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Ärnlöv, Johan
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Publications (10 of 185) Show all publications
Fellström, B., Helmersson-Karlqvist, J., Lind, L., Soveri, I., Wu, P.-H., Thulin, M., . . . Larsson, A. (2020). Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females. Journal of Interferon and Cytokine Research, 40(2), 71-74
Open this publication in new window or tab >>Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
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2020 (English)In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 40, no 2, p. 71-74Article in journal (Refereed) Published
Abstract [en]

There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1 alpha, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

Keywords
HDL cholesterol, apolipoprotein A1, cytokines, multiplex assays, urine
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-394993 (URN)10.1089/jir.2019.0074 (DOI)000510520300001 ()31599692 (PubMedID)
Available from: 2019-10-11 Created: 2019-10-11 Last updated: 2020-03-20Bibliographically approved
Chang, A. R., Grams, M. E., Ballew, S. H., Bilo, H., Correa, A., Evans, M., . . . Woodward, M. (2019). Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium. BMJ. British Medical Journal, 364, Article ID k5301.
Open this publication in new window or tab >>Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium
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2019 (English)In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 364, article id k5301Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.

DESIGN: Individual participant data meta-analysis.

SETTING: Cohorts from 40 countries with data collected between 1970 and 2017.

PARTICIPANTS: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).

MAIN OUTCOME MEASURES: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality.

RESULTS: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.

CONCLUSIONS: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-373654 (URN)10.1136/bmj.k5301 (DOI)000455770800012 ()30630856 (PubMedID)
Note

Anders Larsson, Lars Lannfelt and Johan Ärnlöv are collaborators in the CKD Prognosis Consortium (CKD-PC).

Available from: 2019-01-17 Created: 2019-01-17 Last updated: 2019-04-02Bibliographically approved
Beijer, K., Nowak, C., Sundström, J., Ärnlöv, J., Fall, T. & Lind, L. (2019). In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study. Diabetologia, 62(11), 1998-2006
Open this publication in new window or tab >>In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study
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2019 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 11, p. 1998-2006Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis: The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome 'diabetes' and whether these associations were causal.

Methods: In 2467 individuals of the population-based, cross-sectional EpiHealth study (45-75 years, 50% women), 249 plasma proteins were analysed by the proximity extension assay technique. DNA was genotyped using the Illumina HumanCoreExome-12 v1.0 BeadChip. Diabetes was defined as taking glucose-lowering treatment or having a fasting plasma glucose of >= 7.0 mmol/l. The associations between proteins and diabetes were assessed using logistic regression. To investigate causal relationships between proteins and diabetes, a bidirectional two-sample Mendelian randomisation was performed based on large, genome-wide association studies belonging to the DIAGRAM and MAGIC consortia, and a genome-wide association study in the EpiHealth study.

Results: Twenty-six proteins were positively associated with diabetes, including cathepsin D, retinal dehydrogenase 1, alpha-l-iduronidase, hydroxyacid oxidase 1 and galectin-4 (top five findings). Three proteins, lipoprotein lipase, IGF-binding protein 2 and paraoxonase 3 (PON-3), were inversely associated with diabetes. Fourteen of the proteins are novel discoveries. The Mendelian randomisation study did not disclose any significant causal effects between the proteins and diabetes in either direction that were consistent with the relationships found between the protein levels and diabetes.

Conclusions/interpretation: The 29 proteins associated with diabetes are involved in several physiological pathways, but given the power of the study no causal link was identified for those proteins tested in Mendelian randomisation. Therefore, the identified proteins are likely to be biomarkers for type 2 diabetes, rather than representing causal pathways.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Diabetes, Genotyping, Mendelian randomisation, Proteomics, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-396951 (URN)10.1007/s00125-019-4960-8 (DOI)000491944900005 ()31446444 (PubMedID)
Funder
Swedish Research Council, 2015-03477Swedish Heart Lung Foundation, 20150429Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 1637
Available from: 2019-11-15 Created: 2019-11-15 Last updated: 2019-11-15Bibliographically approved
Griswold, M., Fullman, N., Hawley, C., Arian, N., Zimsen, S., Tymeson, H., . . . Gakidou, E. (2018). Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet, 392(10152), 1015-1035
Open this publication in new window or tab >>Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
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2018 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, no 10152, p. 1015-1035Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.

