Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies

Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-β-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression of human apoM in LDL receptor-deficient mice reduced the atherogenic effect of a cholesterol-rich diet. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). ApoM was measured in samples from two separate case-control studies. FINRISK '92 consisted of 255 individuals, of whom 80 developed CHD during follow-up and 175 were controls. The Copenhagen City Heart Study included 1,865 individuals, of whom 921 developed CHD during follow-up and 944 were controls. Correlation studies of apoM concentration with several analytes showed a marked positive correlation with HDL and total cholesterol as well as with apoA-I and apoB. There was no significant difference in mean apoM level between CHD and control subjects in either study. In conditional logistic regression analyses, apoM was not a predictor of CHD events, [odds ratio (95% CI) 0.97 (0.74–1.27) and 0.92 (0.84–1.02), respectively]. In conclusion, no association between apoM and CHD could be found in this study. Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-β-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression of human apoM in LDL receptor-deficient mice reduced the atherogenic effect of a cholesterol-rich diet. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). ApoM was measured in samples from two separate case-control studies. FINRISK '92 consisted of 255 individuals, of whom 80 developed CHD during follow-up and 175 were controls. The Copenhagen City Heart Study included 1,865 individuals, of whom 921 developed CHD during follow-up and 944 were controls. Correlation studies of apoM concentration with several analytes showed a marked positive correlation with HDL and total cholesterol as well as with apoA-I and apoB. There was no significant difference in mean apoM level between CHD and control subjects in either study. In conditional logistic regression analyses, apoM was not a predictor of CHD events, [odds ratio (95% CI) 0.97 (0.74–1.27) and 0.92 (0.84–1.02), respectively]. In conclusion, no association between apoM and CHD could be found in this study. Coronary heart disease (CHD) is a major cause of mortality and morbidity. A positive relationship between the concentration of LDL-cholesterol and the risk of CHD has been demonstrated (1Wilson P.W. Garrison R.J. Castelli W.P. Feinleib M. McNamara P.M. Kannel W.B. Prevalence of coronary heart disease in the Framingham Offspring Study: role of lipoprotein cholesterols.Am. J. Cardiol. 1980; 46: 649-654Abstract Full Text PDF PubMed Scopus (239) Google Scholar). Large epidemiological studies have also established an association between an increased risk for CHD and low levels of HDL-cholesterol (2Mensah G.A. Brown D.W. Croft J.B. Greenlund K.J. Major coronary risk factors and death from coronary heart disease: baseline and follow-up mortality data from the Second National Health and Nutrition Examination Survey (NHANES II).Am. J. Prev. Med. 2005; 29: 68-74Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 3Goldbourt U. Yaari S. Medalie J.H. Isolated low HDL cholesterol as a risk factor for coronary heart disease mortality. A 21-year follow-up of 8000 men.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 107-113Crossref PubMed Scopus (332) Google Scholar). The anti-atherogenic properties of HDL are believed to be related to the involvement of HDL in reverse cholesterol transport, a process in which cholesterol is transported from peripheral tissues to the liver (4von Eckardstein A. Nofer J.R. Assmann G. High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport.Arterioscler. Thromb. Vasc. Biol. 2001; 21: 13-27Crossref PubMed Scopus (636) Google Scholar). Apolipoprotein A-I (apoA-I) is the major apolipoprotein of HDL particles, but in addition, HDL also contains several other proteins that have different functions (5Lewis G.F. Rader D.J. New insights into the regulation of HDL metabolism and reverse cholesterol transport.Circ. Res. 2005; 96: 1221-1232Crossref PubMed Scopus (808) Google Scholar, 6Cheung M.C. Albers J.J. Distribution of high density lipoprotein particles with different apoprotein composition: particles with A-I and A-II and particles with A-I but no A-II.J. Lipid Res. 1982; 23: 747-753Abstract Full Text PDF PubMed Google Scholar, 7Gotto Jr., A.M. Pownall H.J. Havel R.J. Introduction to the plasma lipoproteins.Methods Enzymol. 