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  • 1. Andren, Ann
    et al.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Walker-Engström, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wahlen, Petra
    Tegelberg, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Effects of treatment with oral appliance on 24-h blood pressure in patients with obstructive sleep apnea and hypertension: a randomized clinical trial2013In: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709, Vol. 17, no 2, p. 705-712Article in journal (Refereed)
    Abstract [en]

    Continuous positive airway pressure treatment has been shown to lower blood pressure (BP) in patients with obstructive sleep apnea (OSA). The aims of the present pilot study were to evaluate the potential effects of oral appliance (OA) therapy on BP, to assess various outcome BP measures, and to inform sample size calculation. Seventy-two patients with OSA and hypertension were randomly assigned to intervention with either an OA with mandibular advancement (active group) or an OA without advancement (control group). Before and after 3 months of treatment, the patients underwent nocturnal somnographic registration and 24-h ambulatory BP monitoring. Among the various BP measures, the largest trend toward effect of OA treatment was seen in 24-h mean systolic BP with a 1.8 mmHg stronger BP reduction in the active group compared with controls. A stronger trend toward effect was seen in a subgroup with baseline ambulatory daytime mean systolic BP > 135/85 mmHg where the mean systolic BP fell, on average, 2.6 mmHg. Additional exclusion of patients with baseline apnea hypopnea index (AHI) a parts per thousand currency sign15 gave a significant reduction in mean systolic BP of 4.4 mmHg (P = 0.044) in the active group compared with controls. In patients with OSA and hypertension, OA treatment had a modest trend toward effect on reducing BP. A stronger trend toward treatment effect was seen after excluding patients with normal baseline ambulatory BP. Additional exclusion of patients with baseline AHI a parts per thousand currency sign15 showed a significant treatment effect. Data to inform sample size for an adequately powered randomized study are provided.

  • 2. Calais, Fredrik
    et al.
    Frobert, Ole
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wachtell, Kristian
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leisure-time Physical Inactivity and Risk of Myocardial Infarction and All-cause Mortality: a Case-control Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 3. Calais, Fredrik
    et al.
    Frobert, Ole
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wachtell, Kristian
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leisure-time physical inactivity and risk of myocardial infarction and all-cause mortality: A case-control study2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 2, p. 599-600Article in journal (Refereed)
  • 4.
    Calais, Fredrik
    et al.
    Örebro Univ, Fac Hlth, Dept Cardiol, Örebro, Sweden.
    Ostman, Maja Eriksson
    Örebro Univ, Fac Hlth, Dept Cardiol, Örebro, Sweden.
    Hedberg, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Karlsson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Fröbert, Ole
    Örebro Univ, Fac Hlth, Dept Cardiol, Örebro, Sweden.
    Incremental prognostic value of coronary and systemic atherosclerosis after myocardial infarction2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 261, p. 6-11Article in journal (Refereed)
    Abstract [en]

    Background: The role of systemic atherosclerosis in myocardial infarction (MI) patients is not fully understood. We investigated the incremental prognostic value of coronary and systemic atherosclerosis after acute MI by estimating extra-cardiac artery disease (ECAD) and extent of coronary atherosclerosis.

    Methods and results: The study included 544 prospective MI patients undergoing coronary angiography. For all patients, the longitudinal coronary atherosclerotic extent, expressed as Sullivan extent score (SES) was calculated. In addition, the patients underwent non-invasive screening for ECAD in the carotid, aortic, renal and lower limb. SES was found to be associated with ECAD independent of baseline clinical parameters [adjusted odds ratio (OR) 1.04 95% confidence interval (CI) 1.02–1.06, P < 0.001]. Extensive systemic atherosclerosis, defined as the combination of extensive coronary disease (SES ≥ 17) and ECAD, was associated with higher risk for all-cause mortality compared to limited systemic atherosclerosis (SES < 17 and no ECAD) (hazard ratio [HR] 2.9 95% CI 1.9–4.5, P < 0.001, adjusted for Global Registry of Acute Coronary Events risk score parameters 1.8, 95% CI 1.1–3.0, P = 0.019). The risk for the composite endpoint of cardiovascular death or hospitalization was significantly higher in patients with extensive systemic atherosclerosis compared to patients with limited systemic atherosclerosis (HR 3.1, 95% CI 2.1–4.7, P < 0.001, adjusted HR 1.9, 95% CI 1.2–3.1, P < 0.004).

    Conclusions: Visual estimation of the longitudinal coronary atherosclerotic extent at the time of MI predicts ECAD. Coexistence of extensive coronary disease and ECAD defines a group with particularly poor prognosis after MI.

  • 5.
    Calais, Fredrik
    et al.
    Orebro Univ, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden.
    Ostman, Maja Eriksson
    Orebro Univ, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Karlsson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Fröbert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden.
    Reply to "Letter to editor, Assessing the effect of coronary and systemic atherosclerosis following myocardial infarction" by dr Su Yueqiu et al.2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 271, p. 29-29Article in journal (Other academic)
  • 6.
    Doerstling, Steven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 86-93Article in journal (Refereed)
    Abstract [en]

