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

Patients with familial hypercholesterolaemia (FH) present with high plasma total- and low density lipoprotein (LDL)-cholesterol levels and develop pre mature and often severe atherosclerosis, Elevations of total- and LDL-chole sterol levels are not only related to an increased risk of atherosclerosis, but may also exert prothrombotic effects via platelet activation leading t o acute coronary events. In the present work, the platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to the p lasma PAF-acetylhydrolase (PAF-AH) activity and to their lipidaemic profile was studied in 20 heterozygous FH patients, The PAF EC50 aggregation value s in the patient group were significantly decreased (P < 0.03) compared wit h the control group (19.5 +/- 5.2 nM and 30.4 +/- 7.2 nM, respectively). Mo reover, the maximal percentage of aggregation to 100 nM PAF was significant ly increased in the patient group compared with controls (26.5 +/- 8.2% vs 15.2 +/- 3.1%, respectively, P < 0.03). Both platelet aggregation parameter s were correlated to the plasma total- and LDL-cholesterol levels, as well as to the apolipoprotein B (apo B) levels. The maximal percentage of aggreg ation to 10 mu M 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 plas ma 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 nm ol/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 fac tor contributing to the higher atherogenicity and incidence of acute corona ry events observed in patients with heterozygous FH.