U-Shaped Association Between Serum Uric Acid Level and Risk of Mortality: A Cohort Study.

In addition to the controversy regarding the association of hyperuricemia with cardiovascular disease (CVD) mortality, few studies have examined the impact of a low uric acid level on mortality. We undertook the present study to evaluate the relationship between both low and high uric acid levels and the risk of all-cause and cause-specific mortality in a large sample of Korean adults over a full range of uric acid levels. A cohort study was performed in 375,163 South Korean men and women who underwent health check-ups from 2002 to 2012. Vital status and cause of death were ascertained from the national death records. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality outcomes were estimated using Cox proportional hazards regression analysis. During a total of 2,060,721.9 person-years of follow-up, 2,020 participants died, with 287 CVD deaths and 963 cancer deaths. Low and high uric acid levels were associated with increased all-cause, CVD, and cancer mortality. The multivariable-adjusted HRs for all-cause mortality in the lowest uric acid categories (<3.5 mg/dl for men and <2.5 mg/dl for women) compared with the sex-specific reference category were 1.58 (95% CI 1.18-2.10) and 1.80 (95% CI 1.10-2.93), respectively. Corresponding HRs in the highest uric acid categories (≥9.5 mg/dl for men and ≥8.5 mg/dl for women) were 2.39 (95% CI 1.57-3.66) and 3.77 (95% CI 1.17-12.17), respectively. In this large cohort study of men and women, both low and high uric acid levels were predictive of increased mortality, supporting a U-shaped association between serum uric acid levels and adverse health outcomes.

Cho SK ，Chang Y ，Kim I ，Ryu S ... -  《-》

U-Shaped Association of Serum Uric Acid With All-Cause and Cause-Specific Mortality in US Adults: A Cohort Study.

In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality. This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality. During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females. Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.

Hu L ，Hu G ，Xu BP ，Zhu L ，Zhou W ，Wang T ，Bao H ，Cheng X ... -  《-》

Relationship between serum uric acid and all-cause and cardiovascular mortality in patients treated with peritoneal dialysis.

Although serum uric acid level appears to be associated with mortality in individuals treated with hemodialysis, the relationship between serum uric acid level and death is uncertain in patients treated with peritoneal dialysis (PD). Cohort study. 985 patients from a single PD center in South China followed up for a median of 25.3 months. Serum uric acid level. The association of baseline sex-specific uric acid level with all-cause and cardiovascular mortality was evaluated. Models were adjusted for age, body mass index, comorbidity score, residual kidney function, total Kt/V, allopurinol and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, and laboratory test results, including hemoglobin, serum albumin, creatinine, calcium, phosphorus, triglycerides, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Mean age was 48.3±15.4 (SD) years, and 23% had diabetes. Mean uric acid level was 7.0±1.3 (range, 3.8-19.8) mg/dL. During follow-up, 144 deaths were recorded, of which 64 were due to cardiovascular events. In multivariable models, the highest sex-specific tertile of uric acid level was associated with increased risk of all-cause mortality (HR, 1.93; 95% CI, 1.27-2.93; P=0.004) and cardiovascular mortality (HR, 3.31; 95% CI, 1.70-6.41; P<0.001) compared to the lowest tertile. Adjusted Cox regression models showed that the HRs per 1-mg/dL higher uric acid level for all-cause and cardiovascular mortality were 1.33 (95% CI, 1.14-1.56; P<0.001) and 1.44 (95% CI, 1.17-1.77; P=0.001) for men and 1.03 (95% CI, 0.86-1.24; P=0.8) and 1.16 (95% CI, 0.97-1.38; P=0.1) for women, respectively. A formal test for interaction indicated that the association of uric acid level with all-cause and cardiovascular mortality differed by sex (β = -0.06 [P=0.02] and β = -0.10 [P=0.02], respectively). Single measurement of uric acid at baseline. Cause of death determined by death certificates and expert consensus. Elevated serum uric acid level is an independent risk factor for all-cause and cardiovascular mortality in men treated with PD.

Xia X ，He F ，Wu X ，Peng F ，Huang F ，Yu X ... -  《-》

Serum uric acid predicts cardiovascular mortality in male peritoneal dialysis patients with diabetes.

Serum uric acid may predict mortality in diabetic patients and dialysis patients. However, the relationship between serum uric acid and prognosis in diabetic peritoneal dialysis (PD) patients is unclear. We conducted a cohort study of 1278 incident PD patients, (mean age 47.6 years), of which 328 (25.7%) had diabetes and 289 (22.6%) had diabetic nephropathy. During a median follow-up period of 30.7 months, 231 deaths occurred, of which 126 were ascribed to cardiovascular events. Mean serum uric acid was lower for diabetic patients than non-diabetic patients (6.8 ± 1.3 vs. 7.4 ± 1.4 mg/dL, respectively; P < 0.001). Cox regression models were adjusted for glycated hemoglobin, dialysis-related factors, traditional risk factors, and treatments. After adjustments, the highest sex-specific tertile of uric acid was associated with an increased risk of cardiovascular mortality (HR, 2.26; 95% CI, 1.14-4.48) compared to the lowest tertile in diabetic patients. Adjusted HRs per 1 mg/dL higher uric acid for all-cause and cardiovascular mortality were 1.09 (95% CI, 0.91-1.32) and 1.42 (95% CI, 1.13-1.79) for diabetic men and 1.06 (95% CI, 0.83-1.35) and 1.12 (95% CI, 0.78-1.61) for diabetic women, respectively. Elevated serum uric acid predicted a higher risk of all-cause and cardiovascular mortality in non-diabetic men but not in non-diabetic women. Elevated serum uric acid is an independent predictor of cardiovascular mortality in diabetic male PD patients.

Xia X ，Zhao C ，Peng FF ，Luo QM ，Zhou Q ，Lin ZC ，Yu XQ ，Huang FX ... -  《-》

U-Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All-Cause Mortality in the Elderly: The Role of Malnourishment.

The link between elevated serum uric acid (SUA) levels and cardiovascular disease (CVD)-related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA-predicted mortality and the effect-modifying roles of malnourishment in older people. A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1-mg/dL increment of SUA. Low SUA (<4 mg/dL) strata was categorized by malnourishment status defined as Geriatric Nutritional Risk Index <98, serum albumin <38 g/L, or body mass index <22 kg/m2. Study outcomes were all-cause and CVD-related mortality. Cox models were used to estimate hazard ratios (HRs) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow-up of 5.8 years, there were 16 439 all-cause and 3877 CVD-related deaths. Compared with the reference SUA strata of 4 to <5 mg/dL, all-cause mortality was significantly higher at SUA <4 mg/dL (HR, 1.16; 95% confidence interval, 1.07-1.25) and ≥8 mg/dL (HR, 1.13; confidence interval, 1.06-1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD-related mortality was found at the SUA level <4 mg/dL (HR, 1.19; confidence interval, 1.00-1.40) and ≥7 mg/dL (HR, 1.17; confidence interval, 1.04-1.32). Remarkably, among the low SUA (<4 mg/dL) strata, only malnourished participants had greater all-cause and CVD-related mortality. This modifying effect of malnourishment remained consistent across subgroups. SUA ≥8 or <4 mg/dL independently predicts higher all-cause and CVD-related mortality in the elderly, particularly in those with malnourishment.

Tseng WC ，Chen YT ，Ou SM ，Shih CJ ，Tarng DC ，Taiwan Geriatric Kidney Disease (TGKD) Research Group ... -  《Journal of the American Heart Association》