estimated using the PHASE software.

    RESULTS:

    We observed an association between rs1709183 in the ESR1 gene and EDV (nominal P=0.0012), with a lower EDV in carriers of the minor allele (C). This association remained significant after adjustment for multiple testing (empirical P=0.031, obtained using bootstrap re-sampling). Two ESR1 haplotypes in the block containing rs1709183 were associated with EDV (individual haplotype P=0.0015 and P=0.025); the directions of effect were consistent with individual SNP analyses. FMD was not associated with any of the ESR1 SNPs.

    CONCLUSIONS:

    In our community-based study of elderly, a polymorphism in the estrogen receptor alpha gene was associated with endothelium-dependent vasodilation in resistance, but not conduit arteries. Our findings should stimulate further exploration in other settings.

  • 32.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Arterial compliance influences the measurement of flow-mediated vasodilation, but not acetylcholine-mediated forearm blood flow. The prospective investigation of the vasculature in uppsala seniors (PIVUS) study2007Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 190, nr 1, s. 212-215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Flow-mediated vasodilation (FMD) is low even in healthy elderly and therefore relations between FMD and cardiovascular risk factors might be hard to evaluate in the elderly. Using data from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we investigated if a reduced arterial distensibility could influence FMD measurements. Methods: In the population-based PIVUS study (1016 subjects aged 70), assessments of arterial distensibility by ultrasound in the carotid artery (CCA) and FMD were performed. Endothelium-dependent vasodilation was also evaluated with the invasive forearm technique with acetylcholine (EDV) and by pulse wave analysis following terbutaline injection. A poor CCA distensibility was defined as <25th percentile in the healthy part of the population (n = 131). Results: FMD was significantly related to the Framingham risk score only in those with a good CCA distensibility (r = -0.16, p = 0.0081 versus r = -0.06, p = 0.17 in those with a poor CCA distensibility, p = 0.0001 for difference). In contrast, the relationship between EDV and coronary risk was not affected by CCA distensibility (r = -0.11, p = 0.018 versus r = -0.13, p = 0.027). Conclusions: A reduced CCA distensibility could in part explain the low FMD values in the elderly. FMD correlated to the Framingham risk score only in those with a good CCA distensibility, exemplifying a limitation of the use of FMD in elderly populations. On the contrary, EDV was not affected by arterial stiffness.

  • 33.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2008Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 196, nr 2, s. 795-802Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Only a few previous studies have investigated endothelium-dependent vasodilation in the metabolic syndrome (MetS). In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to assess vasodilation in conduit and resistance arteries were evaluated in relation to the MetS and insulin resistance.

    Methods: In this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline.

    Results: EDV was lower in subjects with the MetS (NECP/ATP III-criteria, prevalence 23%) compared to those without (p < 0.0001), and declined with increasing number of MetS criteria (p < 0.0001), after adjustment for coronary heart disease, stroke and cardiovascular medication. Also a reduced pulse wave response (p=0.015), but not FMD (p=0.64), was seen in those with the MetS. EDV and the pulse wave response, but not FMD, were inversely related to insulin resistance evaluated by the HOMA index. Also endothelium-independent vasodilation (EIDV) induced by intra-brachial infusion of sodium nitroprusside was impaired in subjects with MetS and in insulin resistance.

    Conclusions: Vasodilation evaluated with the invasive forearm technique and pulse wave analysis with a beta-2 agonist, but not FMD, was reduced in elderly subjects with the MetS and was related to insulin resistance. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with the MetS.

