URINARY EXCRETIONS OF HIGH-MOLECULAR-WEIGHT BETA-THROMBOGLOBULIN AND ALBUMIN ARE INDEPENDENTLY ASSOCIATED WITH CORONARY HEART-DISEASE IN WOMEN, A NESTED CASE-CONTROL STUDY OF MIDDLE-AGED WOMEN IN THE DIAGNOSTISCH-ONDERZOEK-MAMMACARCINOOM (DOM) COHORT, UTRECHT, NETHERLANDS

Increased plasma levels of beta-thromboglobulin, a platelet activation marker, are observed in coronary artery disease. Urinary albumin excretion, a marker of endothelial cell perturbation,_ is related to cardiovascular disease in diabetes. To test the value of these markers in predicting forthcoming coronary disease, the relations between urinary excretions of high molecular weight beta-thromboglobulin (HMW-beta TG) and albumin and subsequent coronary disease in a cohort of 15,484 middle-aged women were investigated in a nested case-control study. Baseline questionnaire data and urine samples were available from a breast cancer screening program in Utrecht during 1982-1985. Cases were Utrecht hospital admissions for myocardial infarction (n = 50) or angiographically confirmed coronary disease (n = 28) from 1982-1985 to 1990-1991. Classifying events occurred a median of 5.1 years after baseline. Controls were a random sample from the cohort, individually case matched for baseline examination date and age, at 1:2 ratio. HMW-beta TG/creatinine ratios (ng/mmol, mean +/- standard error) were 5.3 +/- 0.3 in cases and 4.7 +/- 0.3 in controls; albumin/creatinine ratios (mg/mmol, median) were, respectively, 0.37 and 0.22. Crude odds ratios for classification in the highest compared with the lowest tertiles of HMW-beta TG/creatinine and albumin/creatinine distributions were elevated for cases compared with controls: HMW-beta TG/creatinine odds ratio = 2.4, 95% confidence interval 1.1-5.0; albumin/creatinine odds ratio = 2.1, 95% confidence interval 1.0-4.1. These relations persisted after adjustment for smoking, hypertension, Quetelet index, and menopausal status. Both urinary HMW-beta TG and albumin excretion are markers of coronary disease risk in middle-aged women, indicating that increased platelet activation and endothelial cell perturbation precede coronary heart disease events in women.