METHODS: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.

FINDINGS: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5-3·0) of age-standardised female deaths and 6·8% (5·8-8·0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2-4·3) of female deaths and 12·2% (10·8-13·6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2·3% (95% UI 2·0-2·6) and male attributable DALYs were 8·9% (7·8-9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0-1·7] of total deaths), road injuries (1·2% [0·7-1·9]), and self-harm (1·1% [0·6-1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2-33·3) of total alcohol-attributable female deaths and 18·9% (15·3-22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0-0·8) standard drinks per week.

INTERPRETATION: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.

FUNDING: Bill & Melinda Gates Foundation.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-363656 (URN)10.1016/S0140-6736(18)31310-2 (DOI)000445098800025 ()30146330 (PubMedID)
Available from: 2018-11-02 Created: 2018-11-02 Last updated: 2018-12-12Bibliographically approved
Wuopio, J., Hilden, J., Bring, C., Kastrup, J., Sajadieh, A., Jensen, G. B., . . . Ärnlöv, J. (2018). Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study.. Atherosclerosis, 278, 97-102
Open this publication in new window or tab >>Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study.
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2018 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 278, p. 97-102Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease.

METHODS: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs.

RESULTS: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05-1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07-1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events.

CONCLUSIONS: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.

Keywords
Cardiovascular biomarker, Cardiovascular risk, Cathepsin, Coronary heart disease, Ischemic heart disease, Mortality
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363384 (URN)10.1016/j.atherosclerosis.2018.09.006 (DOI)000451056500013 ()30261474 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationThuréus stiftelse för främjande av geriatrisk forskningMarianne and Marcus Wallenberg Foundation
Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2019-01-24Bibliographically approved
Ruge, T., Carlsson, A. C., Ingelsson, E., Risérus, U., Sundström, J., Larsson, A., . . . Ärnlöv, J. (2018). Circulating endostatin and the incidence of heart failure.. Scandinavian Cardiovascular Journal, 52(5), 244-249
Open this publication in new window or tab >>Circulating endostatin and the incidence of heart failure.
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2018 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 5, p. 244-249Article in journal (Refereed) Published
Abstract [en]

Objective: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

Design: We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

Results: Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts.

Conclusion: Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

Keywords
Heart failure, angiogenesis, anti-angiogenesis, epidemiology, left ventricular systolic function, population based studies, remodelling of extracellular matrix
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363655 (URN)10.1080/14017431.2018.1483080 (DOI)000460703000003 ()29893146 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationEU, Horizon 2020, 634869Marianne and Marcus Wallenberg Foundation, 634869Thuréus stiftelse för främjande av geriatrisk forskning
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2019-04-01Bibliographically approved
Corsonello, A., Tap, L., Roller-Wirnsberger, R., Wirnsberger, G., Zoccali, C., Kostka, T., . . . Lattanzio, F. (2018). Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study. BMC Nephrology, 19, Article ID 260.
Open this publication in new window or tab >>Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study
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2018 (English)In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 19, article id 260Article in journal (Refereed) Published
Abstract [en]

Background: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. Methods/design: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months-follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. Discussion: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Chronic kidney disease, Older people, Disability, Frailty, Ageing
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-369107 (URN)10.1186/s12882-018-1030-2 (DOI)000447187600005 ()30309342 (PubMedID)
Funder
EU, Horizon 2020, 634869
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Corsonello, A., Roller-Wirnsberger, R., Di Rosa, M., Fabbietti, P., Wirnsberger, G., Kostka, T., . . . Lattanzio, F. (2018). Estimated glomerular filtration rate and functional status among older people: A systematic review. European journal of internal medicine, 56, 39-48
Open this publication in new window or tab >>Estimated glomerular filtration rate and functional status among older people: A systematic review
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2018 (English)In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 56, p. 39-48Article, review/survey (Refereed) Published
Abstract [en]

