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

Abstract

Background: 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.

Methods and results: 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.

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

Keywords: elderly; malnourishment; mortality; uric acid.

Figure 1

U‐shaped association between serum uric acid level with (A) all‐cause and (B) cardiovascular disease (CVD) mortality among 127 771 older people. Hazard ratios (HRs) (95% confidence intervals) of serum uric acid categories associated with (A) all‐cause and (B) CVD mortality in Cox models are depicted. Model 1 was an unadjusted crude HR. Model 2 was adjusted for age and sex. Model 3 was adjusted for age, sex, smoking, alcohol consumption, body mass index, systolic blood pressure, and baseline comorbidities (hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, and cerebrovascular disease). Model 4 included covariates from model 3, as well as laboratory biochemical profiles. Serum uric acid category of 4 to <5 mg/dL served as reference.

Figure 2

Cubic spline models for the association between serum uric acid (SUA) levels with (A through C) all‐cause and (D through F) cardiovascular disease (CVD) mortality among 127 771 older people, stratified by malnourishment status. Hazard ratios (HRs) were adjusted for age, sex, body mass index, smoking, alcohol consumption, blood pressure, estimated glomerular filtration rate, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, cerebrovascular disease, serum total cholesterol, triglycerides, high‐density lipoprotein cholesterol, hemoglobin, fasting glucose, white blood cell count, and albumin. Filled circles denote statistical significance (P<0.05) compared with the reference (diamond) SUA level of 4.5 mg/dL. Solid line (—) denotes adjusted HR and dash line (‐ ‐ ‐) denotes 95% confidence intervals (CIs).

Figure 3

Risks of (A) all‐cause and (B) cardiovascular disease (CVD) mortality by malnourishment status among participants with low serum uric acid (<4 mg/dL). Participants with a serum uric acid level of 4 to <5 mg/dL served as the reference group.

Figure 4

Subgroup analyses for effect modification by malnourishment status on (A) all‐cause and (B) cardiovascular disease (CVD) mortality risks in participants with low serum uric acid (SUA, <4 mg/dL) as compared to those with SUA of 4 to <5 mg/dL. The risks were presented as hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for all variables in Table 1. eGFR indicates estimated glomerular filtration rate.