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Elevated Serum Uric Acid Increases Risk of High LDL-C and Hypertriglyceridemia
Study Questions:
Does elevated serum uric acid (SUA) predict the development of high low-density lipoprotein cholesterol (LDL-C) as well as hypertriglyceridemia (HTG)?
Methods:
A retrospective 5-year cohort study was conducted in 6,476 healthy Japanese adults who underwent health examinations in 2004 and were re-evaluated in 2009. Subjects were excluded if they had any of the following at baseline: hypertension, diabetes, dyslipidemia, chronic kidney disease, or on medication for hyperuricemia and/or gout. High LDL-C was defined as ≥140 mg/dl, low HDL-C <40 mg/dl, and HTG ≥140 mg/dl. Elevated SUA was defined as >7.0 mg/dl in men and 6 mg/dl in women. The multivariate analysis was adjusted for age, body mass index (BMI), smoking and alcohol, baseline estimated glomerular filtration rate (eGFR), baseline SUA, and SUA change in mg/dl over the 5 years.
Results:
Mean age was 45.7 ± 10.1 years; mean BMI 22-23 kg/m2 , and 2,243 were men. A high SUA at baseline predicted an elevated LDL-C, and the risk for developing an elevated LDL-C was 16% in men and 22% in women for each 1 mg/dl increase of baseline SUA. High baseline SUA was an independent risk for developing high LDL-C both in men (odds ratio [OR], 1.159) and women (OR, 1.215) per 1 mg/dl. Change in SUA levels over the 5 years was a risk factor for elevated LDL-C, with an even greater OR than at baseline (1.71 in men and 2.03 in women for 1 mg/dl SUA change). Other risk factors included a higher baseline LDL-C, higher BMI, and higher baseline eGFR (the latter two in women only). Increased SUA over 5 years were also independent risks for developing high LDL-C and HTG, but not for low HDL-C.
Conclusions:
This is the first study to report that an elevated SUA increases the risk for developing high LDL-C, as well as hypertriglyceridemia. This may shed light into the role of SUA in cardiovascular disease.
Perspective:
These findings do not document a causal role for hyperuricemia in raising serum cholesterol, but are consistent with findings that SUA may have a role in lipogenesis and in blocking fatty acid oxidation. The impact of lowering SUA with allopurinol on lipids is not clear. Elevated uric acid has been associated with atherosclerotic cardiovascular disease, the metabolic syndrome, the HTG low HDL-C lipid phenotype, waist circumference, and elevated fasting glucose. The findings are intriguing and need to be repeated in other geographic regions and ethnic groups with the same exclusion criteria and long-term follow-up.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Smoking
Keywords: Allopurinol, Atherosclerosis, Body Mass Index, Cholesterol, LDL, Fatty Acids, Glomerular Filtration Rate, Glucose, Hypertriglyceridemia, Hyperuricemia, Lipids, Metabolic Syndrome, Phenotype, Primary Prevention, Risk Factors, Smoking, Uric Acid, Waist Circumference
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