    Background: Despite the growing body of evidence on growth differentiation factor 15 (GDF-15) reference values for patients with existing cardiovascular disease, limited investigation has been dedicated to characterizing the distribution and prognostic impact of GDF-15 in predominantly healthy populations. Furthermore, current cutoff values for GDF-15 fail to account for the well-documented age-dependence of circulating GDF-15. Methods: From 810 community-dwelling older adults, we selected a group of apparently healthy participants (n = 268). From this sample, circulating GDF-15 was modeled using the generalized additive models for location scale and shape (GAMLSS) to develop age-dependent centile values. Unadjusted and adjusted Cox proportional hazards models were used to assess the association between the derived GDF-15 reference values (expressed as centiles) and all-cause mortality. Results: Smoothed centile curves showed increasing GDF-15 with age in the apparently healthy participants. An approximately three-fold difference was observed between the 95th and 5th GDF-15 centiles across ages. In a median 8.0 years of follow-up, 97 all-cause deaths were observed in 806 participants with eligible values. In unadjusted Cox regression analyses, the hazard ratio (95% CI) for all-cause mortality per 25-unit increase in GDF-15 centile was 1.80 (1.48-2.20) and dichotomized at the 95th centile, >= 95th versus <95th, was 3.04 (1.99-4.65). Age-dependent GDF-15 centiles remained a significant predictor of all-cause mortality in all subsequent adjusted models. Conclusions: Age-dependent GDF-15 centile values developed from a population of apparently healthy older adults are independently predictive of all-cause mortality. Therefore, GDF-15 reference values could be a useful tool for risk-stratification in a clinical setting.

  • 7.
    Hedberg, Par
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, S-72189 Vasteras, Sweden..
    Selmeryd, Jonas
    Vastmanland Cty Hosp, Dept Clin Physiol, S-72189 Vasteras, Sweden..
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Vastmanland Cty Hosp, Dept Clin Physiol, S-72189 Vasteras, Sweden..
    Left atrial minimum volume is more strongly associated with N-terminal pro-B-type natriuretic peptide than the left atrial maximum volume in a community-based sample2016In: International Journal of Cardiac Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 32, no 3, p. 417-425Article in journal (Refereed)
    Abstract [en]

    Previous data have demonstrated that left atrial (LA) minimum volume indexed for body surface area (LAVImin) is more strongly associated with the Doppler echocardiographic E/e' ratio than LA maximum volume index (LAVImax). We sought to explore if LAVImin was more closely related to serum levels of NT-proBNP than LAVImax and E/e' in the community. A community-based sample of 730 subjects underwent echocardiographic examinations and NT-proBNP measurements. The mean age of the participants was 66.3 years (range 38-86) and 72 % were men. Age (Spearman correlation [rho] 0.533), LAVImin (rho 0.460), LAVImax (rho 0.360), estimated glomerular filtration rate (rho -0.349), and E/e' (rho 0.301; all P < 0.001) were strongly correlated with log-NT-proBNP. In a multiple linear regression model with log-NT-proBNP as dependent variable and LAVImin, LAVImax, E/e' ratio, and potential confounders as predictors, an adjusted R-2 of 44.9 % was obtained. When excluding either of LAVImin (R-2 42.6 %, P < 0.001) or E/e' (R-2 44.6 %, P = 0.019) the model fit was significantly reduced. In contrast, when LAVImax was excluded the model fit was preserved (R-2 45.0 %, P = 0.69). To detect an NT-proBNP level of > 125 ng/L, LAVImin yielded a significantly larger area under the receiver operating characteristic curve (AUC) of 0.749 than LAVImax (AUC 0.701; P < 0.001) and E/e' (AUC 0.661; P < 0.001). In our community-based sample, LAVImin was more strongly associated with NT-proBNP than LAVImax. Moreover, the discriminatory power to detect an elevated NT-proBNP level was stronger in LAVImin than in LAVImax and E/e'. Our findings support previous data that LAVImin may be more closely related to LV filling function than LAVImax.

  • 8.
    Hedberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hammar, Charlotta
    Selmeryd, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Viklund, Josefin
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hellberg, Anders
    Henriksen, Egil
    Left ventricular systolic dysfunction in outpatients with peripheral atherosclerotic vascular disease: prevalence and association with location of arterial disease2014In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 16, no 6, p. 625-632Article in journal (Refereed)
    Abstract [en]

    Aims: We aimed to determine the prevalence of left ventricular systolic dysfunction (LVSD) in outpatients with peripheral atherosclerotic vascular disease (PAVD). Further, the associations of stenotic internal carotid artery disease (SICAD) and lower extremity artery disease (LEAD) with LVSD were evaluated.

    Methods and results: In the Peripheral Artery Disease in Vastmanland study, consecutive outpatients with ultrasonographically identified mild to severe stenosis in the internal carotid artery or symptoms of claudication combined with either ankle brachial index of 0.90 or ultrasonographic occlusive findings were included (n=437). Population-based control subjects were matched to the patients (n=395). LVSD was defined as echocardiographically determined left ventricular ejection fraction (LVEF) <55%, and moderate or greater LVSD was defined as LVEF <45%. The prevalence of LVSD was significantly greater in patients than in controls (13.7% vs. 6.1%, P<0.001). The prevalence of moderate or greater LVSD in participants not on treatment with a combination of angiotensin-converting enzyme inhibitor and beta-blocker was 2.3% in patients and 1.3% in controls (P=0.31). When LEAD and SICAD were analysed together, adjusted for potential confounders, SICAD [odds ratio (OR) 2.54, 95% confidence interval (CI) 1.03-6.32], but not LEAD (OR 1.59, 95% CI 0.80-3.18), was independently associated with LVSD.

    Conclusions: In outpatients with PAVD, we found a 13.7% prevalence of LVSD. However, the prevalence of at least moderate LVSD in patients not on treatment with angiotensin-converting enzyme inhibitor and a beta-blocker was only 2.3% and not significantly different from controls. Stenotic artery disease in the internal carotid artery, but not in the lower extremities, was independently associated with LVSD.