  • 34.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Flow-mediated vasodilation over five years in the general elderly population and its relation to cardiovascular risk factors2014Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, nr 2, s. 666-670Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Flow-mediated vasodilation (FMD) has previously been shown to be related to cardiovascular risk factors in cross-sectional studies. The present study aims to investigate how FMD changes over time, and determine whether this change is paralleled by changes in cardiovascular risk factors. Methods: Of the participants in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 750 individuals had measurements made of FMD in the brachial artery both at the ages of 70 and 75 years. In addition, the change over the 5 years in carotid artery intima-media thickness (IMT) was monitored, as well as traditional cardiovascular risk factors. Results: While no significant change in FMD occurred during the 5-year period (+0.1%, p = 0.53), large changes could be seen at the individual level. The Framingham risk score (excluding the age-variable) increased during the follow-up period (+0.54, p < 0.001). This change was inversely related to the individual change in FMD (beta -0.15, 95% CI -0.29 to 0.0059, p = 0.041). Of the eight individual CV risk factors tested, the change in FMD was only related to the change in LDL-cholesterol (inversely, p = 0.0028). The change in FMD was not related to the change in IMT seen over the 5-year period (p = 0.41). Conclusion: While no change was seen in the mean FMD over a five-year period in elderly subjects attending both examinations despite ageing and a change in several risk factors, the individual change was mainly related to the change in LDL-cholesterol, further emphasizing the important role of lipids to determine vasoreactivity.

  • 35.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasodilation in resistance arteries is related to the apolipoprotein B/A1 ratio in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2007Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 190, nr 2, s. 378-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent studies have shown the apolipoprotein B to apolipoprotein A1 ratio (apoB/A1) to be superior to LDL-cholesterol measurements to predict cardiovascular events. The present study aims to relate apoB/A1 to endothelium-dependent vasodilation, an early marker of atherosclerosis, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. Methods and results: In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. EDV and the pulse wave response, but not FMD, were related to apoB/A1 levels (r = -0.11, p = 0.0038 for EDV, r = -0.16, p < 0.0001 for the pulse wave analysis and r = 0.01, p = 0.65 for FMD). Neither LDL-cholesterol, nor non-HDL-cholesterol, was significantly related to the measurements of endothelium-dependent vasodilation. Also endothelium-independent vasodilation (EIDV) evaluated by the invasive forearm technique with sodium nitroprusside was related to apoB/A1 levels (r = -0.12, p < 0.0016). Conclusion: The apoB/A1 levels, but not LDL-cholesterol, were inversely related to endothelium-dependent vasodilation evaluated by EDV and pulse wave analysis, but not by FMD. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with high apoB/A1 levels.

  • 36.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Andersson, Jessika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gustavsson, Tomas
    The echogenecity of the intima-media complex in the common carotid artery is closely related to the echogenecity in plaques.2007Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 195, nr 2, s. 411-414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    The echogenecity measured by ultrasound of atherosclerotic plaques is related to future cardiovascular events. The aim of the present study is to relate the grey scale median of the intima–media complex (IM-GSM) of the common carotid artery (CCA) to the echogenecity of carotid plaques.

    Material and results

    In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, carotid artery intima–media thickness (IMT) and IM-GSM were evaluated by ultrasound and computerized analysis. Also the occurrence of plaque and plaque GSM were measured. The echogenecity of the plaques was also visually estimated by the Gray-Weale classification.

    In subjects with a carotid plaque (n=582), IM-GSM in CCA was correlated to GSM in the plaque (r=0.60, p<0.0001) independently of plaque size and IMT. IM-GSM in CCA was also correlated to the visually estimated echogenecity (p<0.0001 for trend).

    Conclusion

    IM-GSM of the CCA is closely related to the echogenecity in overt carotid plaques, regardless if evaluated by the same computerized method or evaluated visually. This finding suggests that IM-GSM of CCA could be an important and easily measurable characteristic of the carotid artery wall that could be obtained in almost all subjects and not only those with an overt plaque.

