C-reactive protein levels and prevalence of chronic infections in subjects with hypoalphalipoproteinemia

Abstract

Low levels of high-density lipoprotein cholesterol (HDL-C) show a consistent relationship with the development of atherosclerosis. The underlying mechanisms are not well understood, but recent studies in subjects with primary hypoalphalipoproteinemia suggest that this could represent a proinflammatory condition. To better assess the link between HDL-C levels and C-reactive protein levels and the possible role of chronic infections as putative mediators of this relationship, we studied a population sample with nonselected causes of hypoalphalipoproteinemia. Eighty-six consecutive patients with HDL-C levels below 40 mg/dL who attend our lipid clinic and 86 control subjects with normal concentrations matched for gender, age, smoking habit, and weight were included in the study. Mean HDL-C levels were 34 ± 3.9 and 55.4 ± 8.8 mg/dL for subjects with hypoalphalipoproteinemia and control subjects, respectively. C-reactive protein concentrations were increased in case patients as compared with control subjects (2.13 ± 2.0 vs 1.52 ± 1.8 mg/L; P = .025). The prevalence of herpes simplex virus type 1, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori infections did not differ between the 2 groups. Although a possible confounding variable could be a degree of insulin resistance within the group of patients with low HDL-C levels, our results indicate that C-reactive protein levels are increased in subjects with nonselected hypoalphalipoproteinemia and that chronic infections do not appear to mediate this relationship.

Introduction

Low concentrations of plasma high-density lipoprotein cholesterol (HDL-C) (hypoalphalipoproteinemia) are associated with an increased risk of cardiovascular disease. Data from the Framingham studies suggest that for each 1-mg/dL decrease in HDL-C, the risk of coronary heart disease (CHD) increases by 2% to 4% [1]. Isolated hypoalphalipoproteinemia, low levels of HDL-C and normal low-density lipoprotein cholesterol (LDL-C) concentrations, is the most common lipid abnormality found in young survivors of a myocardial infarction [2], and its prevalence is very high in patients with angiographically documented CHD [3]. The pathophysiological mechanisms involved in this association are not completely understood, but interactions between oxidant activity, reverse cholesterol transport, and, more recently, inflammatory responses have been suggested.

Levels of C-reactive protein (CRP), a sensitive marker of inflammation [4], [5], have been shown to be increased in subjects with primary hypoalphalipoproteinemia, a condition characterized by very low levels of HDL-C. Inflammation [6] and high levels of CRP [7], [8] have been shown to be related to the development of atherosclerosis and cardiovascular events. As such, the hypothesis that follows could be that the connection between hypoalphalipoproteinemia and cardiovascular disease may be mediated, at least in part, by inflammation.

Because most cases of hypoalphalipoproteinemia result from a mixture of secondary causes (eg, hypertriglyceridemia, obesity, sedentary lifestyle, smoking habit, prescribed drugs/medications) or are due to an inherited monogenic or polygenic pattern, we sought to clarify the relationship between low HDL-C and inflammation by measuring the CRP concentrations in consecutive patients with nonselected hypoalphalipoproteinemia who attend our outpatient lipid clinic and by comparing them with the levels in control subjects with normal HDL-C concentrations. Case patients and control subjects were carefully matched for the presence of cardiovascular disease and associated risk factors. Because some existing infections are able to produce low-grade inflammation [9] and influence lipoprotein levels [10], we investigated whether the relationship between CRP and HDL-C could be mediated by concomitant chronic infections.