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Hertzel C. Gerstein, MD,MSc; Johannes F. E. Mann, MD; Qilong Yi, PhD; Bernard Zinman, MD,CM; Sean F. Dinneen, MD,MSc; Byron Hoogwerf, MD; Jean Pierre Hallé, MD; James Young, MD; Andrew Rashkow, MD; Carol Joyce, MD; Shah Nawaz, MD; Salim Yusuf, MBBS,DPhil; for the HOPE Study Investigators

JAMA. 2001;286:421-426.

Context  Microalbuminuria is a risk factor for cardiovascular (CV) events. The relationship between the degree of albuminuria and CV risk is unclear.

Objectives  To 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.

Design  The Heart Outcomes Prevention Evaluation study, a cohort study conducted between 1994 and 1999 with a median 4.5 years of follow-up.

Setting  Community and academic practices in North and South America and Europe.

Participants  Individuals 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 Measures  Cardiovascular events (myocardial infarction, stroke, or CV death); all-cause death; and hospitalization for congestive heart failure.

Results  Microalbuminuria 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%).

Conclusions  Our 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.

Author Affiliations: McMaster University, Hamilton, Ontario (Drs Gerstein, Yi, and Yusuf); Klinikum Schwabing, LMU, Munich, Germany (Dr Mann); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Dr Zinman); Addenbrookes Hospital, Cambridge, England (Dr Dinneen); Cleveland Clinic Foundation, Cleveland, Ohio (Drs Hoogwerf and Young); Université de Montréal, Montréal, Québec (Dr Hallé); Griffin Hospital, Derby, Conn (Dr Rashkow); Memorial University, St John's, Newfoundland (Dr Joyce); and Sudbury Regional Hospital, Sudbury, Ontario (Dr Nawaz).

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