Lipoprotein lipase activity in patients with combined hyperlipidaemia


The aetiology of familial combined hyperlipidaemia remains obscure, with both genetic and environmental factors contributing to the phenotype, which is frequently associated with premature coronary heart disease. We have studied lipoprotein lipase (LPL) activity and hepatic lipase (HL) activity in patients with coronary heart disease to determine whether variation in lipase activities contributes to this phenotype. Forty-one patients (mean age 50 years; 30 male) were selected on the basis of cholesterol levels above 6.5 mmol/l and triglyceride levels above 2.2 mmol/1, with apoprotein B values over the 90th percentile. There 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 combined hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not over represented. Blood samples were taken following intravenous administration of heparin (100IU/kg body wt), and LPL and HL activities were 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 μmol ml-1 h-1, respectively, P = 0.001), and 37% patients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their respective 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 in the patient group. Mean lipid and lipoprotein results were: cholesterol 8.2 mmol/1; triglycerides 4.2 mmol/l; high-density lipoprotein cholesterol 0.90 mmol/1; 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 body mass index was significant only 30 min after heparin administration. Post-heparin LPL was only weakly correlated with triglycerides 10 and 20 min after heparin administration. These lipid and lipoprotein results are clearly potentially atherogenic as indicated by the extent of premature coronary heart disease in the group described. A decrease in LPL activity may contribute to this pattern.

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familial combined hyperlipidaemia


coronary heart disease


lipoprotein lipase


hepatic lipase


high-density lipoprotein


very low density lipoprotein;






body mass index


  1. 1.

    Babirak SP, Iverius P-H, Fujimoto WY, Brunzell JD (1989) Detection and characterization of the heterozygote state for lipoprotein lipase deficiency. Arteriosclerosis 9:326–334

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Babirak SP, Brown BG, Brunzell JD (1992) Familial combined hyperlipidemia and abnormal lipoprotein lipase. Arterioscler Thromb 12:1176–1183

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Baginsky ML, Brown WV (1979) A new method for the measurement of lipoprotein lipase in postheparin plasma using sodium dodecyl sulfate for the inactivation of hepatic triglyceride lipase. J Lipid Res 20:548–556

    CAS  PubMed  Google Scholar 

  4. 4.

    Barbir M, Wile D, Trayner I, Aber VR, Thompson GR (1988) High prevalence of hypertriglyceridaemia and apolipoprotein abnormalities in coronary artery disease. Br Heart J 60:397–403

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Belfrage P, Vaughan M (1969) Simple liquid-liquid partition system for isolation of labelled oleic acid from mixtures with glycerides. J Lipid Res 10:341–344

    CAS  PubMed  Google Scholar 

  6. 6.

    Brunzell JD, Schrott HG, Motulsky AG, Bierman EL (1976) Myocardial infarction in the familial forms of hypertriglyceridemia. Metabolism 25:313–320

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Brunzell JD, Albers JJ, Chait A, Grundy SM, Groszek E, McDonald GB (1983) Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia. J Lipid Res 24:147–155

    CAS  PubMed  Google Scholar 

  8. 8.

    Chair A, Albers JJ, Brunzell JD (1980) Very low density lipoprotein overproduction in genetic forms of hypertriglyceridemia. Eur J Clin Invest 10:17–22

    Article  Google Scholar 

  9. 9.

    Durrington PN, Hunt I, Ishola M, Kane J, Stephens WP (1986) Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction. Br Heart J 56:206–212

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Goldstein JL, Hazzard WR, Schrott HG, BiermanGL, Motulsky AG (1973) Hyperlipidemia in coronary heart disease II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder combined hyperlipidaemia. J Clin Invest 52:1544–1568

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Goldstein JL, Hazzard WR, Schrott HG, Bierman EL, Motulsky AG (1973) Hyperlipidemia in coronary heart disease I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest 52:1533–1543

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Grundy, SM (1988) HMG-CoA reductase inhibitors for treatment of hypercholesterolaemia. New Eng J Med 319:24–33

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Hayden MR, Kirk H, Clark C, Frohlich J, Rabkin S, Mc Leod R, Hewitt J (1987) DNA polymorphisms in and around the apo-AI-CIII genes and genetic hyperlipidemias. Am J Hum Genet 40:421–430

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548

    CAS  PubMed  Google Scholar 

  15. 15.

    Hopkins GJ, Barter PJ (1986) Role of triglyceride-rich lipoproteins and hepatic lipase in determining the particle size and compositions of high density lipoproteins. J Lipid Res 27:1265–1277

    CAS  PubMed  Google Scholar 

  16. 16.

    Houlston RS, Lewis B, Humphries SE (1991) Polymorphisms of the apolipoproteins B and E genes and their possible roles in familial and non familial combined hyperlipidaemia. Dis Markers 9:319–325

    CAS  PubMed  Google Scholar 

  17. 17.

