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CLINICAL STUDIES

Hyperinsulinemic hypoalphalipoproteinemia as a new indicator for coronary heart disease

Keijiro Saku, MD, PhD, FACC^a* , Bo Zhang, MS, PhD^a* , Kazuyuki Shirai, MD, PhD^a* , Shiro Jimi, PhD^*, Kazuhiko Yoshinaga, BS^a* and Kikuo Arakawa, MD, PhD, FACC^a*

^a Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
^* Department of Pathology, Fukuoka University School of Medicine, Fukuoka, Japan
Department of Social Medicine, Fukuoka University School of Medicine, Fukuoka, Japan

Manuscript received March 12, 1998; revised manuscript received June 8, 1999, accepted June 30, 1999.

Reprint requests and correspondence: Dr. Keijiro Saku, Department of Internal Medicine, Fukuoka University School of Medicine, 7-45-1 Nanakuma Jonan-ku, Fukuoka 814-0180, Japan
hh035399{at}msat.fukuoka-u.ac.jp

OBJECTIVES

The purpose of this study was to investigate the association among insulin resistance, high density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD), and to test the hypothesis that HDL-C may ameliorate the adverse effects of insulin.

BACKGROUND

Serum low HDL-C (hypoalphalipoproteinemia) and hyperinsulinemia are independent predictors for CHD, but a strong negative correlation exists between them, as in patients with syndrome X.

METHODS

Fifty-four pairs of cases (M/F: 49/5), defined as patients with angiographically proved CHD, and control subjects (M/F: 49/5) matched with cases with regard to gender and age were included. Insulin resistance was assessed by the homeostasis model assessment (HOMA).

RESULTS

Cases had increased HOMA insulin resistance and lower serum levels of HDL-C than controls. A receiver operating characteristic (ROC) curve analysis indicated that HDL-C and insulin resistance were significant discriminators of CHD (area under ROC curve: 0.72 and 0.69, respectively). The interaction between HDL-C and the association of insulin resistance with CHD was significant: subjects with hyperinsulinemia and high HDL-C had no increased risk of CHD. Multivariate conditional logistic regression analysis showed that hyperinsulinemic hypoalphalipoproteinemia was a stronger indicator for CHD than either HDL-C or insulin resistance alone (–2 log likelihood: 19.0 vs. 12.6 or 15.7).

CONCLUSIONS

Hyperinsulinemic hypoalphalipoproteinemia was a more potent indicator for CHD than either insulin resistance or low serum HDL-C levels alone, and the adverse effects of hyperinsulinemia seem to be ameliorated by high HDL-C levels.

Abbreviations and Acronyms   ANCOVA = analysis of covariance   ANOVA = analysis of variance   apo = apolipoprotein   BMI = body mass index   CHD = coronary heart disease   CI = confidence interval   DM = diabetes mellitus   HDL-C = high density lipoprotein cholesterol   HOMA = homeostasis model assessment   HT = hypertension   ISDN = isosorbide dinitrate   MI = myocardial infarction   PHREG = proportional hazards regression   ROC = receiver operating characteristic   SPECT = single photon emission computed tomography   TC = total cholesterol   TG = triglyceride   VLDL = very low density lipoprotein

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