  • 9.
    Hedberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Jonason, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lönnberg, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Göran
    Pehrsson, Kenneth
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Mitral annulus motion compared with wall motion scoring index in the assessment of left ventricular ejection fraction2003In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 16, no 6, p. 622-629Article in journal (Refereed)
    Abstract [en]

    The biplane disc summation method is the recommended echocardiographic procedure to determine left ventricular (LV) ejection fraction (EF). Assessment of mitral annulus motion (MAM) or wall motion scoring index (WMI) has been reported to be less dependent on image quality compared with the recommended method, and proposed as a surrogate to the disc summation method in calculation of LVEF. We aimed to compare MAM and WMI in the echocardiographic assessment of LVEF. In a randomly selected population-based sample of 75-year-old men and women in sinus rhythm (n = 409) MAM, as measured by M-mode, was compared with WMI, calculated as the mean value of wall motion scoring in 9 LV segments. LVEF, as measured by the biplane disc summation method was used as reference. The limits of agreement (mean difference ± 1.96 SD) between LVEF and corresponding MAM values were −18 to +13 LVEF%, and between LVEF and corresponding WMI values were −12 to +13 LVEF%. The areas under the receiver operating characteristic curves for MAM and WMI to predict a LVEF < 50% were 0.892 and 0.998, respectively (95% confidence interval of the difference 0.062-0.149). The corresponding areas for MAM and WMI to predict a LVEF < 40% were 0.955 and 0.998, respectively (95% confidence interval of the difference 0.017-0.069). In conclusion, the ability of WMI to estimate LVEF was more favorable than MAM in this population-based sample of 75-year-old participants. The findings suggest that the WMI is preferable to MAM in estimating LVEF.

  • 10. Hedberg, Pär
    et al.
    Lönnberg, Ingemar
    Jonason, Tommy
    Nilsson, Göran
    Pehrsson, Kenneth
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Electrocardiogram and B-type natriuretic peptide as screening tools for left ventricular systolic dysfunction in a population-based sample of 75-year-old men and women2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 3, p. 524-529Article in journal (Refereed)
    Abstract [en]

    Background: Plasma concentration of B-type natriuretic peptide (BNP) has been suggested as a powerful screening tool for left ventricular systolic dysfunction. However, there are reports indicating that the 12-lead electrocardiogram (ECG) could be just as powerful. We aimed to evaluate the 12-lead ECG and BNP as screening tools for left ventricular systolic dysfunction in an elderly, unselected population.

    Methods: In a randomly selected population-based sample of 75-year-old men and women (n = 407), diagnostic characteristics were evaluated for the ECG and plasma concentration of BNP to detect left ventricular systolic dysfunction.

    Results: Sensitivity, specificity, and negative and positive predictive values for the ECG to detect left ventricular systolic dysfunction were 96%, 79%, 100%, and 26%, respectively. The corresponding values for the BNP (cut-off value 28 pg/mL) were 93%, 55%, 99%, and 13%. In participants without major abnormalities in the ECG, left ventricular systolic dysfunction was found in <1% (1/302), irrespective of BNP concentrations. In participants with abnormal ECGs, systolic dysfunction was more prevalent in persons with abnormal BNP concentrations than in those with normal concentrations (35% vs 3%, difference 32%, 95%CI for the difference 16%–44%)

    Conclusions: In 75-year-old subjects both the ECG and the plasma concentration of BNP are highly efficient in excluding left ventricular systolic dysfunction. However, compared with the BNP, the ECG yields a lower number of false positive cases. In screening for left ventricular systolic dysfunction, the BNP has a diagnostic value in addition to the ECG, but only in individuals with abnormal ECGs.

  • 11. Hedberg, Pär
    et al.
    Lönnberg, Ingemar
    Jonason, Tommy
    Nilsson, Göran
    Pehrsson, Kenneth
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Left ventricular systolic dysfunction in 75-year-old men and women: A population-based study2001In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 22, no 8, p. 676-683Article in journal (Refereed)
    Abstract [en]

    Aims To determine the prevalence of left ventricular systolic dysfunction in 75-year-old men and women.

    Methods and Results In a population-based random sample of 75-year-old subjects (n = 433; response rate 70.1%) the left ventricular systolic function was determined using two echocardiographic methods: (1) wall motion in nine left ventricular segments was visually scored and wall motion index was calculated as the mean value of the nine segments and (2) ejection fraction as measured by the disc summation method. Presence of heart failure was determined by a cardiologist's clinical evaluation. Wall motion index was achievable in 95% of the participants while ejection fraction was measurable in 65%. Normal values were obtained from a healthy subgroup (n = 108) and left ventricular systolic dysfunction was defined as the 0.5th percentile of the wall motion index (i.e. <1.7). In participants in whom both ejection fraction and wall motion index were achievable, wall motion index <1.7 predicted ejection fraction <43% with a sensitivity and specificity of 84.0% and 99.6%, respectively. The prevalence of left ventricular systolic dysfunction was 6.8% (95% CI, 5.6-8.0%) and was greater in men than in women (10.2% vs 3.4%, P = 0.006). Clinical evidence of heart failure was absent in 46% of the participants with left ventricular systolic dysfunction.

    Conclusions Left ventricular systolic dysfunction is common among 75-year-olds with a prevalence of 6.8% in our estimate. The condition is more likely to affect men than women. In nearly half of 75-year-olds with left ventricular systolic dysfunction there is no clinical evidence of heart failure.