  • 37.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Hulthe, Johannes
    von Below, Catrin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Vasodilation and visceral fat in elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2007Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 194, nr 2, s. e64-e71Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although obesity has long been recognised as a cardiovascular risk factor, only in recent years has the role of visceral adipose tissue (VAT) been evaluated. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we related VAT and other obesity indices to endothelium-dependent vasodilation in both capacitance and resistance arteries. METHODS AND RESULTS: In this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Intra-abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were determined by magnetic resonance imaging in a random sample of 287 subjects. EDV, but not FMD, was inversely related to VAT, SAT, BMI and the waist/hip ratio (r=-0.23, -0.16, -0.21 and -0.11, respectively, p=0.05-0.001 after adjustment for gender). In multiple regression analysis however, only VAT was an independent predictor of EDV. Similar results were obtained for endothelium-independent vasodilation (EIDV, infusion of sodium nitroprusside in the brachial artery). CONCLUSIONS: Both endothelium-dependent and independent vasodilation in the forearm resistance arteries, but not FMD in the brachial artery, was reduced in elderly subjects with increased intra-abdominal adipose tissue mass. This finding suggests deterioration in general vasoreactivity mainly in resistance arteries in elderly subjects with intra-abdominal obesity.

  • 38.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Teerlink, Tom
    Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
    L-Arginine is related to endothelium-dependent vasodilation in resistance and conduit arteries in divergent ways-The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Atherosclerosis, Vol. 203, nr 2, s. 544-549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the conversion of l-arginine to the endothelium-derived vasodilator nitric oxide. We evaluated if circulating levels of l-arginine and ADMA, and the ratio thereof, were related to endothelium-dependent vasodilation in both resistance and conductance arteries in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS AND RESULTS: In this population-based study, vascular function of 1016 subjects aged 70 was evaluated by the invasive forearm technique with intra-brachial infusion of acetylcholine (EDV), by measurement of flow-mediated dilation (FMD) of the brachial artery, and by change in reflectance index (RI) by pulse wave analysis. After adjustment for resting forearm blood flow, gender, Framingham risk score, and glomerular filtration rate, the l-arginine/ADMA ratio was positively related to EDV (P=0.005). This association was mainly driven by l-arginine, because if both l-arginine and ADMA were entered as predictor variables in a single regression model, l-arginine was positively associated with EDV (P=0.001), whereas the negative association between ADMA and EDV was not significant. In contrast, after adjustment for baseline brachial diameter, gender, Framingham risk score, and glomerular filtration rate, the l-arginine/ADMA ratio was negatively related to FMD (P=0.004). Again, this association was mainly driven by l-arginine (P=0.002), whereas ADMA was not significantly related to FMD. The change in RI was not related to l-arginine, ADMA or their ratio. CONCLUSIONS: In elderly subjects the l-arginine/ADMA ratio and l-arginine, but not ADMA, are positively related to endothelium-dependent vasodilation in resistance arteries, but negatively in a conduit artery.

  • 39.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Hulthe, Johannes
    Elmgren, Anders
    C-reactive protein and e-selectin levels are related to vasodilation in resistance, but not conductance arteries in the elderly: the prospective investigation of the Vasculature in Uppsala Seniors (PIVUS) study2008Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 199, nr 1, s. 129-137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Divergent results have emerged in the past when relating single markers of inflammation to measures of vascular reactivity. The aim of the present study is to relate a wide range of inflammatory markers to vasoreactivity in both resistance and conductance arteries. METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (the PIVUS study), endothelium-dependent vasodilation was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery (EDV), the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD) and the pulse wave analysis method with beta-2 receptor agonist (terbutaline) provocation in 1016 subjects aged 70. A panel of 14 inflammatory markers, including cytokines, chemokines, adhesion molecules, CRP, sCD40 ligand and leukocyte count, was measured. RESULTS: After adjustment for gender and coronary risk factors, EDV was independently related to CRP levels and e-selectin in an inverse way (p<0.006 for both). FMD was not significantly related to any marker of inflammation after adjustment. Endothelium-independent vasodilation evaluated by the invasive forearm technique with sodium nitroprusside was also found to be related to both CRP and e-selectin in an inverse way (p=0.005 and p=0.045, respectively). CONCLUSION: Acetylcholine-induced vasodilation in the forearm, but not FMD, was inversely related to CRP and e-selectin levels independently of traditional risk factors in elderly subjects. As also endothelium-independent vasodilation was related to CRP and e-selectin, general vasoreactivity in resistance arteries seems to be effected by low-grade inflammation in elderly subjects.

