Low-Grade Albuminuria and Incidence of Cardiovascular Disease Events in Nonhypertensive and Nondiabetic Individuals: The Framingham Heart Study

Abstract

Background— Data are limited with regard to the relations of low-grade albuminuria (below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals. Methods and Results— We examined the association of urinary albumin excretion (spot urine albumin indexed to creatinine [UACR]) and the incidence of CVD events and all-cause mortality in 1568 nonhypertensive, nondiabetic Framingham Offspring Study participants (mean age, 55 years; 58% women) free of CVD. On follow-up (median, 6 years), 54 participants (20 women) developed a first CVD event, and 49 (19 women) died. After adjustment for established risk factors, increasing UACR was associated with greater risk of CVD (hazards ratio [HR] per SD increment in log UACR, 1.36; 95% CI, 1.00 to 1.87) and death (HR per SD increment in log UACR, 1.55; 95% CI, 1.10 to 2.20). Participants with UACR greater than or equal to the sex-specific median (≥3.9 μg/mg for men, ≥7.5 μg/mg for women) experienced a nearly 3-fold risk of CVD (adjusted HR, 2.92; 95% CI, 1.57 to 5.44; P <0.001) and a borderline significantly increased risk of death (adjusted HR, 1.75; 95% CI, 0.95 to 3.22; P =0.08) compared with those with UACR below the median. The increased CVD risk associated with UACR at or above the median remained robust in analyses restricted to individuals without microalbuminuria (n=1470) and in subgroups with intermediate (n=1469) and low (n=1186) pretest probabilities of CVD. Conclusions— In our community-based sample of middle-aged nonhypertensive, nondiabetic individuals, low levels of urinary albumin excretion well below the current microalbuminuria threshold predicted the development of CVD. Our observations add to the growing body of evidence that challenges the notion that UACR <30 μg/mg indicates “normal” albumin excretion.