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》

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

Yuan J ，Zhao J ，Qin Y ，Xing Y ，Yu Z ，Zhang Y ，Wu H ，Zheng Q ，Hui Y ，Guo S ，Wang A ，Han M ，Ning X ，Sun S ... -  《-》

Changes in serum uric acid and the risk of cardiovascular disease and all-cause mortality in the general population.

Longitudinal evidence on change in serum (SUA) with risk of cardiovascular disease (CVD) and all-cause mortality is limited, as many prior studies focused on baseline SUA. Further, the optimal threshold range of SUA change is unclear. A total of 63,127 participants without history of CVD were enrolled. Change in SUA was determined by the difference of SUA levels between 2006 and 2010, which divided by baseline SUA was percent change in SUA. Multivariable Cox proportional hazards models were used to calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). Our analysis also included restricted cubic spline model and three-piecewise Cox proportion hazards model to address the non-linearity between percent change in SUA and outcomes. During a median follow-up of 7.04 years, 3341 CVD and 3238 deaths occurred. We did not observed a significant association between changes in SUA and CVD. However, changes in SUA at extreme were associated with higher risk of all-cause mortality, the HRs (95% CIs) were 1.15 (1.02-1.29) and 1.20 (1.06-1.35) in the first and fifth quintile group, compared with the third quintile group. We further found a U-shaped association between percent change in SUA and all-cause mortality, and the optimal range was within 20%. Changes in SUA at extreme were risk factors for all-cause mortality, but not for CVD in the general population. The findings are relevant for role of SUA in the management of CVD risk and may contribute to improve identification of patients at higher risk.

Tian X ，Wang A ，Zuo Y ，Chen S ，Ma Y ，Han X ，Zhang L ，Wu S ，Luo Y ... -  《-》

Relationship between Serum Uric Acid and Mortality Risk in Hemodialysis Patients: A Multicenter Prospective Cohort Study.

Several studies have reported that low serum uric acid (SUA) levels are related to increased risk of mortality in maintenance hemodialysis (MHD) patients. However, the possible detrimental effects of high SUA on the mortality risk have not been well examined. Moreover, the possible effect modifiers for the SUA-mortality association have not been fully investigated. To address the aforementioned gap, we aimed to explore the nonlinear relationship between SUA levels and all-cause and cardiovascular disease (CVD) mortality risk, and to examine any possible effect modifiers in MHD patients. We conducted a multicenter, prospective cohort study among 1,018 MHD patients from 8 hemodialysis centers. The primary outcome was all-cause mortality, and the secondary outcomes were CVD mortality and non-CVD mortality. The mean value for SUA in the total population was 8.5 ± 1.9 mg/dL. The lowest and highest quintiles of SUA were <7.0 and >10.1 mg/dL, respectively. Over a median follow-up of 45.6 months, 343 deaths were recorded, of which 202 (58.9%) were due to CVD. When SUA was assessed as quintiles, a significantly higher risk of all-cause mortality was found in patients in quintile 1 (<7.0 mg/dL; hazard ratio [HR], 1.33; 95% confidence interval [CI]: 1.02-1.73) or quintile 5 (≥10.1 mg/dL; HR, 1.47; 95% CI: 1.09-2.00), compared to those in quintiles 2-4 (7-10.1 mg/dL). Moreover, the U-shaped SUA-mortality association was mainly found in those with lower C-reactive protein levels (<3 compared with ≥3 mg/L; p for interaction = 0.018). Similar trends were found for CVD mortality and non-CVD mortality. There was a U-shaped relationship between SUA levels and the risk of all-cause mortality, CVD mortality, and non-CVD mortality in MHD patients.

Yang Y ，Qin X ，Li Y ，Yang S ，Chen J ，He Y ，Huang Y ，Lin Z ，Li Y ，Kong Y ，Lu Y ，Zhao Y ，Wan Q ，Wang Q ，Huang S ，Liu Y ，Liu A ，Liu F ，Hou FF ，Liang M ... -  《-》

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 ... -  《-》