  • 12.
    Hedberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Magounakis, Theo
    Dubaniewicz, Witek
    Viklund, Josefin
    Carlsson, Jörg
    "Brustet hjärta" eller takotsubo-kardiomyopati drabbar kvinnor i postmenopaus. Stressutlöst tillstånd som linkar akut hjärtinfarkt: ["Broken heart" or Takotsubo cardiomyopathy mostly in postmenopausal women. Stress-induced condition resembling acute myocardial infarction]2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 44, p. 3277-3282Article in journal (Other academic)
    Abstract [en]

    Transient left ventricular dysfunction in patients under emotional or physiological stress, also known as takotsubo-cardiomyopathy, has recently been recognised as a distinct clinical entity. The syndrome is characterised by an onset resembling acute myocardial infarction and reversible wall motion abnormalities involving the left ventricular apex and mid-ventricle, but without angiographic evidence of coronary artery stenosis. In this report we present two cases and review the clinical characteristics and potential pathophysiological mechanisms of the takotsubo-cardiomyopathy.

  • 13.
    Hedberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden..
    Selmeryd, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden..
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden..
    Long-term prognostic impact of left atrial volumes and emptying fraction in a community-based cohort2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 9, p. 687-693Article in journal (Refereed)
    Abstract [en]

    Objective: We hypothesised that left atrial emptying fraction (LAEF) would predict long-term cardiovascular outcome in the general population and better so than left atrial (LA) volumes.

    Methods: A community-based sample (n=740) in sinus rhythm prospectively underwent clinical evaluation, echocardiography and blood analyses including N terminal pro B-type natriuretic peptide (NTproBNP). The LA maximum (LAVmax) and minimum volumes (LAVmin) were indexed to body surface area (LAVImax and LAVImin, respectively). LAEF was calculated as LAVmaxLAVmin divided by LAVmax. The participants were followed for a median of 4.9 years regarding incident cardiovascular events (cardiovascular death or hospitalisation because of myocardial infarction, heart failure or stroke). Cox regression models were used to evaluate the associations of LA volumes and LAEF with the outcome.

    Results: In a multivariable beta regression model, including clinical and echocardiographic baseline characteristics, higher plasma levels of NTproBNP, higher E/e' and left ventricular systolic dysfunction remained as independent determinants of a lower LAEF. After adjustment for baseline characteristics, including NTproBNP levels, LAEF (HR for 1 SD decrease 1.33, 95% CI 1.04 to 1.70, p=0.022), but not LAVImax (HR for 1 SD increase 0.88, 95% CI 0.70 to 1.10, p=0.25) or LAVImin (HR for 1 SD increase 1.02, 95% CI 0.83 to 1.27, p=0.83) remained independently associated with outcome.

    Conclusions: In this community-based cohort, LAEF was a powerful predictor of incident cardiovascular events and its predictive ability was stronger than for LA volumes. Our findings suggest that LA dysfunction may represent a more advanced state of LA remodelling than LA enlargement.

  • 14.
    Henriksen, Egil
    et al.
    Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Selmeryd, Jonas
    Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Associations of left atrial volumes and Doppler filling indices with left atrial function in acute myocardial infarction2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 1, p. 85-92Article in journal (Refereed)
    Abstract [en]

    Recent findings suggest that left atrial (LA) function is more strongly related to adverse prognosis than LA volumes. We aimed to evaluate the associations between LA volumes and Doppler filling indices with LA function. Echocardiographic LA volumes (LAVs), mitral valve early (MV-E) and late (MV-A) peak flow velocities, and mitral atrioventricular plane tissue-Doppler early (TD-e ') and late (TD-a ') peak velocities were obtained in 320 patients with acute myocardial infarction (AMI) free from atrial fibrillation and more than moderate valvular disease. LA function was estimated as the LA emptying fraction (LAEF), that is 100x (LAVmax-LAVmin)/LAVmax. LA reservoir volume was calculated as LAVmax-LAVmin and LA transit volume as LV stroke volume-reservoir volume. In restricted cubic spline regression analyses with multivariable adjustment, a reduced LAEF was strongly associated with smaller reservoir volume, larger transit volume, LAVmax, LAVpreA and especially LAVmin. MV-E linearly increased with a lower LAEF, whereas MV-A decreased but only below LAEF levels of approximately 45%. The resulting E/A ratio showed a sudden increase in LAEF levels below similar to 45%. Lower TD-a ' was linearly associated with a lower LAEF. In conclusion, a reduced atrial function was associated with smaller LA reservoir volume, larger LA transit volume, lower TD-a ', a non-linear decrease in MV-A and a non-linear increase in E/A. Our findings are likely a reflection of the adaptation to sustain LV filling volume and counteracting a rise in pulmonary venous pressure in face of an enhanced LV end-diastolic pressure.

  • 15. Henriksen, Egil
    et al.
    Selmeryd, Jonas
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Echocardiographic assessment of maximum and minimum left atrial volumes: a population-based study of middle-aged and older subjects without apparent cardiovascular disease2015In: International Journal of Cardiac Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 31, no 1, p. 57-64Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to obtain reference values of maximum and minimum left atrial volumes (maxLAV and minLAV, respectively) in a population-based subset without apparent cardiovascular disease or other factors potentially associated with left atrial enlargement. Because left ventricular diastolic dysfunction is commonly found in elderly subjects, we also tried to identify the presence of possible preclinical diastolic dysfunction in the study population. A population-based sample of 168 subjects (127 men and 41 women) underwent two-dimensional echocardiography using the single-plane disc method to determine maxLAV and minLAV. maxLAV and minLAV were indexed to body surface area (maxLAVi and minLAVi, respectively). maxLAVi was independent of age and sex, and produced reference limits (mean +/- A 1.96 SD) of 15-37 mL/m(2). minLAVi was correlated with age, and produced estimated reference limits of 3-15 and 7-23 mL/m(2) in 40- and 80-year-old subjects, respectively. Based on the age-dependent reference values from the European Association of Cardiovascular Imaging, < 5 % of the study population had possible preclinical left ventricular diastolic dysfunction. The present study established normal ranges for maxLAVi and minLAVi in a well-characterized population-based subset without apparent cardiovascular disease or other factors potentially associated with left atrial volume enlargement.