1986; 128: 3-41Crossref PubMed Scopus (284) Google Scholar). ApoM is a 25 kDa, 188 amino acid residue-containing plasma protein that is mainly expressed in liver and kidney (8Xu N. Dahlback B. A novel human apolipoprotein (apoM).J. Biol. Chem. 1999; 274: 31286-31290Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). In the circulation, apoM is preferentially associated with HDL and only to a minor extent with other lipoproteins (8Xu N. Dahlback B. A novel human apolipoprotein (apoM).J. Biol. Chem. 1999; 274: 31286-31290Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar, 9Christoffersen C. Nielsen L.B. Axler O. Andersson A. Johnsen A.H. Dahlback B. Isolation and characterization of human apolipoprotein M-containing lipoproteins.J. Lipid Res. 2006; 47: 1833-1843Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar). In human plasma, apoM is present on approximately 5% of the HDL particles and in less than 2% of the LDL particles (9Christoffersen C. Nielsen L.B. Axler O. Andersson A. Johnsen A.H. Dahlback B. Isolation and characterization of human apolipoprotein M-containing lipoproteins.J. Lipid Res. 2006; 47: 1833-1843Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar). The apoM concentration in human plasma is approximately 0.9 μmol/l (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). A noteworthy feature of apoM is the lack of a signal peptidase cleavage site in the apoM amino acid sequence, explaining why circulating apoM retains its signal peptide (8Xu N. Dahlback B. A novel human apolipoprotein (apoM).J. Biol. Chem. 1999; 274: 31286-31290Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). This unusual property of an extracellular protein is shared with two other HDL-associated proteins, namely paraoxonase-1 and haptoglobin-related protein (11Raper J. Fung R. Ghiso J. Nussenzweig V. Tomlinson S. Characterization of a novel trypanosome lytic factor from human serum.Infect. Immun. 1999; 67: 1910-1916Crossref PubMed Google Scholar). The retained signal peptide of apoM serves as a hydrophobic anchor, binding apoM to the phospholipid layer of the lipoproteins (12Axler O. Ahnstrom J. Dahlback B. Apolipoprotein M associates to lipoproteins through its retained signal peptide.FEBS Lett. 2008; 582: 826-828Crossref PubMed Scopus (43) Google Scholar). Structural analysis and homology modeling have predicted apoM to belong to the lipocalin protein family (13Ahnstrom J. Faber K. Axler O. Dahlback B. Hydrophobic ligand binding properties of the human lipocalin apolipoprotein M.J. Lipid Res. 2007; 48: 1754-1762Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 14Duan J. Dahlback B. Villoutreix B.O. Proposed lipocalin fold for apolipoprotein M based on bioinformatics and site-directed mutagenesis.FEBS Lett. 2001; 499: 127-132Crossref PubMed Scopus (84) Google Scholar). This is supported by the recent finding that apoM binds retinol and retinoic acid in vitro (13Ahnstrom J. Faber K. Axler O. Dahlback B. Hydrophobic ligand binding properties of the human lipocalin apolipoprotein M.J. Lipid Res. 2007; 48: 1754-1762Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar). ApoM-containing lipoprotein particles have been isolated from human plasma and partially characterized (9Christoffersen C. Nielsen L.B. Axler O. Andersson A. Johnsen A.H. Dahlback B. Isolation and characterization of human apolipoprotein M-containing lipoproteins.J. Lipid Res. 2006; 47: 1833-1843Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar). ApoM is associated with a heterogeneous subpopulation of HDL particles. Compared with apoM-free HDL, apoM-containing HDL particles were more efficient in reducing LDL oxidation and in stimulating cholesterol efflux. However, the physiological significance of these findings is uncertain because apoM-containing HDL constitutes only a small portion of total HDL in plasma (9Christoffersen C. Nielsen L.B. Axler O. Andersson A. Johnsen A.H. Dahlback B. Isolation and characterization of human apolipoprotein M-containing lipoproteins.J. Lipid Res. 2006; 47: 1833-1843Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar). The physiological function of apoM is not known, but silencing of apoM expression in mice with small interfering RNA (siRNA) resulted in the accumulation of large, cholesterol-rich HDL particles, due to impaired conversion of HDL to pre-β-HDL (15Wolfrum C. Poy M.N. Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis.Nat. Med. 2005; 11: 418-422Crossref PubMed Scopus (259) Google Scholar). However, in a more recent study of apoM knock-out mice (apoM−/−), the size of HDL in plasma and the amount of plasma pre-β-HDL were not affected in vivo, although the in vitro formation of pre-β-HDL was slightly decreased in apoM−/− mice and increased in human apoM-transgenic mice, as compared with wild-type mice (16Christoffersen C. Jauhiainen M. Moser M. Porse B. Ehnholm C. Boesl M. Dahlback B. Nielsen L.B. