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

Abstract

BackgroundThe 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.Methods and ResultsA 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.Conclusions SUA ≥8 or <4 mg/dL independently predicts higher all‐cause and CVD‐related mortality in the elderly, particularly in those with malnourishment.

Repeated measurements of serum urate and mortality: a prospective cohort study of 152,358 individuals over 8 years of follow-up

“…We adjusted for these factors in our multivariable model and observed a consistent pattern of a U-shaped relationship between cumulative average serum urate and all-cause mortality, CVD mortality, and other mortalities. This relationship is consistent with previous findings from studies of Asian general population cohorts [44,45]. Results from our current study further showed that the association remained significant and independent of kidney function [21,49].…”

“…Some suggested a J-or U-shaped relationship [9][10][11][12][13][14][15] or a strong positive relationship, while others suggested a null association [16][17][18][19][20][21][22][23] or inverse association [24]. Direct evidence for healthy individuals is limited [44,45]. Further, serum urate varies over time; thus, prior studies evaluating serum urate were limited with only one single measurement of serum urate and were unable to examine the longitudinal association between long-term serum urate and mortality [31].…”

The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment

“…There is evidence that sUA causes endothelial dysfunction and is, therefore, associated with renal and cardiovascular disease and mortality [1,4], although others have not found such independent associations [5,6]. UA can increase radical formation and inhibit the degradation of adenosine diphosphate, producing more stable platelet aggregates and an increased incidence of thrombosis in arterial disease, especially in the patients with hypertension and diabetes [7][8][9][10][11]. Similarly, serum homocysteine (sHcy) is also involved in the disruption of vascular integrity and is well recognized as an independent risk factor for osteoporosis-associated fractures and cardiovascular and cerebrovascular diseases [12][13][14][15].…”

Fructose Increases Uric Acid Contributing to Metabolic Syndrome - Herbal, Nutritional and Dietary Strategies to Reduce Uric Acid

“…It has been reported that, both low (<3.5 mg/dl for men and <2.5 mg/dl for women) and high (≥9.5 mg/dl for men and ≥8.5 mg/dl for women) SUA levels are associated with increased all-cause, cardiovascular disease, and cancer mortality [79]. Yet, another study, of the elderly, reported that while low levels of SUA (< 4.0 mg/dl) were associated with degenerative neural conditions, this occurred only in the undernourished [80]. Smokers with a lower SUA were reported to suffer more respiratory disease than average SUA smokers.…”