  • 16. Hysing, Per
    et al.
    Jonason, Tommy
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Prevalence and prognostic impact of electrocardiographic abnormalities in outpatients with extracardiac artery disease2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 5, p. 823-829Article in journal (Refereed)
    Abstract [en]

    Identifying cardiac disease in patients with extracardiac artery disease (ECAD) is essential for clinical decision-making. Electrocardiography (ECG) is an easily accessible tool to unmask subclinical cardiac disease and to risk stratify patient with or without manifest cardiovascular disease (CV). We aimed to examine the prevalence and prognostic impact of ECG changes in outpatients with ECAD. Outpatients with carotid or lower extremity artery disease (n = 435) and community-based controls (n = 397) underwent resting ECG. The patients were followed during a median of 4.8 years for CV events (hospitalization or death caused by ischaemic heart disease, cardiac arrest, heart failure, or stroke). ECG abnormalities were classified according to the Minnesota Code. Major (33% versus 15%, P<0.001) but not minor ECG abnormalities (23% versus 26%, P = 0.42) were significantly more common in patients versus controls. During the follow-up, 141 patients experienced CV events. Both major ECG abnormalities [hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.11-2.25, P = 0.012] and any ECG abnormalities (HR 1.57, 95% CI 1.06-2.33, P = 0.024) were significantly associated with CV events after adjustment for potential risk factors. In conclusion, ECG abnormalities were common in these outpatients with ECAD. Major and any ECG abnormalities were independent predictors of CV events. Addition of easily accessible ECG information might be useful in risk stratification for such patients.

  • 17.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Hedberg, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Biomarkers in addition to clinical characteristics for prediction of peripheral artery disease in patients with recent myocardial infarctionIn: Article in journal (Other academic)
    Abstract [en]

    Abstract

    Background Few studies have examined biomarkers in CAD and peripheral artery disease (PAD), their association and the ability to predict PAD.

    Methods: Two prospectively observational studies including unselected patients with recent myocardial infarction were used for the analyses. PAD was defined as an abnormal ankle brachial index (ABI) score (<0.9 or > 1.4) on at least one side. The proximity extension assay (PEA) technique was used to simultaneously analyze 92 biomarkers with association to cardiovascular disease in samples early after an acute MI. Random forest was used to identify the biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics were analyzed by the c-statistics.

    Results:  Six biomarkers were identified associated with prediction of PAD in the REBUS cohort. Three of these could be validated in the VaMIS cohort; Tumor necrosis factor receptor (TNFR-1),  Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) with an increase in c-statistics; Tnfr1:0.709 (95% CI 0.640, 0.779) and 0.746 (95% CI 0.706,0.787), Tnfr2: 0.703 (95% CI 0.633, 0.773) and 0.745 (95% CI 0.704, 0.785), GDF-15: 0.710 (95% CI 0.640, 0.781) and 0.752 (95% CI 0.711, 0.792) in the REBUS and VaMIS cohort respectively. Adding a group of biomarkers to clinical characteristics further increased the c-statistics compared to a single biomarker.

    Conclusions: Three biomarkers out of a panel of 92; TNFR-1, TNFR-2 and GDF-15 were identified associated with PAD in MI patients and could improve prediction of PAD in addition to clinical characteristics.

     

     

  • 18.
    Nilsson, Göran
    et al.
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Hedberg, P
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Jonasson, T
    Lönnnberg, I
    Öhrvik, J
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    QTc interval and survival in 75-year-old men and women from the general population.2006In: Europace, ISSN 1099-5129, Vol. 8, no 4, p. 233-40Article in journal (Refereed)
  • 19.
    Nilsson, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Jonason, Tommy
    Lönnberg, Ingemar
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Heart rate recovery is more strongly associated with the metabolic syndrome, waist circumference, and insulin sensitivity in women than in men among the elderly in the general population2007In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 154, no 3, p. 460.e1-460.e7Article in journal (Refereed)
    Abstract [en]

    Background: Low heart rate recovery (HRR) at exercise test and the metabolic syndrome (MetS) are both predictors of cardiovascular morbidity and mortality. We studied in 75-year-old women and men, representative of the general population, the relationship between (1) HRR and the MetS, (2) HRR and the individual components of the MetS, and (3) HRR and insulin sensitivity. Methods: A cross-sectional study of randomly selected 75-year-olds from a general population was performed (191 women and 194 men). The MetS was defined according to the National Cholesterol Education Program criteria. Heart rate was measured as beats per minute immediately after exercise and at 4 minutes into recovery. Results: Heart rate recovery (median and interquartile range, beat/min) was 48 (37-58) for women and 49 (38-58) for men. Thirty-seven percent of the women and 25% of the men had the MetS. Heart rate recovery was 52 (42-61) for women with the MetS and 42 (31-49) for those without. The corresponding values for men was 50 (39-61) and 47 (35-54); the difference between individuals with and without the MetS was significant for women (P < .001) but not for men (P = .084). The following significant correlation coefficients between HRR and MetS components were found: for women, waist circumference (-0.43, P < .001), high-density lipoprotein cholesterol (0.37, P < .001), insulin sensitivity (-0.37, P < .001), fasting plasma glucose (-0.30, P < .001), and triglycerides (-0.24, P = .001); for men, triglycerides (-0.20, P = .005). The sex disparity in the strength of correlation reached statistical significance for insulin sensitivity (P < .001) and waist circumference (P = .042). Conclusion: Among 75-year-olds, the MetS and related components are more strongly correlated to HRR in women than in men.

