Increased platelet reactivity to the aggregatory effect of platelet activating factor, in vitro, in patients with heterozygous familial hypercholesterolaemia

Abstract

Patients with familial hypercholesterolaemia (FH) present with high plasma total- and low density lipoprotein (LDL)-cholesterol levels and develop premature and often severe atherosclerosis. Elevations of total- and LDL cholesterol levels are not only related to an increased risk of atherosclerosis, but may also exert prothrombotic effects via platelet activation leading to acute coronary events. In the present work, the platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to the plasma PAF-acetylhydrolase (PAF-AH) activity and to their lipidemic profile was studied in 20 heterozygous FH patients. The PAF EC(50) aggregation values in the patient group were significantly decreased ( P < 0.03) compared with the control group (19.5 5.2 nM and 30.4 7.2 nM, respectively). Moreover, the maximal percentage of aggregation to 100 nM PAF was significantly increased in the patient group compared with controls (26.5 8.2% vs 15.2 3.1%, respectively, P < 0.03). Both platelet aggregation parameters were correlated to the plasma total- and LDL-cholesterol levels, as well as to the apolipoprotein B (apo B) levels. The maximal percentage of aggregation to 10 microM ADP was also significantly increased in the patient group compared with controls (51.5 10.3% vs 32.4 9.0%, respectively, P < 0.02) but was not correlated to any plasma lipid parameter. The total plasma PAF-AH activity in the heterozygous FH patients was significantly higher compared with controls (109.8 15.9 nmol/ml per min vs 68.4 18.0 nmol/ml per min, respectively, P < 0.0001), whereas the HDL-associated PAF-AH activity did not differ significantly between the two groups. Our results suggest that the increased aggregatory response of platelets to PAF despite the significantly higher plasma PAF-AH activity, could be an important factor contributing to the higher atherogenicity and incidence of acute coronary events observed in patients with heterozygous FH.