Serum Total and High-Density Lipoprotein Phospholipid Levels in a Population-Based Study and Relationship to Risk of Metabolic Syndrome and Coronary Disease

Abstract

The aim of study was to investigate the role of serum total (TPL) and high-density lipoprotein phospholipids (HDL-pl) as a risk factor in coronary heart disease (CHD) and metabolic syndrome (MS). In a random sample, total and HDL-pl were measured in 1088 and 642 adults from Turkey, respectively, who have a high prevalence of MS; this was done with an enzymatic method that measures total phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine. Serum TPL and HDL-pl levels were significantly higher in women (TPL, 2.8 mmol/L; HDL-pl, 1.21 mmol/L) than in men. Strong correlations existed between serum TPL levels and non-HDL cholesterol (HDL-C), triglycerides, apolipoprotein (apo) B, complement C3, and γ-glutamyltransferase. Non—HDL-C, HDL triglyceride, and apo A-I were strongly correlated with HDL-pl. Linear regression analyses revealed HDL-C, apo B, triglycerides, diabetes, and female gender as independent significant determinants of TPL levels in adults. HDL-C and impaired glucose regulation were sole significant variables, together contributing one-quarter of serum HDL-pl. Individuals with MS or diabetes had significantly higher TPL concentrations. The gender- and age-adjusted odds ratio (OR) of TPL for MS was 1.73 (95% confidence interval, 1.35-2.21), whereas the multiadjusted OR of HDL-pl per 1 SD increment corresponded to a significantly reduced independent MS likelihood by 26% in women (and 18% in the entire group). The multiadjusted OR of HDL-pl for CHD in men and women combined was 0.32 (P = .057) corresponding to a reduced CHD likelihood by 32% per 1 SD increment of HDL-pl. Plasma TPL levels point to an adverse relationship to MS, whereas their role in CHD risk needs further investigation. HDL-pls, in contrast, mark substantial protection from MS as well as from CHD.

Keywords

phospholipids population-based study coronary heart disease metabolic syndrome

Get full access to this article

View all access options for this article.

References

Tabas I. Lipids and atherosclerosis. In: Bernardi G , Vance DE , Vance JE , eds. Biochemistry of Lipids, Lipoproteins and Membranes . 4th ed. Amsterdam, Holland: Elsevier; 2002 :573-559.

Kitchens RL , Thompson PA , Mundford RS , O' Keefe GE Acute inflammation and infection maintain circulating phospholipid levels and enhance lipopolysaccharide binding to plasma lipoproteins. J Lipid Res. 2003;44:2339-2348.

Vance JE Assembly and secretion of lipoproteins. In: Bernardi G , Vance DE , Vance JE , eds. Biochemistry of Lipids, Lipoproteins and Membranes. 4th ed. Amsterdam, Holland: Elsevier; 2002 :505-526.

Merill AH , Sandhoff K. Sphingolipids: metabolism and cell signalling. In: Bernardi G , Vance DE , Vance JE , eds. Biochemistry of Lipids, Lipoproteins and Membranes. 4th ed. Amsterdam, Holland: Elsevier ; 2002 :373-407.

Jian B. , de la Llera-Moya M. , Royer L. , Rothblat G. , Francone O. , Swaney JB Modification of the cholesterol efflux properties of human serum by enrichment with phospholipid. J Lipid Res. 1997;38:734-744.

Subbaiah PV Determination and clinical significance of phospholipids. In: Rifai N , Warnick GR , Dominiczak MH , eds. Handbook Lipoprotein Testing . Washington, D.C.: AACC Press; 1997:415-427.

Fournier N. , de la Llera Moya M. , Burkey BF , et al. Role of HDL phospholipid in efflux of cell cholesterol to whole serum: studies with human apoA-I transgenic rats. J Lipid Res. 1996;37:1704-1711.

Fournier N. , Atger V. , Cogny B. , et al. Analysis of the relationship between triglyceridemia and HDL-phospholipid concentrations: consequences on the efflux capacity of serum in the Fu5AH system. Atherosclerosis. 2001;157:315-323.

Cui Z. , Houweling M. Phosphatidylcholine and cell death. Biochim Biophys Acta. 2002;1585:87-96.

10.

Onat A. , Ceyhan K. , Basar Ö. , Erer B. , Toprak S. , Sansoy V. Metabolic syndrome: major impact on coronary risk in a population with low cholesterol levels: a prospective and cross-sectional evaluation . Atherosclerosis. 2002;165: 285-292.

11.

Onat A. , Hergenç G. , Uzunlar B. , et al. Serum total phospholipids in Turkish adults: a cross-sectional study on associations with risk of metabolic syndrome and coronary disease . Arch Turk Soc Cardiol. 2004;32:168-177.

12.

Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

13.

Takayama M. , Itoh S. , Nagasaki T. , Tanimuzu I. A new enzymatic method for the determination of serum choline—containing phospholipids. Clin Chim Acta. 1977;79:93-98.

14.

American Diabetes Association : clinical practice recommendations. Diabetes Care. 1997;20:1-70.

15.

Friedewald WT , Levy RI , Fredrickson DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge . Clin Chem. 1972;18:499-509.

16.

Rose G. , Blackburn H. , Gillum RF , Prineas RJ Cardiovascular Survey Methods. 2nd ed. Geneva, Switzerland: World Health Organization ; 1982: 124-127.

17.

Eisenberg S. High density lipoprotein metabolism. J Lipid Res. 1984;25:1017-1058.

18.

Kitchens RL , Thompson PA , Munford RS , O'Keefe GE Acute inflammation and infection maintain circulating phospholipid levels and enhance lipopolysaccharide binding to plasma lipoproteins. J Lipid Res. 2003;44:2339-2348.

19.

Leitinger N. Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr Opin Lipidol. 2003 ;14:421-430.

20.

Piperi C. , Kalofoutis C. , Papaevangeliou D. , Papapanagiotou A. , Lekakis J. , Kalofoutis A. The significance of serum HDL phospholipid levels in angiographically defined coronary artery disease. Clin Biochem. 2004 ; 37:377-381.

21.

Kunz F. , Pechlaner C. , Erhart R. , Fend F. , Muhlberge V. HDL and plasma phospholipids in coronary artery disease. Arterioscler Thromb Vasc Biol. 1994;14: 1146-1150.

22.

Horter MJ , Sondermann S. , Reinecke H. , et al. Associations of HDL phospholipids and paraoxonase activity with coronary heart disease in postmenopausal women. Acta Physiol Scand. 2002;176:123-130.

23.

Fournier N. , Paul JL , Atger V. , et al. HDL phospholipid content and composition as a major factor determining cholesterol efflux capacity from Fu5AH cells to human serum. Arterioscl Thromb Vasc Biol . 1997;17:2685-2691.

24.

Leventhal AR , Chen W. , Tall AR , Tabas I. Acid sphingomyelinase-deficient macrophages have defective cholesterol trafficking and efflux. J Biol Chem. 2001; 276:44976-44983.

25.

Bolin DJ , Jonas A. Sphingomyelin inhibits the lecithin-cholesterol acyltransferase reaction with reconstituted high density lipoproteins by decreasing enzyme binding . J Biol Chem. 1996;271:19152-19158.