  • 20.
    Nilsson, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ohrvik, John
    Inflammation and the Metabolic Syndrome: Clustering and Impact on Survival in a Swedish Community-Based Cohort of 75 Year Olds2013In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 11, no 2, p. 92-101Article in journal (Refereed)
    Abstract [en]

    Background: High blood concentrations of inflammatory markers, including white blood cell (WBC) count, are closely related to the metabolic syndrome. Both conditions predict dismal survival. We determined prospective associations between mortality and factors derived by a factor analysis of WBC count and the basic components of the metabolic syndrome. Methods and Results: We performed a factor analysis of WBC count and the continuous components of the metabolic syndrome in 196 men and 200 women, comprising 64% of the originally invited 75 year olds from the Swedish city Vasteras. The analysis revealed three factors in men and two in women. The first factor included fasting glucose, high-density lipoprotein cholesterol, triglycerides, and waist circumference in men and in addition WBC count in women. The second factor included diastolic blood pressure and systolic blood pressure in both sexes. In men, the third factor included fasting glucose and WBC count. These factors explained 66% (first factor, 28%; second factor, 23%; third factor, 15%) of the variation in men and 57% (first factor, 34%; second factor, 23%) in women. Prospective associations of the derived factors and all-cause mortality during 10-year follow-up were assessed by Cox regression [hazard ratio (HR)]. The first factor was significantly related to increased mortality in men: HR=1.22 [95% confidence interval (CI) 1.05-1.41; p = 0.008] and women: HR=1.25 (95% CI 1.06-1.48; p = 0.010). Pooling men and women adjusting for established cardiovascular risk factors gave HR= 1.16 (95% CI 1.04-1.29; p = 0.010). In men the third factor was significantly related to mortality; HR= 1.29 (95% CI 1.07-1.57; p = 0.009). Conclusions: A metabolic inflammatory factor and a blood pressure factor were identified. In men, the former was split into a metabolic and an inflammatory factor. Factors including metabolic and inflammatory components were significantly related to 10-year mortality and the relation remained after adjusting for established cardiovascular risk factors.

  • 21.
    Nilsson, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Survival of the fattest: unexpected findings about hyperglycaemia and obesity in a population based study of 75-year-olds2011In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 1, no 1, article id e000012Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the relationship between body mass index (BMI) and mortality among 75-year-olds with and without diabetes mellitus type 2 (DM) or impaired fasting glucose (IFG).

    DESIGN: Prospective population-based cohort study with a 10-year follow-up.

    PARTICIPANTS: A random sample of 618 of the 1100 inhabitants born in 1922 and living in the city of Västerås in 1997 were invited to participate in a cardiovascular health survey; 70% of those invited agreed to participate (432 individuals: 210 men, 222 women).

    OUTCOME MEASURES: All-cause and cardiovascular mortality.

    RESULTS: 163 of 432 (38%) participants died during the 10-year follow-up period. The prevalence of DM or IFG was 41% (35% among survivors, 48% among non-survivors). The prevalence of obesity/overweight/normal weight/underweight according to WHO definitions was 12/45/42/1% (14/43/42/1% among survivors, 9/47/42/2% among non-survivors). The hazard rate for death decreased by 10% for every kg/m(2) increase in BMI in individuals with DM/IFG (HR 0.91, 95% CI 0.86 to 0.97; p=0.003). After adjustment for sex, current smoking, diagnosed hypertension, diagnosed angina pectoris, previous myocardial infarction and previous stroke/transient ischaemic attack, the corresponding decrease in mortality was 9% (HR 0.92, 95% CI 0.86 to 0.99; p=0.017). These findings remained after exclusion of individuals with BMI<20 or those who died within 2-year follow-up. In individuals without DM/IFG, BMI had no effect on mortality (HR 1.01, 95% CI 0.95 to 1.07; p=0.811). The HR for BMI differed significantly between individuals with and without DM/IFG (p interaction=0.025). The increased all-cause mortality in individuals with DM/IFG in combination with lower BMI was driven by cardiovascular death.

    CONCLUSION: High all-cause and cardiovascular mortality was associated with lower BMI in 75-year-olds with DM/IFG but not in those without DM/IFG. Further studies on the combined effect of obesity/overweight and DM/IFG are needed in order to assess the appropriateness of current guideline recommendations for weight reduction in older people with DM/IFG.

  • 22.
    Nowak, C.
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Carlsson, A. C.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Östgren, C. J.
    Linkoping Univ, Linkoping, Sweden.
    Nyström, F. H.
    Linkoping Univ, Linkoping, Sweden.
    Alam, M.
    Dalarna Univ, Falun, Sweden.
    Feldreich, T. R.
    Dalarna Univ, Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Roig, J. J. Carrero
    Karolinska Inst, Solna, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Cordeiro, A. C.
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, E.
    Stanford Univ, Sch Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Arnlöv, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden;Dalarna Univ, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S65-S65Article in journal (Other academic)
  • 23.
    Nowak, Christoph
    et al.
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Östgren, Carl Johan
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Nyström, Fredrik H.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Alam, Moudud
    Dalarna Univ, Sch Technol & Business Studies Stat, Falun, Sweden.
    Feldreich, Tobias
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Cordeiro, Antonio C.
    Dante Pazzanese Inst Cardiol, Dept Hypertens & Nephrol, Sao Paulo, Brazil.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 8, p. 1748-1757Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (< 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

  • 24.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, Vasteras, Sweden.
    Prognostic impact of subclinical or manifest extracoronary artery diseases after acute myocardial infarction2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, p. 53-59Article in journal (Refereed)
    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.

