Elsevier

Atherosclerosis

Volume 199, Issue 2, August 2008, Pages 402-407
Atherosclerosis

Prevalence and determinants of coronary artery disease in males and females with familial combined hyperlipidaemia

https://doi.org/10.1016/j.atherosclerosis.2007.11.021Get rights and content

Abstract

Background

Familial combined hyperlipidaemia (FCH) is an inherited dyslipidaemia that is related to a high risk of coronary artery disease (CAD). We evaluated the prevalence of CAD in a large FCH population and the association of risk factors with CAD according to gender.

Methods

In this single-center, observational study, lipid and lipoprotein variables were measured in untreated patients with FCH (565 males and 302 females). CAD was defined as a documented history of myocardial infarction or coronary revascularization, or an abnormal coronary angiogram (stenosis of >50% in an epicardial coronary artery), or angina plus abnormal imaging stress test.

Results

Males had higher triglyceride level (P < 0.001) but lower total cholesterol (P < 0.001) and HDL-cholesterol level (P < 0.001) compared to women. The prevalence of CAD was 22.2% in men and 4.6% in women (P < 0.001). In logistic regression analysis, male gender was associated with a higher risk of CAD independent of lipid parameters and other risk factors (adjusted ORs for CAD 9.4, P < 0.001). In gender-specific analysis, age (OR = 1.06 per 1-year increase, P < 0.001), diabetes (OR = 2.42, P < 0.01) and Lp(a) (OR = 1.09 per 1-mg/dL increase, P < 0.01) were independent predictors of CAD in men. In women, age (OR = 1.24, P < 0.01), total cholesterol (OR = 1.022 per 1-mg/dL increase, P < 0.05) and fasting glucose (OR = 1.031 per 1-mg/dL increase, P < 0.05) were independently associated with CAD.

Conclusions

In FCH patients, the prevalence of CAD is higher in males than in females, independent of lipidaemic profile and other risk factors. Among lipid variables, Lp(a) and cholesterol level are predictors of CAD in males and females respectively.

Introduction

Familial combined hyperlipidaemia (FCH) is a common heritable lipid disorder with a prevalence of 0.5–2% in the general population [1], [2], [3], [4]. FCH is characterized by hypercholesterolaemia and/or hypertriglyceridaemia, low level of high-density lipoprotein (HDL)-cholesterol, high levels of apolipoprotein B (apoB) and atherogenic small dense low-density lipoprotein (LDL) particles and increased rates of metabolic abnormalities such as obesity, diabetes and metabolic syndrome [1], [2], [3]. Importantly, several epidemiological studies indicate that FCH is associated with an increased risk of premature coronary artery disease (CAD) [1], [4], [5], [6]. In particular, the prevalence of CAD in FCH patients younger than 60 years is estimated to be as high as 20% [2].

It is established that male gender is a major risk factor for atherosclerotic cardiovascular disease [7], as the prevalence of CAD is higher in men compared to women of same age. However, the protective effect of female gender is blunted after the menopause [8].

Data regarding the prevalence of CAD according to gender in FCH patients are limited. Furthermore, there is no sufficient evidence to indicate the contribution of lipids or non-lipid risk factors to the development of CAD in men and women with FCH. Accordingly in this single-center, observational study, we sought to investigate the prevalence and determinants of CAD in a large population of males and females with FCH.

Section snippets

Study population and design

In this study, we enrolled a total of 867 patients with FCH (565 males, mean age 45.8 ± 11.0 and 302 females, mean age 53.9 ± 9.2), who had been referred to our lipid outpatient clinic during the last 20 years (1987–2006). All subjects were Caucasians and were not taking any hypolipidaemic drug (never-treated patients or untreated patients for ≥3 months). In all participants, a complete medical history was obtained and detailed physical examination was performed.

Systolic and diastolic blood

Clinical characteristics, lipids and risk factors according to gender

Clinical characteristics of the study population according to gender are shown in Table 1. Males with FCH were younger (P < 0.001) and more obese than women (higher BMI and waist-to-hip ratio, P < 0.05 and P < 0.001, respectively) and had a higher prevalence of smoking (P < 0.001). Both genders had similar prevalence of hypertension, diabetes and metabolic syndrome (P = NS).

Lipid variables according to gender

Lipid values in men and women are shown in Table 1. Women had higher levels of total cholesterol, LDL-cholesterol, apolipoprotein B

Discussion

To our knowledge, this is the first study to comparatively evaluate anthropometric characteristics, cardiovascular risk factors and the prevalence and predictors of CAD in a large population with FCH, according to a gender-related approach. Our results indicate that the prevalence of overt CAD is almost five-fold higher in FCH men compared to older, predominantly postmenopausal FCH women. This association between male gender and CAD is independent of anthropometric characteristics, lipid levels

Acknowledgements

Conflicts of interest: None.

Funding sources: None.

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