Uric Acid and Mortality in Elderly Chinese: A 10‐Year Population‐Based Cohort Study

To the Editor: Cardiovascular disease (CVD) remains one of the leading causes of mortality worldwide. Many traditional chronic diseases such as hypertension and diabetes mellitus are known CVD risk factors. Hyperuricemia is recognized as a nontraditional risk factor for CVD in some studies, but the link between hyperuricemia and mortality from CVD is unclear.1, 2 In the general adult population, serum uric acid (UA) is reportedly an independent predictor of CVD mortality,3 but this is less the case in elderly adults.4 The current study investigated the relationships between high serum UA and CVD and all-cause mortality in elderly Chinese. Of 1,774 individuals aged 65 and older recruited in 1998 from Chung-Hsing village in Taiwan, 1,093 participated in this study; 588 with completed blood test data and questionnaires were analyzed. All deaths that occurred between study entry and December 2008 were included. Deaths with International Classification of Diseases, Ninth Revision, codes 390 to 459 were classified as CVD-related deaths. Anthropometric measurements (e.g., age, height, weight, blood pressure), laboratory tests (e.g., serum albumin, total cholesterol, triglyceride, fasting glucose, creatinine, and UA), and demographic characteristics (income, education, smoking, alcohol consumption, exercise) were examined. Body mass index (BMI) was used to define weight categories according to the Taiwan Department of Health. Hypertension, type 2 diabetes mellitus, hypertriglyceridemia, and hypercholesterolemia were diagnosed according to higher-than-normal values or history of currently or previously received medical therapy. Chronic kidney disease was divided into five severity categories according to estimated glomerular filtration rate (eGFR) from the Cockcroft–Gault formula. Serum UA levels (mg/dL) were divided into quartiles (I, 1.20–5.75; II, 5.75–6.85; III, 6.85–8.15; IV, 8.15–14.10). Statistical analyses were performed using SPSS for Windows, version 17 (SPSS, Inc., Chicago, IL). Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) for CVD and all-cause mortality. The institutional review board of the China Medical University Hospital granted ethical approval for patient recruitment and data analysis. Informed consent was obtained from all participants. There were 183 deaths during the 10 years of follow-up, 55 of which were due to CVD. Using Cox proportional hazards regression analyses after adjustment for age, sex, smoking, alcohol consumption, physical activity, education level, economic status, BMI, and chronic disease (hypertension, diabetes mellitus, hypercholestemia, hypertriglyceridemia, chronic kidney disease), compared with UA quartile I RR (95% CI) for CVD mortality was 1.33 (95% confidence interval (CI) = 0.44–3.97) for quartile II, 1.12 (95% CI = 0.36–3.46) for quartile III, and 3.04 (95% CI = 1.08–8.60) for quartile IV. The RR for all-cause mortality among the UA quartiles II, III, and IV was 1.19 (95% CI = 0.68–2.08) for quartile II, 1.27 (95% CI = 0.74–2.20) for quartile III, and 1.82 (95% CI = 1.03–3.25) for quartile IV (Table 1). After excluding participants who died during the first year of follow-up, the adjusted RRs for CVD and all-cause mortality for participants in the highest UA quartile (UA IV) were 3.41 (95% CI = 1.18–9.86) and 1.82 (95% CI = 1.02–3.26), respectively, compared with participants in UA quartile I (Table 1). This population-based prospective study demonstrated that elderly Taiwanese with hyperuricemia had a greater risk of CVD or all-cause mortality. This association persisted after adjusting for the influence of CVD risk factors or excluding participants who died during the first year of follow-up. There was a positive correlation between hyperuricemia and CVD mortality and all-cause mortality, although traditional CVD factors could not fully explain the association. Several possible explanations have been proposed to explain the correlation. First, hyperuricemia was directly associated with insulin resistance,5 which may trigger the development of many metabolic abnormalities, such as diabetes mellitus and CVD.6 Second, high serum UA levels have been reported to cause endothelial damage through oxidative-redox stress.7 Third, it has been hypothesized that hyperuricemia activates the renin-angiotensin system, stimulating renovascular constriction and increasing blood pressure.8 Fourth, systemic inflammation may play a role in the relationship between hyperuricemia and CVD mortality. High C-reactive protein levels are an established risk factor for CVD mortality.9 Fifth, serum leptin levels have been found to be independently and significantly associated with CVD.10 In conclusion, the results from this 10-year prospective study demonstrate that hyperuricemia is an independent risk factor for CVD and all-cause mortality in elderly Taiwanese. Although several possible mechanisms had been proposed, further research is necessary to clarify these associations. Measurement of serum UA is easy and inexpensive, making this a convenient alternative for routine monitoring of risk, particularly in elderly adults. The authors thank all participating subjects. Conflict of Interest: This study was supported by grants from the National Science Council of Taiwan (NSC92–2314-B-039–020), the Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH101-TD-B-111–004), and from China Medical University Hospital (DMR-96–118, DMR-97–149, DMR-98–090, and DMR-99–110). Author contributions: Not stated. Sponsor's Role: Not stated.