Urinary Excretions of High Molecular Weight β-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 β-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 β-thromboglobulin (HMW-βTG) 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 a 1 :2 ratio. HMW-βTG/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-βTG/creatinine and albumin/creatinine distributions were elevated for cases compared with controls : HMW-βTG/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-βTG 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.