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice.J. Biol. Chem. 2008; 283: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar). In both studies, overexpression of apoM in LDL receptor-deficient mice challenged with a cholesterol-rich diet reduced the development of atherosclerosis. These results suggest that apoM plays a role in HDL metabolism and may have anti-atherosclerotic properties (15Wolfrum C. Poy M.N. Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis.Nat. Med. 2005; 11: 418-422Crossref PubMed Scopus (259) Google Scholar, 16Christoffersen C. Jauhiainen M. Moser M. Porse B. Ehnholm C. Boesl M. Dahlback B. Nielsen L.B. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice.J. Biol. Chem. 2008; 283: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar). A 2007 study of three single-nucleotide polymorphisms (SNPs), C-1065A, T-855C, and T-778C, all located in the proximal promoter region of the apoM gene, found that the SNP T-778C was associated with increased levels of plasma total cholesterol and fasting plasma glucose and conferred the risk of development of type 2 diabetes (17Niu N. Zhu X. Liu Y. Du T. Wang X. Chen D. Sun B. Gu H.F. Liu Y. Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese.Diabetes Metab. Res. Rev. 2007; 23: 21-25Crossref PubMed Scopus (50) Google Scholar). A subsequent case-control study showed that CHD patients had an increased frequency of the SNP T-778C allele compared with controls (18Jiao G.Q. Yuan Z.X. Xue Y.S. Yang C.J. Lu C.B. Lu Z.Q. Xiao M.D. A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese.Clin. Biochem. 2007; 40: 1108-1112Crossref PubMed Scopus (33) Google Scholar). The T-855C allele was also recently linked to CHD when carriers of the C allele were found to have an increased risk of CHD compared with the wild-type TT genotype (19Xu W.W. Zhang Y. Tang Y.B. Xu Y.L. Zhu H.Z. Ferro A. Ji Y. Chen Q. Fan L.M. A genetic variant of apolipoprotein M increases susceptibility to coronary artery disease in a Chinese population.Clin. Exp. Pharmacol. Physiol. 2007; 35: 546-551Crossref PubMed Scopus (24) Google Scholar). To be able to expand apoM research to larger human clinical contexts, we have developed a specific quantitative sandwich ELISA for the measurement of apoM in human plasma and (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). Correlation studies between plasma apoM concentration and analytes showed a strong correlation of apoM with plasma total cholesterol (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). The this relationship is not known, but apoM has recently been to be a gene for the receptor liver receptor N. A. J.J. of anti-atherogenic apolipoprotein M gene expression by the receptor Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus (50) Google Scholar). has been as a of that function to cholesterol levels in liver and and is in the control of the acid and reverse cholesterol N. A. J.J. of anti-atherogenic apolipoprotein M gene expression by the receptor Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus (50) Google Scholar, N. B. receptor is a of the Biol. 2006; PubMed Scopus (43) Google Scholar, A. J. S. S. Jr., The receptor the Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). is factor that be because both apoM expression and in cholesterol metabolism (15Wolfrum C. Poy M.N. Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis.Nat. Med. 2005; 11: 418-422Crossref PubMed Scopus (259) Google Scholar). There is a relationship between total plasma cholesterol and the risk of (2Mensah G.A. Brown D.W. Croft J.B. Greenlund K.J. Major coronary risk factors and death from coronary heart disease: baseline and follow-up mortality data from the Second National Health and Nutrition Examination Survey (NHANES II).Am. J. Prev. Med. 2005; 29: 68-74Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, W.B. Castelli W.P. T. McNamara P.M. and the risk of coronary heart The Framingham Med. PubMed Scopus Google Scholar, W.B. D. J. and coronary heart disease mortality in relation to major risk factors in for the Heart J. 1986; PubMed Scopus Google Scholar). The aim of this study was to investigate whether is a relationship between the level of apoM and the risk for apoM was measured in samples from two different frequency case-control studies, the FINRISK '92 