    Huttunen JK, Enholm C, Kekki M, Nikkila EA (1976) Postheparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridaemia: correlations to sex, age and various parameters of triglyceride metabolism. Clin Sci Molec Med 50:249–260

    CAS  Google Scholar 

  18. 18.

    Karpe F, Tornvall P, Olivecrona T, Steiner G, Carlson LA, Hamsten A (1993) Composition of human low density lipoprotein: effects of post-prandial triglyceride-rich lipoproteins, ipoprotein lipase, hepatic lipase and cholesteryl ester transfer protein. Atherosclerosis 98:33–49

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Labeur C, Rosseneu M, Henderson LO (1992) Results of two international surveys on Lp(a) measurements (abstract). 2nd International Conference on Lp(a), New Orleans, p 83

  20. 20.

    Lipid Research Clinics Coronary Primary Prevention Trial Results (1984) Reduction in incidence of coronary heart disease. JAMA 251:351–374

    Article  Google Scholar 

  21. 21.

    Mailly F, Moll P, Kottke BA, Kamboh MI, Humphries SE, Ferrell RE (1992) Estimation of the frequency of isoformgenotype discrepancies at the apolipoprotein E locus in heterozygotes for the isoforms. Genet Epidemial 9:239–248

    CAS  Article  Google Scholar 

  22. 22.

    McNamara JR, Campos H, Ordovas JM, Peterson J, Wilson PW, Schaefer EJ (1987) Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study. Arteriosclerosis 7:483–490

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Miller GJ, Miller NE (1975) Plasma high density lipoprotein concentration and the development of ischaemic heart disease. Lancet I: 16–19

    Article  Google Scholar 

  24. 24.

    Miller GJ, Cruickshank JK, Ellis LJ, Thompson RL, Wilkes HC, Stirling Y, Mitropoulos KA, Allison JV, Fox TE, Walker AO (1989) Fat consumption and factor VII coagulant activity in middle aged men. An association between a dietary and thrombogenic coronary risk factor. Atherosclerosis 78:19–24

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Nikila EA, Aro A (1973) Family study of lipids and lipoproteins in coronary heart-disease. Lancet I: 954–958

    Article  Google Scholar 

  27. 27.

    Nilsson-Ehle P, Ekman R (1977) Rapid, simple and specific assays for lipoprotein lipase and hepatic lipase. Artery 3:194–209

    CAS  Google Scholar 

  28. 28.

    Sandholzer C, Saha N, Kark J, Rees A, Jaross W, Dieplinger H, Hoppichler F, Boerwinkle E, Utermann G (1992) Apo (a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler Thromb 12:1214–1226

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Sniderman A, Brown BG, Stewart BF, Cianflone K (1992) From familial combined hyperlipidemia to hyperapoB: unravelling the overproduction of hepatic apolipoprotein B. Curr Opin Lipidol 3:137–142

    CAS  Article  Google Scholar 

  30. 30.

    Teng B, Sniderman AD, Soutar AK, Thompson GR (1986) Metabolic basis of hyperapobetalipoproteinemia. Turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia. J Clin Invest 77:663–672

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Tikkanen M (1990) Practical drug therapy for common hyperlipidaemia. Bailliere's Clin Endocrinol Metab 4:719–742

    CAS  Article  Google Scholar 

  32. 32.

    Warnick GR, Banderson J, Albers JJ (1982) Dextran sulphate-Mg2+ precipitation procedure for quantitation of high density lipoprotein cholesterol. Clin Chem 28:1378–1388

    Google Scholar 

  33. 33.

    Williams KJ, Petrie KA, Brocia RW Swenson TL (1991) Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. J Clin Invest 88:1300–1306

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Wilson DE, Emi M, Iverius P-H, Hata A, Wu LL, Hillas E, Williams RR, Lalouel JM (1990) Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation. J Clin Invest 86:735–750

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Wojciechowski AP, Farrall M, Cullen P, Wilson TME, Bayliss JD, Farren B, Griffin BA, Caslake MJ, Packard CJ, Shepherd J, Thakken R, Scott J (1991) Familial combined hyperlipidaemia linked to the apolipoprotein AI-CIII-AIV gene cluster on chromosome 11q23-q24. Nature 349:161–164

    CAS  Article  PubMed  Google Scholar 

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Correspondence to: M. Seed

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Seed, M., Mailly, F., Vallance, D. et al. Lipoprotein lipase activity in patients with combined hyperlipidaemia. Clin Investig 72, 100–106 (1994).

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Key words

  • Familial combined hyperlipidaemia
  • Lipoproteins
  • Lipoprotein lipase
  • Hepatic lipase