Urinary Albumin-to-Creatinine Ratio, Cardiovascular Health, and All-Cause Mortality in Hypertension: A Nationwide Cohort Analysis

While both cardiovascular health (CVH) and urinary albumin-to-creatinine ratio (UACR) are individually associated with mortality, their combined prognostic significance and potential mechanistic interplay in adults with hypertension remain unclear. This cohort study analyzed data from 9154 hypertensive adults in the National Health and Nutrition Examination Survey 2007-2018. CVH was assessed using the American Heart Association's Life's Essential 8 score, and UACR was measured from spot urine samples. Multivariable Cox proportional hazards models, restricted cubic spline analyses, joint exposure modeling, and causal mediation analysis were used to evaluate the independent, combined, and mediating effects of UACR and CVH on all-cause mortality. Both lower CVH scores and higher UACR levels were independently associated with increased mortality. A nonlinear association was observed for each. Individuals with severely elevated UACR and poor CVH had the highest mortality risk (HR = 6.61; 95% CI, 3.72-11.74), while those with normal UACR (<10 mg/g) showed no significant mortality difference across CVH strata. Notably, even mildly elevated UACR (10-29.9 mg/g), considered within the conventional "normal" range, was associated with significantly increased mortality. Mediation analysis revealed that UACR explained 4.01% (95% CI, 2.83%-6.40%; p < 0.001) of the association between CVH and mortality. This study is the first to demonstrate that UACR not only modifies but also mediates the association between CVH and mortality in individuals with hypertension. These findings underscore the prognostic value of integrating renal and cardiovascular metrics and suggest that even low-grade albuminuria has clinical relevance.