Uric Acid and Cardiovascular Events: A Mendelian Randomization Study

Kleber, Marcus E; Delgado, Graciela; Grammer, Tanja B; Silbernagel, Günther; Huang, Jie; Krämer, Bernhard K; Ritz, Eberhard; März, Winfried (2015). Uric Acid and Cardiovascular Events: A Mendelian Randomization Study. Journal of the American Society of Nephrology, 26(11), pp. 2831-2838. Lippincott Williams & Wilkins 10.1681/ASN.2014070660

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Obesity and diets rich in uric acid-raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid-regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology

UniBE Contributor:

Silbernagel, Günther


600 Technology > 610 Medicine & health




Lippincott Williams & Wilkins




Catherine Gut

Date Deposited:

14 Apr 2016 10:12

Last Modified:

14 Apr 2016 10:12

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

cardiovascular disease; cardiovascular events; development; genetics; mortality risk



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