  • 40.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindahl, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis2015Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 242, nr 1, s. 205-210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: We used a proteomics array to simultaneously measure multiple proteins that have been suggested to be associated with atherosclerosis and related them to plaque prevalence in carotid arteries in a human population-based study. Methods: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS; n = 931, 50% women, all aged 70 years), the number of carotid arteries with plaques was recorded by ultrasound. Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink Bioscience, Uppsala, Sweden) and related to carotid measures in a regression framework. Results: Following adjustment for multiple testing with Bonferroni correction, seven of the proteins were significantly related to the number of carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.13-1.49 per standard deviation increase), growth hormone (OR, 1.24; 95% CI, 1.08-1.43), osteoprotegerin (OR, 1.22; 95% CI, 1.05-1.43) and TNFSF14 (OR, 1.17; 95% CI, 1.01-1.35) were related to plaque prevalence independently of each other and traditional cardiovascular risk factors. Conclusion: A novel targeted proteomics approach using the proximity extension technique discovered several new associations of candidate proteins with carotid artery plaque prevalence in a large human sample.

  • 41.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating levels of bisphenol A and phthalates are related to carotid atherosclerosis in the elderly2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, nr 1, s. 207-213Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: Bisphenol A (BPA) levels have previously been associated with coronary heart disease (CHD). Since CHD is an atherosclerotic disease, we investigated if circulating levels of BPA and phthalate metabolites are related to atherosclerosis in a cross-sectional study. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), the prevalence of overt plaques and echogenectity (grey scale median, GSM) of carotid artery plaques were recorded by ultrasound in both of the carotid arteries. The thickness (IMT) and echogenicity (IM-GSM) of the intima-media complex were also measured. Bisphenol A (BPA) and 10 phthalate metabolites were analyzed in serum by a API 4000 liquid chromatograph/tandem mass spectrometer. Results: Mono-methyl phthalate (MMP) was related to carotid plaques in an inverted U-shaped manner. This pattern was significant after adjustment for gender, body mass index, blood glucose, blood pressure, HDL and LDL-cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use (p = 0.004). High levels of BPA, mono-isobutyl phthalate (MiBP) and MMP were associated with an echogenic IM-GSM and plaque GSM, while high levels of mono-2-ethylhexyl phthalate (MEHP) were associated with an echolucent IM-GSM and plaque GSM (p < 0.0001 after adjustment). Conclusion: The phthalate metabolite MMP was related to atherosclerotic plaques in an inverted U-shaped manner independently of CV risk factors. Some phthalates and BPA were also related to the echogenicity of the plaques, suggesting a role for plaque-associated chemicals in atherosclerosis.

  • 42.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Van Bavel, Bert
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    The changes in plasma levels of perfluoroalkyl substances (PFASs) are related to the increase in carotid intima-media thickness over 10 years2017Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, s. E18-E18Artikel i tidskrift (Övrigt vetenskapligt)
  • 43.
    Lundberg, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ebeling Barbier, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Hansen, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Total atherosclerotic burden by whole body magnetic resonance angiography predicts major adverse cardiovascular events2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, nr 1, s. 148-152Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    The purpose of the present study was to investigate the relationship between the Total Atherosclerotic Score (TAS), a measurement of the overall atherosclerotic burden of the arterial tree by whole body magnetic resonance angiography (WBMRA), and the risk of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, stroke and/or coronary revascularization, assuming that TAS predicts MACE.

    METHODS AND RESULTS:

    305 randomly selected 70 year-old subjects (47% women) underwent WBMRA. Their atherosclerotic burden was evaluated and TAS > 0, that is atherosclerotic changes, were found in 68% of subjects. During follow-up (mean 4.8 years), MACE occurred in 25 subjects (8.2%). Adjusting for multiple risk factors, TAS was associated with MACE (OR 8.86 for any degree of vessel lumen abnormality, 95%CI 1.14-69.11, p = 0.037). In addition, TAS improved discrimination and reclassification when added to the Framingham risk score (FRS), and ROC (Receiver Operator Curve) increased from 0.681 to 0.750 (p = 0.0421).

