The clinical relevance of dysfunctional HDL in patients with coronary artery disease: A 3-year follow-up study

Abstract

The well known atheroprotective effects of high density lipoprotein cholesterol (HDL) are based on reverse cholesterol transport as well as anti-inflammatory properties [1,2]. Primary prevention studies have confirmed that HDL levels are strongly associated with reduced cardiovascular events [3]. However, recent evidence supports the notion that HDL functionality may be impaired under certain conditions [4,5]. Ansell and colleagues reported that HDL isolated from subjects with coronary artery disease (CAD) had less antiinflammatory activity than HDL derived from healthy controls, thus providing the first evidence that HDL may be dysfunctional in this setting [6]. Interestingly, in CAD patients HDL has shown to be even proinflammatory, thus increasing monocyte chemiotaxis, reactive oxygen species production, endothelial dysfunction and cellular apoptosis [6,7]. Hence, HDL may not be protective in secondary prevention of coronary artery disease. This issue needs to be rapidly clarified since therapies that raise HDL levels are being investigated for the treatment of CAD patients [8,9]. In the present study we sought to determine whether higher HDL levels maintain their protective effects also in patients with CAD. From March 2006 to April 2009 we consecutively enrolled 184 patients with a first manifestation of CAD (mean age 62±10 years, male/female ratio 3:1). All patients taking lipid-lowering agents or other cardiovascular medications at admission were excluded from the study. Moreover, patients with relevant comorbidities (renal failure, COPD, infective or inflammatory diseases, autoimmune disorders, cancer) were also not considered. All subjects underwent coronary angiography and routine blood chemistry including high sensitivity C-reactive protein (hs-CRP) and lipid profile comprehensive of ApoB-100 and ApoA1 determination. The study was approved by our Institute Committee and all patients signed an informed consent. The study population was divided into groups with higher (N50 for women, N40 formen) and lower HDL levels (≤50 for women, ≤40 for men, Table 1), according to ATPIII criteria [10]. Groups did not significantly differ for demographic and antropometric characteristics as well as for the prevalence of cardiovascular risk factors and left ventricular ejection fraction (EF). Serum creatinine, fasting plasma glucose, uric acid and Pro-BNP were similar in the two groups. HDL and ApoA1 were significantly different but the groups did not differ with regard to LDL and ApoB-100 levels (Table 1). Patients with high HDL had significantly lower triglycerides and hs-CRP values (Table 1). Notably, statin treatment and dose were similar between the two groups (Table 2). Cardiovascular end-points were assessed by clinic visits and programmed phone contacts up to 3 years after the first admission. Determinations of lipid fractions were performed both at baseline and follow-up. No significant changes in HDL levels were observed during follow-up either in patients with high or low HDL (Fig. 1A,B). Major adverse cardiovascular events (MACE) consisted of: (1) mortality for all causes; (2) myocardial infarction (MI); (3) revascularization by percutaneous coronary intervention or by-pass surgery; (4) cerebrovascular events including transient ischemic attack and stroke. Data analysis was performed with SPSS 13.0 software package (SPSS Inc., Chicago). Numerical data are reported as