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Uric Acid and Cardiovascular Events: A Mendelian Randomization Study
Marcus E Kleber1, Graciela Delgado2, Tanja B Grammer2
1Fifth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany; marcus.kleber@medma.uni-heidelberg.de.
Journal of the American Society of Nephrology : JASN
|March 20, 2015
Summary
High uric acid levels are causally linked to increased cardiovascular death and sudden cardiac death. This finding highlights uric acid as a significant risk factor for heart disease in Western populations.
Area of Science:
- Cardiovascular Research
- Metabolic Health
- Genetics
Background:
- Rising prevalence of hyperuricemia, hypertension, diabetes, CKD, and cardiovascular disease in Westernized populations.
- Obesity and diet are implicated in increased uric acid levels.
- Need to establish a causal link between uric acid and cardiovascular risk.
Purpose of the Study:
- To investigate if serum uric acid is an independent and causal risk factor for cardiovascular disease.
- To examine the association between genetically predicted uric acid levels and cardiometabolic phenotypes and mortality.
Main Methods:
- Mendelian randomization study using a genetic risk score (GRS) based on eight uric acid-regulating SNPs.
- Serum uric acid measured in 3315 patients from the Ludwigshafen Risk and Cardiovascular Health Study.
- Two-stage regression with GRS as instrumental variable for logistic and Cox regression analyses.
Main Results:
- The GRS was specifically associated with uric acid levels, supporting its validity.
- Elevated uric acid showed associations with prevalent coronary artery disease.
- Genetically predicted uric acid was significantly associated with increased risk of cardiovascular death and sudden cardiac death.
Conclusions:
- High serum uric acid is causally related to adverse cardiovascular outcomes.
- Sudden cardiac death is particularly associated with elevated uric acid levels.
- Findings suggest uric acid as a potential therapeutic target for cardiovascular disease prevention.
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