    CONCLUSION:

    In a population-based sample of 70 year old men and women WBMRA, with TAS, predicted MACE independently of major cardiovascular risk factors.

  • 44.
    Mirza, Majd A I
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Tobias E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 205, nr 2, s. 385-390Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Subjects with chronic kidney disease (CKD) are at higher risk for cardiovascular (CV) disease than the general population. These patients have elevated circulating levels of FGF23, which predict for increased mortality in CKD patients on hemodialysis. Since CV disease is a major cause of death in CKD, we investigated the association between FGF23 and vascular function. METHODS AND RESULTS: We employed a community-based cohort of subjects aged 70, the PIVUS study (n=967), to investigate the relation between serum FGF23, endothelium function and arterial stiffness. Higher FGF23 was weakly associated with both impaired endothelium-dependent (beta=-0.08, p<0.05) and endothelium-independent (beta=-0.08, p<0.01) vasodilation. The association was stronger in subjects with eGFR> or =90mL/min/1.73m(2) (beta=-0.19 and beta=-0.22, respectively, p<0.001). In addition, higher FGF23 was associated with increased arterial stiffness exclusively in subjects with an age-adjusted impaired renal function (eGFR<60mL/min/1.73m(2)) (beta=0.26, p<0.001). All associations were independent of gender, biochemical covariates and established CV risk factors. CONCLUSIONS: Higher serum FGF23 levels, even within the normal range, are independently associated with impaired vasoreactivity and increased arterial stiffness in the community. Additional studies are required to determine possible direct vascular effects of FGF23 and whether FGF23 is a modifiable CV risk factor.

  • 45.
    Mirza, Majd A. I.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Tobias E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 207, nr 2, s. 546-551Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fibroblast growth factor-23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Serum FGF23 is elevated in chronic kidney disease (CKD) and is a prognostic marker of poor outcomes, such as faster CKD progression and increased mortality in hemodialysis patients. Despite the high prevalence of cardiovascular disease in CKD, the relation between circulating FGF23 and cardiovascular risk factors, both in CKD and in the community, has not been studied in detail. We evaluated the relation between FGF23, left ventricular mass index (LVMI), hypertrophy (LVH) and LV geometry, employing the community-based PIVUS cohort. In total, 795 Swedish men and women aged 70 were included of which 164 had an age-adjusted diminished renal function (estimated glomerular filtration rate<60mL/min/1.73m(2)). FGF23 was positively associated with LVMI (beta=0.11, CI 0.01-0.18), with increased odds for the presence of LVH (OR 1.28, CI 1.09-1.51) and for concentric hypertrophy (OR 1.45, CI 1.19-1.77) in the whole population. All associations were stronger in subjects with eGFR<60mL/min/1.73m(2) (beta=0.30, CI 0.15-0.46 for LVMI; OR 1.86, CI 1.30-2.67 for the presence of LVH; OR 1.83, CI 1.17-2.85 and OR 1.87, CI 1.08-3.22 for concentric and eccentric hypertrophy, respectively). The results were essentially unaltered in multivariate models. In summary, elevated serum FGF23 levels, even within the normal range, are associated with increased LVMI and increased risk for the presence of LVH in elderly subjects. Additional longitudinal studies that evaluate the predictive power of FGF23 and whether FGF23 has additional clinical applications are needed.

  • 46.
    Naessen, Tord
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Rodriguez-Macias, Kenny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Menopausal estrogen therapy counteracts normal aging effects on intima thickness, media thickness and intima/media ratio in carotid and femoral arteries: An investigation using noninvasive high-frequency ultrasound2006Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 189, nr 2, s. 387-392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Estrogen therapy that is started at the time of menopause seems to protect against the development of atherosclerosis and cardiovascular diseases, in contrast to the initial increased cardiovascular risk when hormone therapy is initiated in older women. With increased aging and degree of atherosclerosis, the thickness of the artery intima increases and that of the media decreases. These changes can be noninvasively estimated using high-frequency ultrasound.