  • 25.
    Selmeryd, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Dalen, Håvard
    Nord Trondelag Hlth Trust, Levanger Hosp, Levanger, Norway.; St Olavs Univ Hosp, Dept Cardiol, Trondheim, Norway; Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, Cardiac Exercise Res Grp, Trondheim, Norway.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Clin Physiol, Västerås, Sweden.
    Derivation and Evaluation of Age-Specific Multivariate Reference Regions to Aid in Identification of Abnormal Filling Patterns: The HUNT and VaMIS Studies2018In: JACC Cardiovascular Imaging, ISSN 1936-878X, E-ISSN 1876-7591, Vol. 11, no 3, p. 400-408Article in journal (Other academic)
    Abstract [en]

    Objectives: This study aimed to derive age-specific multivariate reference regions (MVRs) able to classify subjects into those having normal or abnormal filling patterns and to evaluate the prognostic impact of this classification.

    Background: The integration of several parameters is necessary to diagnose disorders of left ventricular (LV) filling because no single measurement accurately describes the complexity of diastolic function. However, no generally accepted validated multiparametric algorithm currently exists.

    Methods: A cohort of 1,240 apparently healthy subjects from HUNT (Nord-Trøndelag Health Study) with measured early (E) and late (A) mitral inflow velocity and early mitral annular diastolic tissue velocity (e′) were used to derive univariate 95% reference bands and age-specific MVRs. Subsequently, the prognostic impact of this MVR-based classification was evaluated by Cox regression in a community-based cohort (n = 726) and in a cohort of subjects with recent acute myocardial infarction (n = 551). Both evaluation cohorts were derived from VaMIS (the Västmanland Myocardial Infarction Study).

    Results: Univariate reference bands and MVRs are presented graphically and as regression equations. After adjustment for sex, age, hypertension, body mass index, diabetes, prior ischemic heart disease, LV mass, LV ejection fraction, and left atrial size, the hazard ratio associated with abnormal filling patterns in the community-based cohort was 3.5 (95% confidence interval: 1.7 to 7.0; p < 0.001) and that in the acute myocardial infarction cohort was 1.8 (95% confidence interval: 1.1 to 2.8; p = 0.011).

    Conclusions: This study derived age-specific MVRs for identification of abnormal LV filling patterns and showed, in a community-based cohort and in a cohort of patients with recent acute myocardial infarction, that these MVRs conveyed important prognostic information. An MVR-based classification of LV filling patterns could lead to more consistent diagnostic algorithms for identification of different filling disorders.

  • 26. Selmeryd, Jonas
    et al.
    Sundstedt, Milena
    Nilsson, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Impact of left ventricular geometry on long-term survival in elderly men and women2014In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 34, no 6, p. 442-448Article in journal (Refereed)
    Abstract [en]

    Background: Adverse loading conditions and cardiac injury lead to remodelling of the heart into different patterns of left ventricular (LV) geometry. Geometry can be classified into LV hypertrophy (LVH), concentric remodelling (CR) or normal geometry (NG). The prognostic implications of the different geometric patterns have been extensively studied in middle-aged subjects, but data are scarcer for elderly populations. Methods: From a community-based random sample of 75-year-old men and women, subjects with normal LVEF were selected (n = 303). All-cause and cardiovascular mortality was analysed by LV geometry with Cox regression (unadjusted and adjusted for sex, prevalent hypertension, smoking, diabetes and prevalent ischaemic heart disease). Median follow-up time was 9.9 years. Results: Prevalence of CR and LVH was 19% and 17%, respectively. Hazard ratios (HRs) for CR were 0.93 (95% CI 0.54-1.58) for all-cause and 1.13 (0.48-2.65) for cardiovascular mortality. HRs for LVH were 2.01 (1.30-3.10) for all-cause and 3.55 (1.89-6.67) for cardiovascular mortality. As non-proportionality was present in the form of an increasing hazard for LVH, we partitioned the follow-up time at the median event time (approximately 7 years) and performed Cox regression separately within each time period. HRs for LVH during the first period were 1.23 (0.63-2.42) for all-cause and 1.79 (0.69-4.65) for cardiovascular mortality, while HRs for the second period were 3.06 (1.73-5.41) for all-cause and 6.60 (2.82-15.39) for cardiovascular mortality. Conclusion: In this community-based sample of 75-year-old men and women with normal LVEF, LVH was associated with an adverse prognosis during long-term follow-up, whereas CR was not.

  • 27.
    Skau, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 15, p. 1576-1583Article in journal (Refereed)
    Abstract [en]

    Background The Proximity Extension Assay proteomics chip provides a large-scale analysis of 92 biomarkers linked to cardiovascular disease or inflammation. We aimed to identify the biomarkers that best predicted long-term all-cause mortality in patients with acute myocardial infarction. Methods In this prospective cohort study, 92 biomarkers were analysed in 847 consecutive patients from the Vastmanland Myocardial Infarction Study with a median follow-up of 6.9 years. Results The mean ( standard deviation) age of the patients was 70 (11.8) years and 32.7% were female. Two hundred and seven patients had died after follow-up. The biomarkers most strongly linked to all-cause mortality were growth differentiation factor 15 (GDF-15) and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2). Cox regression analysis showed that GDF-15 (hazard ratio 1.25 per unit change, 95% confidence interval, 1.02-1.53, p=0.031) and TRAIL-R2 (hazard ratio 1.37 per unit change, 95% confidence interval 1.12-1.67, p=0.002) were independent predictors of long-term all-cause mortality after adjusting for age, gender, diabetes, previous myocardial infarction, stroke, heart failure, hypertension, smoking, hypercholesterolaemia, body mass index, ST-elevation myocardial infarction, left ventricular ejection fraction, troponin I, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide and C-reactive protein. The combination of GDF-15 and TRAIL-R2 with established risk factors and biomarkers showed a discriminating accuracy of separating survivors from non-survivors with a cross-validated area under the receiving operating characteristics curve of 0.88 within five years. Conclusion GDF-15 and TRAIL-R2 were the most powerful Proximity Extension Assay chip biomarkers in predicting long-term all-cause mortality in patients with acute myocardial infarction.

