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The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.ORCID iD: 0000-0003-2247-8454
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2011 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 9, 2820-2827 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73m(2) significantly improved IDI (0.047, P < 0.001).

CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

Place, publisher, year, edition, pages
2011. Vol. 26, no 9, 2820-2827 p.
Keyword [en]
cardiovascular diseases, epidemiology, kidney, prognosis, risk factors
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149740DOI: 10.1093/ndt/gfq848ISI: 000295231600017PubMedID: 21335440OAI: oai:DiVA.org:uu-149740DiVA: diva2:405334
Available from: 2011-03-22 Created: 2011-03-22 Last updated: 2017-12-11Bibliographically approved
In thesis
1. The Kidney in Different Stages of the Cardiovascular Continuum
Open this publication in new window or tab >>The Kidney in Different Stages of the Cardiovascular Continuum
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.

The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.

This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.

In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.

Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 946
Keyword
epidemiology, chronic kidney disease, cystatin C, glomerular filtration rate, albuminuria, euglycemic hyperinsulinemic clamp, insulin sensitivity, inflammation, oxidative stress, endothelial dysfunction and left ventricular dysfunction
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology Gerontology, specializing in Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-209644 (URN)978-91-554-8792-8 (ISBN)
Public defence
2013-12-05, Universitetshuset, sal IX, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-11-14 Created: 2013-10-22 Last updated: 2014-01-23

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Sundström, JohanLarsson, Anders

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