    Methods and results: The thickness of carotid and femoral artery intima and media was assessed, using noninvasive high-frequency ultrasound (25 MHz). Long-term estrogen users (mean treatment duration 20 years) had a significantly thinner mean carotid intima layer (-25%; P=0.0002), a thicker media layer (+74%; P=0.0002) and a substantially lower intima/media thickness ratio (-54%; P < 0.0001) than 17 age-matched nonusers, with values closer to those in 20 premenopausal women. Similar but less pronounced differences between the postmenopausal groups were found for the femoral artery.

    Conclusions: A preserved thin artery wall intima and a low intima/media thickness ratio, at values close to those in young women might be partially responsible for the beneficial cardiovascular effects of estrogen therapy when it is initiated at the time of menopause.

  • 47.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Jobs, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Association between glomerular filtration rate and endothelial function in an elderly community cohort2012Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, nr 1, s. 242-246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

    METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

    RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

    CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

  • 48. Ohrvall, M
    et al.
    Berglund, L
    Salminen, I
    Lithell, H
    Aro, A
    Vessby, B
    The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up.1996Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 127, nr 1, s. 65-71Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970-1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970-1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL/HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced delta 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

  • 49.
    Ostman, Maja Eriksson
    et al.
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Calais, Fredrik
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Rosenblad, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Leppert, Jerzy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hedberg, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Vastmanland Cty Hosp, Dept Clin Physiol, Vasteras, Sweden.
    Prognostic impact of subclinical or manifest extracoronary artery diseases after acute myocardial infarction2017Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, s. 53-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: In patients with coronary artery disease (CAD), clinically overt extracoronary artery diseases (ECADs), including claudication or previous strokes, are associated with poor outcomes. Subclinical ECADs detected by screening are common among such patients. We aimed to evaluate the prognostic impact of subclinical versus symptomatic ECADs in patients with acute myocardial infarction (AMI). Methods: In a prospective observational study, 654 consecutive patients diagnosed with AMI underwent ankle brachial index (ABI) measurements and ultrasonographic screening of the carotid arteries and abdominal aorta. Clinical ECADs were defined as prior strokes, claudication, or extracoronary artery intervention. Subclinical ECADs were defined as the absence of a clinical ECAD in combination with an ABI <= 0.9 or >1.4, carotid artery stenosis, or an abdominal aortic aneurysm. Results: At baseline, subclinical and clinical ECADs were prevalent in 21.6% and 14.4% of the patients, respectively. Patients with ECADs received evidence-based medication more often at admission but similar medications at discharge compared with patients without ECADs. During a median follow-up of 5.2 years, 166 patients experienced endpoints of hospitalization for AMI, heart failure, stroke, or cardiovascular death. With ECAD-free cases as reference and after adjustment for risk factors, a clinical ECAD (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.34-3.27, p = 0.001), but not a subclinical ECAD (HR 1.35, 95% CI 0.89-2.05, p = 0.164), was significantly associated with worse outcomes. Conclusions: Despite receiving similar evidence-based medication at discharge, patients with clinical ECAD, but not patients with a subclinical ECAD, had worse long-term prognosis than patients without an ECAD after AMI.

  • 50. Paniagua, J. A.
    et al.
    Perez-Martinez, P.
    Gjelstad, Ingrid M. F.
    Tierney, Audrey C.
    Delgado-Lista, J.
    Defoort, Catherine
    Blaak, Ellen E.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Drevon, Christian A.
    Kiec-Wilk, Beata
    Lovegrove, Julie A.
    Roche, Helen M.
    Lopez-Miranda, J.
    A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, nr 2, s. 443-450Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project. Methods and design: Clinical intervention study: the patients (n = 337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). Measurements: the effects on MetS risk criteria were recorded before and after the intervention period. Results: An enlarged waist circumference (>= 88 cm for women and >= 102 cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85 mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (>= 5.55 mmol/L), 51% were hypertriacylglycerolemic (>= 1.7 mmol/L), and 72% had low HDL cholesterol (<1.0 mmol/L for men, and <1.3 mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p<0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p<0.028). Conclusions: The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets. 

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