  • 28.
    Sundstedt, Milena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Jonason, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Brodin, Lars-Åke
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Left ventricular volumes during exercise in endurance athletes assessed by contrast echocardiography2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Aim:  The objective was to assess left ventricular (LV) volumes at rest and during upright submaximal exercise in endurance athletes to see whether changes in heart volume could explain the large predicted increase in cardiac output in endurance athletes.

    Method:  Contrast echocardiography was used to assess changes in LV volumes during upright bicycle exercise in 24 healthy male endurance athletes. Maximal oxygen uptake and oxygen pulse were measured by using cardiopulmonary exercise testing.

    Results:  From rest to exercise at a heart rate of 160 beats min−1 end-diastolic volume increased by 18% (P < 0.001) and end-systolic volume decreased by 21% (P = 0.002). Stroke volume showed an almost linear increase during exercise (45% increase, P < 0.001). The increase in end-diastolic volume contributed to 73% of the increase in stroke volume. No significant differences were observed between stroke volume calculated from LV volumes with contrast echocardiography and stroke volume calculated from oxygen pulse at heart rates of 130 and 160 beats min−1. Using the linear regression equation between oxygen uptake and cardiac output assessed by echocardiography during exercise (r = 0.87, P = 0.002), cardiac output at maximal exercise was estimated at 33 ± 3 L min−1, with an estimated increase in stroke volume by 69% from rest to maximal exercise.

    Conclusion:  By using contrast echocardiography, a large increase in stroke volume in endurance athletes could be explained by an almost linear increase in end-diastolic volume and an initial small decrease in end-systolic volume during incremental upright exercise.

  • 29.
    Sundstedt, Milena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Jonason, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Echocardiographic doppler assessments of left ventricular filling and ejection during upright exercise in endurance athletes2007In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 27, no 1, p. 36-41Article in journal (Refereed)
    Abstract [en]

    Doppler echocardiography was used to describe left ventricular filling and ejection during upright bicycle exercise in 24 healthy male endurance athletes. The transmitral pressure gradient was estimated and isovolumetric relaxation, filling and ejection time and transmitral and aortic flow velocities were measured at rest and during exercise. From rest to peak exercise (at a heart rate of 160 bpm), the mean left ventricular filling time was shortened by 73%, the ejection time by 31%, while the isovolumetric relaxation time was shortened by 62%. At peak exercise, the maximum aortic flow velocity almost doubled and the maximum transmitral flow velocity more than doubled, with a tenfold increase in the mean transmitral pressure gradient. The increase was significant (P<0·001) at each level of exercise. The left ventricular filling rate measured as volume per time was 185 ± 62 ml s−1 at rest and it increased to 986 ± 192 ml s−1 at peak exercise. This study demonstrates large changes in diastolic filling indices during upright exercise and it shows that the heart is able to increase its filling rate five times from rest to peak exercise.

  • 30.
    Velders, Matthijs A.
    et al.
    Vastmanland Cty Hosp, Dept Med, Sigtunagatan, S-72189 Vasteras, Sweden.
    Calais, Fredrik
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Dahle, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Huddinge, Sweden.
    Tenerz, Åke
    Vastmanland Cty Hosp, Dept Med, Sigtunagatan, S-72189 Vasteras, Sweden.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Clin Physiol, Vasteras, Sweden.
    Cathepsin D improves the prediction of undetected diabetes in patients with myocardial infarction2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 187-192Article in journal (Refereed)
    Abstract [en]

    Background: Newer therapeutic agents for type 2 diabetes mellitus can improve cardiovascular outcomes, but diabetes remains underdiagnosed in patients with myocardial infarction (MI). We sought to identify proteomic markers of undetected dysglycaemia (impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) to improve the identification of patients at highest risk for diabetes.

    Materials and methods: In this prospective cohort, 626 patients without known diabetes underwent oral glucose tolerance testing (OGTT) during admission for MI. Proximity extension assay was used to measure 81 biomarkers. Multivariable logistic regression, adjusting for risk factors, was used to evaluate the association of biomarkers with dysglycaemia. Subsequently, lasso regression was performed in a 2/3 training set to identify proteomic biomarkers with prognostic value for dysglycaemia, when added to risk factors, fasting plasma glucose, and glycated haemoglobin A1c. Determination of discriminatory ability was performed in a 1/3 test set.

    Results: In total, 401/626 patients (64.1%) met the criteria for dysglycaemia. Using multivariable logistic regression, cathepsin D had the strongest association with dysglycaemia. Lasso regression selected seven markers, including cathepsin D, that improved prediction of dysglycaemia (area under the receiver operator curve [AUC] 0.848 increased to 0.863). In patients with normal fasting plasma glucose, only cathepsin D was selected (AUC 0.699 increased to 0.704).

    Conclusions: Newly detected dysglycaemia, including manifest diabetes, is common in patients with acute MI. Cathepsin D improved the prediction of dysglycaemia, which may be helpful in the a priori risk determination of diabetes as a motivation for confirmatory OGTT.

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