Spontaneous platelet aggregation as a predictive risk factor for vascular occlusions in healthy volunteers? Results of the HAPARG Study. Haemostatic parameters as risk factors in healthy volunteers.

The HAPARG Study (haemostatic parameters as risk factors in healthy volunteers) was performed in a subset of volunteers taking part in the MARISK Study (Mainzer Risikoindikatoren Studie für die koronare Herzkrankheit) sponsored by the German Ministry of Research and started in 1984. A previous study (Yamanishi et al., Thromb Haemostas 1985;54:539-543) had shown that spontaneously enhanced platelet aggregation as measured with the PAT-III-test and higher fibrinogen concentrations are significant risk factors for new vascular occlusions in diabetic patients. It was the aim of the HAPARG Study to establish whether spontaneous platelet aggregation and other hemostatic variables are independent risk factors for vascular occlusions in healthy volunteers. Employees of a chemical/pharmaceutical company aged 40-65 years and personnel of the University of Mainz, aged 30-60 years were included in this prospective study. Besides anamnestic data such as on smoking, hypertension and diabetes, blood pressure, the ankle/arm Doppler-index and an ECG were recorded and serum cholesterol, HDL, LDL, triglycerides, uric acid and glucose were measured. Men (1884) and women (989) entered the study and were followed for 4-6 years. In the age group of 30-50 years, more women than men were included. During the observation period 53 vascular occlusions occurred (36 coronary and nine cerebral events and eight peripheral vascular occlusions). Only three of these endpoints occurred in women. Besides age (odds ratio = 1.7, P = 0.02) and gender as expected risk factors, the multivariate logistic stepwise regression analysis revealed smoking (odds ratio = 2.2, P = 0.008), lower HDL-levels (odds ratio = 2.2, P = 0.013), elevated diastolic blood pressure (odds ratio = 1.4. P = 0.004) followed by spontaneous platelet aggregation (odds ratio = 1.1, P = 0.037), and slightly elevated blood glucose (P = 0.0047) as significant risk factors for men. Higher fibrinogen levels missed significance in this analysis (P = 0.059). None of the other hemostatic parameters showed a significant correlation with the vascular events. To our knowledge, this has been the first prospective trial in a large population of healthy individuals in which a platelet function parameter has been studied together with other possible risk factors. Spontaneously enhanced platelet aggregation is probably an independent risk factor and, like elevated fibrinogen and other haemostatic variables, an indicator of an ongoing active atherosclerotic process.