Differential impact of plasma triglycerides on HDL-cholesterol and HDL-apo A-I in a large cohort

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Abstract

Objectives

To examine the relationship between plasma triglycerides (TG) to HDL-cholesterol (HDL-C) or HDL apo A-I.

Design and Methods

Bivariate and multiple linear regression analyses in a large cohort of 1886 subjects.

Results

Higher plasma TG levels were associated with lower concentrations of both HDL-C and HDL-apo A-I. However, the HDL-C/HDL-apo A-I ratio was inversely correlated with plasma TG indicating that the overall composition of the HDL changed as plasma TG changed. Plasma TG levels contributed to 15.9% of the variance of the HDL-C/HDL-apo A-I ratio, whereas gender, HDL-TG, LDL-TG, body mass index and plasma apo B levels represented between 0.15% and 2.21% of this variance.

Conclusions

These results indicate that increasing levels of plasma TG result in greater reduction in HDL-C levels than in HDL-apo A-I and this might explain, at least in part, the differences that have been observed in the magnitude of the association of HDL-C versus HDL-apo A-I with the risk of cardiovascular disease.

Introduction

By 2020, cardiovascular disease will become the leading cause of death worldwide [1]. The atherogenic lipoproteins- principally LDL- and the antiatherogenic lipoproteins- HDL- account for just over 50% of the population-attributable risk [2]. Currently, HDL-C is used to quantitate HDL. However, apolipoproteins are important components of lipoprotein particles, and there is accumulating evidence that measurement of apo B and apo A-I may improve the prediction of the risk of cardiovascular disease [3], [4], [5], [6], [7].

In humans, there is a strong association between hypertriglyceridemia and lower levels of HDL-C and apo A-I [8], [9], [10], [11]. Little attention has been paid to the relative effects of hypertriglyceridemia on HDL-C versus apo A-I although there was initial evidence, some time ago, that hypertriglyceridemia may be associated with a greater reduction of HDL-C than apo A-I as well as with decreased HDL particle size [12], [13]. There were also data from population studies showing that the correlation between plasma triglycerides was higher to HDL-C than to apoA-I [14]. However, the issue has not been investigated systematically in a dyslipidemic cohort. The objective of the present study, therefore, was to examine HDL composition in a large group of subjects with a wide range of plasma triglyceride levels attending a lipid clinic.

Section snippets

Participants

Data from 1886 consecutive patients seen in consultation between 1995 and 2005 at the Lipid Clinic of the Laval University Medical Center in Québec City were included in this report. Patients ranged in age from 2 years to 86 years. All individuals were instructed to fast at least 12 h before blood samples were drawn and none of these were taken lipid-lowering medications.

Characterization of plasma lipids and lipoproteins

Venous blood samples were obtained from an antecubital vein into Vacutainer tubes containing K3EDTA (1 mg/ml, final

Participants

Data from 1886 participants are presented in this study; 61.5% of these were men with a mean age of 38.9 ± 17.7 years and body mass index (BMI) of 26.5 ± 5.3, and 38.5% were women with a mean age of 39.8 ± 20.1 years and BMI of 25.4 ± 6.1 kg/m2. Table 1 shows the distribution of lipid-lipoprotein profile of the participants. Their mean plasma cholesterol (C) was 6.06 ± 1.52 and the mean plasma triglycerides (TG) were 1.94 ± 1.09 mmol/L. The mean plasma HDL-C, LDL-C, apo B, and HDL-apo AI concentrations

Discussion

In humans, the association between high TG and low HDL-C levels is well known [4], [17], [18]. Moreover, hypertriglyceridemic patients with low HDL-C levels are at greater risk for coronary heart disease (CHD) than those with normal levels [19], although there is considerable evidence this is driven in large part by plasma apo B. Nevertheless, risk is determined as much by HDL as the atherogenic lipoproteins and therefore it is critical to determine how best to measure their concentration. Two

Acknowledgments

This work was supported in part by an operating grant from Heart and Stroke Foundation (Québec). André J. Tremblay is recipient of a HSFC grant. Patrick Couture is recipient of a scholarship from the FRSQ. The authors are grateful to the dedicated staff of the Lipid Research Center. The dedicated work of Mr. G. Cousineau is also acknowledged.

References (42)

  • M.H. Luria et al.

    Cardiovascular risk factor clustering and ratio of total cholesterol to high-density lipoprotein cholesterol in angiographically documented coronary artery disease

    Am. J. Cardiol.

    (1991)
  • N.J. Wald et al.

    Apolipoproteins and ischaemic heart disease: implications for screening

    Lancet

    (1994)
  • M. Naghavi et al.

    From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II

    Circulation

    (2003)
  • I. Bolibar et al.

    Short-term prognostic value of lipid measurements in patients with angina pectoris. The ECAT Angina Pectoris Study Group: European Concerted Action on Thrombosis and Disabilities

    Thromb. Haemost.

    (2000)
  • B. Lamarche et al.

    Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Quebec cardiovascular study

    Circulation

    (1996)
  • P.J. Talmud et al.

    Nonfasting apolipoprotein B and triglyceride levels as a useful predictor of coronary heart disease risk in middle-aged UK men

    Arterioscler. Thromb. Vasc. Biol.

    (2002)
  • M.J. Albrink et al.

    Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population

    Lipids

    (1980)
  • R.J. Deckelbaum et al.

    Plasma triglyceride determines structure-composition in low and high density lipoproteins

    Arteriosclerosis

    (1984)
  • N.R. Phillips et al.

    Serum apolipoprotein A-I levels: relationship to lipoprotein lipid levels and selected demographic variables

    Am. J. Epidemiol.

    (1982)
  • R.J. Havel et al.

    The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum

    J. Clin. Invest.

    (1955)
  • J.J. Albers et al.

    Multi-laboratory comparison of three heparin-Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein

    Clin. Chem.

    (1978)
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