a study in a that was for V. V. J. Jauhiainen M. G. Ehnholm C. factors and coronary heart the FINRISK Heart J. PubMed Scopus Google Scholar, J. M. Jauhiainen M. Ehnholm G. factors and lipoprotein in three in the PubMed Scopus Google Scholar, G. J. risk factor in J. 29: PubMed Scopus Google and the Copenhagen City Heart Study in a that was for G. M. The Copenhagen City Heart with data from the Heart J. 2001; Scholar, M. G. J. The Copenhagen City Heart A of with data from the and a follow-up The Copenhagen City Heart Study J. Med. Google Scholar). The study was based on the FINRISK '92 which is a CHD risk factor have been V. V. J. Jauhiainen M. G. Ehnholm C. factors and coronary heart the FINRISK Heart J. PubMed Scopus Google Scholar, J. M. Jauhiainen M. Ehnholm G. factors and lipoprotein in three in the PubMed Scopus Google but in the baseline of the FINRISK '92 was during through samples of and were from the for different in The were to the and to during the The were The follow-up was by a of the study data with the National of and the National the of the study The in these have recently been M. T. M. M. K. of the and of data on coronary heart J. Prev. 2005; PubMed Scopus Google Scholar). In the FINRISK '92 a of analytes as well as diabetes and were from the baseline G. J. risk factor in J. 29: PubMed Scopus Google Scholar, V. V. S. Jauhiainen M. Ehnholm C. J. factors as of coronary and total The FINRISK '92 Thromb. Vasc. Biol. PubMed Scopus (33) Google Scholar). An for this study was that had to be in the from the FINRISK '92 The samples were and had been during when had been for other In the present the were had had an coronary death during the with disease baseline were of the during the of these not the The control subjects were of and the of These were frequency to by and of The is a prospective study of the in with follow-up in and G. M. The Copenhagen City Heart with data from the Heart J. 2001; Scholar, M. G. J. The Copenhagen City Heart A of with data from the and a follow-up The Copenhagen City Heart Study J. Med. Google Scholar). The Copenhagen and the study. were based on the to the the present all were in the follow-up through and with a CHD were and with of CHD and disease during the follow-up clinical and data were for 921 and 944 the in the present were from during the follow-up in of the were with but were not because this not the on of CHD was and by all and in the all of death in the of and from and CHD was as of K. A. T. J. K. of of the of the of Heart J. 1997; PubMed Scopus Google Scholar). A of required the of two of the and of In and plasma samples were in the and samples were A sandwich ELISA for apoM based on two and was to as (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). In the present the of of the ELISA was for the FINRISK '92 samples and for the samples the and had been to levels of total and in both the samples and FINRISK '92 as well as apoA-I and in the samples HDL-cholesterol had been of lipoproteins with and was as the difference between total cholesterol and In the FINRISK all samples were the a of and plasma the level of apoM in is than in plasma, all plasma were to A regression the apoM plasma apoM are by and correlation for and controls correlation of apoM with other risk The association of apoM concentration with coronary was conditional logistic regression and the are expressed for the FINRISK study were for by to the case-control and diabetes were included as in The FINRISK study included developed a CHD during the follow-up and controls. to of apoM levels could be measured in 80 and 175 controls. In the study were the and the controls. The was in both for the FINRISK '92 and Copenhagen City Heart Study subjects included in the with with apolipoprotein are as mean in a apolipoprotein are as mean The study included developed a CHD during the follow-up and controls. ApoM levels and other clinical and data were on 921 and 944 controls. were were The was the and the controls In both studies, the of apoM concentration in the as well as the and controls was not There were no significant in mean apoM concentration between and controls ApoM levels were associated with HDL and total cholesterol for both and controls in both the FINRISK and the samples There were also between apoM levels and apoA-I as well as with in the samples In the was a but significant correlation between and apoM 2 and from correlation studies of apoM with and other with with coronary heart ApoM was by data are from the FINRISK '92 and Copenhagen City Heart Study the in a during follow-up in