Lifestyle and Metabolic Health, Low-Grade to Clinically Elevated Albuminuria, and Cardiovascular-Renal Diseases

Abstract

Background Albuminuria from low-grade to clinically elevated range confers cardiorenal risks. Objectives The authors aimed to investigate the differential roles of lifestyle/metabolic factors in the association of fine-categorized and continuously measured urinary albumin-to-creatinine ratio (UACR) levels with cardiorenal outcomes. Methods A total of 82,509 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study were included, with a median follow-up of 3.0 years. Outcomes included incident cardiovascular disease (CVD), incident CKD, their composite, along with surrogate markers. Lifestyle factors included tobacco use, alcohol use, diet, physical activity and sleep. Metabolic factors included diabetes, hypertension, abdominal obesity, and elevated low-density lipoprotein cholesterol. Cox proportional hazard models were used to calculate hazard ratios. Results Compared to the lowest UACR, participants with mildly elevated UACR (≥10 to <30 mg/g) had a 39% higher risk of composite cardiorenal outcomes (multivariable-adjusted HR: 1.39, 95% CI: 1.29-1.50), whereas those with clinically elevated UACR (≥30 mg/g) had over double the risk (HR: 2.29, 95% CI: 2.12-2.47). A nonlinear J-shaped association was observed between continuous UACR and cardiorenal outcomes (Pnonlinearity = 0.0009), with UACR ≥10 mg/g already conferring risks, a pattern also reflected by the deterioration of PREVENT score and estimated glomerular filtration rate. Optimal lifestyle and metabolic status generally attenuated CVD risk related to low-grade albuminuria, while improvement of the latter additionally decreased CVD and cardiorenal risk, even in clinically elevated albuminuria (additive Pinteraction <0.0001). Hypertension showed the largest relative contribution to cardiorenal risk, particularly in UACR <30 mg/g. Conclusions Our findings highlighted low-grade albuminuria as a key preventive window for cardiorenal outcomes requiring both aspects of modifiable risk factors, and the cardiovascular benefits of metabolic improvement in established albuminuria.