Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders


      Aims: Apolipoprotein C-III (apoC-III) has been recognized as a useful marker of triglyceride-rich lipoproteins (TRLs) metabolism and proposed as an indicator of prognosis for coronary risk in healthy subjects. We studied cross-sectionally in a population having low cholesterol levels, but a high prevalence of the metabolic syndrome, whether serum levels of total apoC-III or its sub-fractions were independent markers of prevalent coronary heart disease (CHD) or were related to variables reflecting the metabolic syndrome. Methods and results: In 857 unselected participants of the representative population sample of the Turkish Adult Risk Factor Survey in 2001, apoC-III as well as other risk variables were evaluated, and CHD was diagnosed based on clinical findings and Minnesota coding of resting electrocardiograms. The sample consisted of men and women, aged 33–82 years, having a mean waist circumference of 89.4 and 92.9 cm, respectively, 42% of whom had the metabolic syndrome identified by criteria of the ATP III. ApoC-III values were measured by turbidimetric immunoassay. Mean concentrations for non-high-density lipoprotein (nonHDL) apoC-III in men and women were 6.4 and 6.2 mg/dl, respectively, and for apoC-III in HDL were 6.2 and 6.3 mg/dl, respectively. NonHDL apoC-III was similar to, and apoC-III in HDL was higher than that in Western populations. Both fractions of apoC-III were significantly correlated with lipids, lipoproteins, apoB, anthropometric measures, and blood pressures in both genders. Correlations for both were high with serum triglycerides (rs=around 0.70) and apoB (rp=around 0.37). Total apoC-III as well as both fractions were significantly correlated in women also with levels of inflammatory risk markers: strongly (r=0.40–0.45, P<0.001) with complement C3, and weakly (rs=around 0.20, P<0.001) with C-reactive protein. A cutoff of >7.0 mg/dl as opposed to lower levels of nonHDL apoC-III indicated the presence of hypertriglyceridemic hyperapo B with an age-adjusted odds ratio (OR) of 13.8; it indicated the presence of metabolic syndrome with 4.66-fold likelihood. Total apoC-III and nonHDL apoC-III proved to be significantly (P-trend <0.05 and 0.002) and strongly associated with prevalent CHD in men even after adjustment for age, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C): OR gradients across upper and lower quartiles were 3.88-fold (CI: 1.3; 11.4) and 8.8-fold (CI: 2.6; 29.8), respectively. Conclusions: In a population among whom the metabolic syndrome prevails, total- and nonHDL apoC-III are each a determinant in both genders of the metabolic syndrome and of hypertriglyceridemic hyperapo B. Each is a powerful significant marker of prevalent CHD in men independent of LDL- and HDL-C levels. In women, despite being correlated with inflammatory risk markers, the significant association of elevated levels of apoC-III with CHD did not prove to be independent of age.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wang C
        • McConathy W.J
        • Kloer H.U
        • Alaupovic P
        Modulation of lipoprotein lipase activity by apolipoproteins.
        J. Clin. Invest. 1985; 75: 384-390
        • Sacks F.M
        • Alaupovic P
        • Moye L.A
        • Cole T.G
        • Sussex B
        • Stampfer M.J
        • Pfeffer M.A
        • Braunwald E
        VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.
        Circulation. 2000; 102: 1886-1892
        • Hodis H.N
        Triglyceride-rich lipoprotein remnant particles and risk of atherosclerosis.
        Circulation. 1999; 99 (Editorial): 2852-2854
        • Chivot L
        • Mainard F
        • Bigot E
        • et al.
        Logistic discriminant analysis of lipids and apolipoproteins in a population of coronary bypass patients and the significance of apolipoproteins C-III and E.
        Atherosclerosis. 1990; 82: 205-211
        • Luc G
        • Fievet C
        • Arveiler D
        • et al.
        Apolipoproteins C-III and E in apo-B- and non-apo-B-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study.
        J. Lipid Res. 1996; 37: 508-517
        • Uiterwaal C.S.P.M
        • Grobbee D.E
        • Witteman J.C.M
        • et al.
        Postprandial triglyceride response in young adult men and familial risk for coronary atherosclerosis.
        Ann. Intern. Med. 1994; 121: 576-583
        • Ginsberg H.N
        • Jones J
        • Blaner W.S
        • et al.
        Association of postprandial triglyceride and retinyl palmitate responses with newly diagnosed exercise-induced myocardial ischemia in middle-aged men and women.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1829-1838
        • Thompson G.R
        Angiographic evidence for the role of triglyceride-rich lipoproteins in progression of coronary artery disease.
        Eur. Heart J. 1998; 19: H31-H36
        • Blankenhorn D.H
        • Alaupovic P
        • Wickham E
        • et al.
        Prediction of angiographic change in native human coronary arteries and coronary bypass grafts: lipid and nonlipid factors.
