Proteinuria and risk for stroke and coronary heart disease during 27 years of follow-up: the Honolulu Heart Program.

Background: Urinary protein excretion has been linked to coronary heart disease (CHD); the relationship to stroke is less clear. We assessed whether urine dipstick screening for protein predicted stroke and CHD in the Honolulu Heart Program cohort.

Methods: Prospective, observational study of 6252 Japanese American men in Honolulu aged 45 to 68 years. Proteinuria was detected by means of urine dipstick screening during the first and third examinations. Subjects were classified as having no proteinuria if results were negative at both examinations, transient proteinuria if results were positive at 1 examination, and persistent proteinuria if results were positive at both examinations. Relative risk was derived using those subjects with no proteinuria as the reference. Outcomes were assessed through 27 years.

Results: No proteinuria was found in 92.8% of subjects, transient proteinuria in 6.1%, and persistent proteinuria in 1.1%. The age-adjusted incident stroke rates were 3.7, 7.3, and 11.8 per 1000 person-years in subjects with no, transient, or persistent proteinuria, respectively (P<.001). Age-adjusted rates of incident CHD were 9.4, 15.8, and 35.2 events per 1000 person-years, respectively (P<.001). Using Cox proportional hazards models, adjusting for age, body mass index, physical activity, smoking status, cholesterol level, presence of hypertension or diabetes mellitus, and alcohol consumption, the relative risk for 27-year incident stroke was 1.66 (95% confidence interval, 1.21-2.30; P = .002) with transient proteinuria and 2.84 (95% confidence interval, 1.51-5.34; P = .001) with persistent proteinuria, and relative risk for 27-year incident CHD was 1.48 (95% confidence interval, 1.19-1.83; P<.001) with transient proteinuria and 3.72 (95% confidence interval, 2.62-5.27; P<.001) with persistent proteinuria.

Conclusion: Proteinuria detected at urine dipstick screening independently predicted increased risk for incident stroke and incident CHD over 27 years in this cohort.