subjects from FINRISK '92 and the Copenhagen City Heart by and FINRISK also for study and diabetes were included as in to A in a by and FINRISK also for study and diabetes were included as in to A in a (95% (95% (95% (95% expressed by and FINRISK also for study and diabetes were included as in to A in a in a coronary heart ApoM was by data are from the FINRISK '92 and Copenhagen City Heart Study the expressed In conditional logistic regression analyses, apoM was not a predictor of CHD (95% CI) 0.97 in the FINRISK samples and 0.92 in the samples The are In the and diabetes had been as the (95% CI) was for the FINRISK samples and for the samples CHD risk as total and also apoA-I and as significant ApoM is mainly associated with HDL, with present in LDL and (8Xu N. Dahlback B. A novel human apolipoprotein (apoM).J. Biol. Chem. 1999; 274: 31286-31290Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar, 9Christoffersen C. Nielsen L.B. Axler O. Andersson A. Johnsen A.H. Dahlback B. Isolation and characterization of human apolipoprotein M-containing lipoproteins.J. Lipid Res. 2006; 47: 1833-1843Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar). the association with HDL, the concentration of apoM in a strong association with both and LDL-cholesterol as well as with total cholesterol (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). Studies of apoM in mice have suggested apoM to be important for the formation of pre-β-HDL and for the efflux of cholesterol from macrophage foam to HDL (9Christoffersen C. Nielsen L.B. Axler O. Andersson A. Johnsen A.H. Dahlback B. Isolation and characterization of human apolipoprotein M-containing lipoproteins.J. Lipid Res. 2006; 47: 1833-1843Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar, C. Poy M.N. Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis.Nat. Med. 2005; 11: 418-422Crossref PubMed Scopus (259) Google Scholar, 16Christoffersen C. Jauhiainen M. Moser M. Porse B. Ehnholm C. Boesl M. Dahlback B. Nielsen L.B. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice.J. Biol. Chem. 2008; 283: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar). In addition, two of the studies showed that apoM-containing HDL was able to LDL against and the a of oxidation of HDL in mice human is the of HDL and is anti-atherogenic because efflux of cholesterol from macrophage foam cells. overexpression of apoM in LDL receptor-deficient mice challenged with a cholesterol-rich diet suggested apoM to have anti-atherogenic properties (15Wolfrum C. Poy M.N. Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis.Nat. Med. 2005; 11: 418-422Crossref PubMed Scopus (259) Google Scholar, 16Christoffersen C. Jauhiainen M. Moser M. Porse B. Ehnholm C. Boesl M. Dahlback B. Nielsen L.B. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice.J. Biol. Chem. 2008; 283: 1839-1847Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar). These with the relationship between plasma total cholesterol and the risk of development of the present study of association between apoM levels and risk of The samples of the FINRISK study were the study included both plasma and was that the of apoM were approximately in than in This difference is larger than be from the by the that apoM may be from during the as was suggested in a recent study T. C. C. M. The and increases the expression of apoM in LDL in to Med. 2008; PubMed Scopus Google Scholar). The plasma apoM levels in were to the levels of apoM in plasma 0.9 in a study of from the (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). between apoM and total as well as and in both and are in with results (10Axler O. Ahnstrom J. Dahlback B. An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma.J. Lipid Res. 2007; 48: 1772-1780Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar). ApoM was also found to with apoA-I and the major of HDL and in both and controls. In the two conditional logistic regression risk factors as cholesterol and levels were HDL-cholesterol was associated with decreased This that the study was for of risk factors as well as to cholesterol apoM was not found to be a predictor of with of 0.97 and for the FINRISK samples and 0.92 and for the However, be that both studies suggest that the apoM levels are not of the study that of the with a of both and that an association between apoM levels and either which is a of the study. In conclusion, in this case-control although apoM was associated with total and HDL-cholesterol as well as with both apoA-I and no association between apoM and CHD was The to Nielsen and for and for