        Circulation. 1990; 81: 470-476
        • Mahley R.W
        • Palaoğlu E
        • Atak Z
        • et al.
        Turkish Heart Study: lipids, lipoproteins, and apolipoproteins.
        J. Lipid Res. 1995; 36: 839-859
        • Onat A
        • Yildirim B
        • Uslu N
        • et al.
        Plasma lipoproteins and apolipoproteins in Turkish adults: overall levels, associations with other risk parameters and HDL's role as a marker of coronary risk in women.
        Arch. Turk. Soc. Cardiol. 1999; 27: 72-79
        • Onat A
        Risk factors and cardiovascular disease in Turkey.
        Atherosclerosis. 2001; 156: 1-10
        • 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
        • Rose G
        • Blackburn H
        • Gillum R.F
        • Prineas R.J
        Cardiovascular Survey Methods. 2nd ed. WHO, Geneva1982: 124-127
        • Krauss R.M
        Atherogenicity of triglyceride-rich lipoproteins.
        Am. J. Cardiol. 1998; 81: 13B-17B
        • von Eckardstein A
        • Holz H
        • Sandkamp M
        • Weng W
        • Funke H
        • Assmann G
        Apolipoprotein C-III (Lys58–Glu): identification of an apolipoprotein C-III variant in a family with hyperalphalipoproteinemia.
        J. Clin. Invest. 1991; 87: 1724-1731
        • Marcoux C
        • Tremblay M
        • Fredenrich A
        • Davignon J
        • Cohn J.S
        Lipoprotein distribution of apolipoprotein C-III and its relationship to the presence in plasma of triglyceride-rich remnant lipoproteins.
        Metabolism. 2001; 50: 112-119
        • Batal R
        • Tremblay M
        • Barrett P.H.R
        • et al.
        Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects.
        J. Lipid Res. 2000; 41: 706-718
        • Fredenrich A
        • Giroux L.M
        • Tremblay M
        • Krimbou L
        • Davignon J
        • Cohn J.S
        Plasma lipoprotein distribution of apoC-III in normolipidemic and hypertriglyceridemic subjects: comparison of the apoC-III to apoE ratio in different lipoprotein fractions.
        J. Lipid Res. 1997; 38: 1421-1432
        • Sniderman A
        • Scantlebury T
        • Cianflone K
        Hypertriglyceridemic hyperapo B: the unappreciated atherogenic dyslipoproteinemia in type 2 diabetes mellitus.
        Ann. Intern. Med. 2001; 135: 447-459
        • Krauss R.M
        • Herbert P.M
        • Levy R.I
        • Frederickson D.S
        Further observations on the activation and inhibition of lipoprotein lipase by apolipoproteins.
        Circ. Res. 1973; 33: 403-411
        • Curry M.D
        • McConathy W.J
        • Fesmire J.D
        • Alaupovic P
        Quantitative determination of human apolipoprotein C-III by electroimmunoassay.
        Biochim. Biophys. Acta. 1980; 617: 503-513
        • Kinnunen P.K.J
        • Ehnholm C
        Effect of serum and C apoproteins from very low density lipoproteins on human postheparin plasma hepatic lipase.
        FEBS Lett. 1976; 65: 354-357
        • Van Barlingen H.H
        • de Jong H
        • Erkelens W
        • de Bruin T.W.A
        Lipoprotein lipase-enhanced binding of human triglyceride-rich lipoproteins to heparan sulfate: modulation by apolipoprotein E and apolipoprotein C.
        J. Lipid Res. 1996; 37: 754-763
        • Windler E
        • Havel R.J
        Inhibitory effect of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver.
        J. Lipid Res. 1985; 26: 556-565
        • Clavey V
        • Lestavel-Delattre S
        • Copin C
        • Bard J.M
        • Fruchart J.-C
        Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII and E.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 963-971
        • Mann C.J
        • Toussard A.A
        • Yen F.T
        • et al.
        Inhibitory effects of specific apolipoprotein C-III isoforms on the binding of triglyceride-rich lipoproteins to the lipolysis-stimulated receptor.
        J. Biol. Chem. 1997; 272: 31348-31354
        • Bersot T.P
        • Vega G.L
        • Grundy S.M
        • et al.
        Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population.
        J. Lipid Res. 1999; 40: 432-438
        • Staels B
        • Vu-Dac N
        • Kosykh V.A
        • Saladin R
        • Fruchart J.C
        • Dallongeville J
        • Auwerx J
        Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase: a potential mechanism for the hypolipidemic action of fibrates.
        J. Clin. Invest. 1995; 95: 705-712
        • Bisgaier C.L
        • Essenburg A.D
        • Barnett B.C
        • et al.
        A novel compound that elevates high density lipoprotein and activates the peroxisome proliferator activated receptor.
        J. Lipid Res. 1998; 39: 1317-1330