Albuminuria and Risk of Cardiovascular Events, Death, and Heart Failure in Diabetic and Nondiabetic Individuals

TLDR

Microalbuminuria is a known risk factor for cardiovascular events, but the relationship between the degree of albuminuria and cardiovascular risk remains unclear. The study aims to estimate cardiovascular event risk in high‑risk diabetic and non‑diabetic individuals with microalbuminuria and to assess whether albuminuria levels below the microalbuminuria threshold elevate cardiovascular risk. The Heart Outcomes Prevention Evaluation cohort followed 9,043 adults aged ≥55 with cardiovascular disease or diabetes and at least one cardiovascular risk factor, measuring baseline urine albumin/creatinine ratio and tracking cardiovascular outcomes over a median 4.5‑year follow‑up across community and academic practices in North and South America and Europe. Microalbuminuria was associated with a 1.8‑fold higher risk of major cardiovascular events, a 2.1‑fold higher risk of all‑cause death, and a 3.2‑fold higher risk of heart‑failure hospitalization, with risk escalating across higher albuminuria quartiles and rising 5.9% per 0.4‑mg/mmol ACR increase, indicating that any albuminuria level—even below the microalbuminuria threshold—predicts cardiovascular risk.

Abstract

ContextMicroalbuminuria is a risk factor for cardiovascular (CV) events. The relationship between the degree of albuminuria and CV risk is unclear.ObjectivesTo estimate the risk of CV events in high-risk individuals with diabetes mellitus (DM) and without DM who have microalbuminuria and to determine whether levels of albuminuria below the microalbuminuria threshold increase CV risk.DesignThe Heart Outcomes Prevention Evaluation study, a cohort study conducted between 1994 and 1999 with a median 4.5 years of follow-up.SettingCommunity and academic practices in North and South America and Europe.ParticipantsIndividuals aged 55 years or more with a history of CV disease (n = 5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine albumin/creatinine ratio (ACR) measurement.Main Outcome MeasuresCardiovascular events (myocardial infarction, stroke, or CV death); all-cause death; and hospitalization for congestive heart failure.ResultsMicroalbuminuria was detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those without DM).Compared with the lowest quartile of ACR (<0.22 mg/mmol), the RRs of the primary aggregate end point in the second quartile (ie, ACR range, 0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95% CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95% CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend <.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol increase in ACR level, the adjusted hazard of major CV events increased by 5.9% (95% CI, 4.9%-7.0%).ConclusionsOur results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria identifies people at high risk for CV events.