LIPOPROTEIN-LIPASE ACTIVITY IN PATIENTS WITH COMBINED HYPERLIPEMIA

The aetiology of familial combined hyperlipidaemia remains obscure, wi th both genetic and environmental factors contributing to the phenotyp e, which is frequently associated with premature coronary heart diseas e. We have studied lipoprotein lipase (LPL) activity and hepatic lipas e (HL) activity in patients with coronary heart disease to determine w hether variation in lipase activities contributes to this phenotype. F orty-one patients (mean age 50 years; 30 male) were selected on the ba sis of cholesterol levels above 6.5 mmol/l and triglyceride levels abo ve 2.2 mmol/l, with apoprotein B values over the 90th percentile. Ther e was a family history of premature coronary heart disease in 78% and a personal history in 64%, at mean age 44, the patient group therefore predominantly corresponded to the common definition of familial combi ned hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not o ver represented. Blood samples were taken following intravenous admini stration of heparin (100 IU/kg body wt), and LPL and HL activities wer e measured. Mean post-heparin LPL was significantly lower in patients than controls 10 min after heparin administration (2.98 +/- 1.04 and 3 .86 +/- 0.93 mu mol ml(-1) h(-1), respectively, P = 0.001), and 37% pa tients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their res pective controls at 5, 10, 20 and 30 minutes postheparin. As expected, both female patients and controls had lower HL activities than males, although this sex difference did not reach statistical significance i n the patient group. Mean lipid and lipoprotein results were: choleste rol 8.2 mmol/l; triglycerides 4.2 mmol/l; high-density lipoprotein cho lesterol 0.90 mmol/l; apoprotein Al 122 mg/dl; apoprotein B 171 mg/dl; lipoprotein (a) 23 mg/dl (median 10 mg/dl). High-density lipoprotein cholesterol and triglycerides were negatively correlated (r = -0.26, P = 0.05). HL was significantly related to body mass index at all time points whereas the negative correlation between post-heparin LPL and b ody mass index was significant only 30 min after heparin administratio n. Post-heparin LPL was only weakly correlated with triglycerides 10 a nd 20 min after heparin administration. These lipid and lipoprotein re sults are clearly potentially atherogenic as indicated by the extent o f premature coronary heart disease in the group described. A decrease in LPL activity may contribute to this pattern.