Background: The association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes. Methods: We searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed. Results: We included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations. Conclusion: Available data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Estimated glomerular filtration rate (eGFR), Creatinine, Cystatin C, Frailty, Disability
National Category
Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-368372 (URN)10.1016/j.ejim.2018.05.030 (DOI)000446216600007 ()29936073 (PubMedID)
Funder
EU, Horizon 2020, 634869
Available from: 2018-12-05 Created: 2018-12-05 Last updated: 2018-12-05Bibliographically approved
Lind, L., Sundström, J., Ärnlöv, J. & Lampa, E. (2018). Impact of Aging on the Strength of Cardiovascular Risk Factors: A Longitudinal Study Over 40 Years. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(1), Article ID e007061.
Open this publication in new window or tab >>Impact of Aging on the Strength of Cardiovascular Risk Factors: A Longitudinal Study Over 40 Years
2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007061Article in journal (Refereed) Published
Abstract [en]

Background-The knowledge of the impact of cardiovascular risk factors at different ages has mainly been based on different studies performed at different ages. This study aimed to investigate the change in impact of traditional cardiovascular risk factors over the aging process in subjects followed for 4 decades. Methods and Results-In the ULSAM (Uppsala Longitudinal Study of Adult Men) study, 2322 men originally investigated in 1970 to 1974 have been followed regarding cardiovascular diseases until the end of 2013. This cohort has been investigated physically at ages 50, 60, 70, 77, and 82 years regarding body mass index, low-density lipoprotein-and high-density lipoprotein-cholesterol, triglycerides, systolic blood pressure and diastolic blood pressure, fasting glucose, and smoking. These data were used to model the interactions between risk factors and age regarding incident myocardial infarction (n=540), ischemic stroke (n=343), or heart failure (n=397). Significant interactions were observed between age and the set of traditional risk factors regarding all 3 outcomes (P<0.05 for all). Generally, a decline in the rate ratios was seen with aging for most risk factors, being most pronounced for body mass index regarding myocardial infarction and for systolic blood pressure regarding ischemic stroke and heart failure. However, low-density lipoprotein-cholesterol was significantly related to incident myocardial infarction, whereas both body mass index and fasting glucose were significantly related to incident heart failure also at a high age. Conclusions-Using a longitudinal design in middle-aged men spanning 4 decades showed that the impact of traditional cardiovascular risk factors generally declined with aging. However, some of the risk factors remained significantly associated with incident cardiovascular disease also at old age.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
blood pressure, cardiovascular disease, lipids and cholesterol, obesity, risk factor
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-351062 (URN)10.1161/JAHA.117.007061 (DOI)000428139900011 ()
Funder
Swedish Research Council
Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2018-05-30Bibliographically approved
Inker, L. A., Grams, M. E., Levey, A. S., Coresh, J., Cirillo, M., Collins, J. F., . . . Levin, A. (2018). Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. American Journal of Kidney Diseases, 73(2), 206-217, Article ID S0272-6386(18)30916-8.
Open this publication in new window or tab >>Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium
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2018 (English)In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 73, no 2, p. 206-217, article id S0272-6386(18)30916-8Article in journal (Refereed) Epub ahead of print
Abstract [en]

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.

STUDY DESIGN: Cross-sectional individual participant-level analyses in a global consortium.

SETTING & STUDY POPULATIONS: 17 CKD and 38 general population and high-risk cohorts.

SELECTION CRITERIA FOR STUDIES: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.

DATA EXTRACTION: Data were obtained and analyzed between July 2015 and January 2018.

ANALYTICAL APPROACH: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.

RESULTS: The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).

LIMITATIONS: Variations in study era, health care delivery system, typical diet, and laboratory assays.

CONCLUSIONS: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

Keywords
CKD Prognosis Consortium, CKD stage, Chronic kidney disease (CKD), albuminuria, anemia, diabetes, glomerular filtration rate (GFR), hematocrit, hemoglobin, hyperparathyroidism, hypertension, individual-level meta-analysis, kidney function, laboratory abnormality, laboratory tests, meta-analysis, serum bicarbonate, serum calcium, serum intact parathyroid hormone, serum phosphorus, serum potassium, staging system
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-364781 (URN)10.1053/j.ajkd.2018.08.013 (DOI)30348535 (PubMedID)
Available from: 2018-11-02 Created: 2018-11-02 Last updated: 2019-02-13Bibliographically approved
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