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FOCUS ISSUE: PLAQUE NEOVASCULARIZATION, HEMORRHAGE, AND VULNERABILITY: ORIGINAL RESEARCH PAPER

Total Cholesterol Content of Erythrocyte Membranes Is Increased in Patients With Acute Coronary Syndrome

A New Marker of Clinical Instability?

Dimitrios N. Tziakas, MD, PhD^_*,1, Juan Carlos Kaski, MD, DSc, FACC^_*,_*, Georgios K. Chalikias, MD, PhD^_*,1, Carlos Romero, MD^,2, Salim Fredericks, PhD, Ioannis K. Tentes, PhD, Alexandros X. Kortsaris, PhD, Dimitrios I. Hatseras, MD, PhD and David W. Holt, PhD

^_* Cardiovascular Biology Research Centre, Division of Cardiac and Vascular Sciences, St. George’s, University of London, London, United Kingdom
Analytical Unit, Division of Cardiac and Vascular Sciences, St. George’s, University of London, London, United Kingdom
University Cardiology Department, Democritus University of Thrace, Alexandroupolis, Greece.

Manuscript received March 14, 2006; revised manuscript received August 14, 2006, accepted August 21, 2006.

^_* Reprint requests and correspondence: Dr. Juan Carlos Kaski, Cardiovascular Biology Research Centre, Division of Cardiac and Vascular Sciences, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. (Email: jkaski{at}sgul.ac.uk).

Objectives: We hypothesized that cholesterol content is increased in the circulating erythrocytes of patients with acute coronary syndrome (ACS) and may be a marker of clinical instability. We therefore sought to investigate whether cholesterol content differs in erythrocyte membranes of patients presenting with ACS compared to patients with chronic stable angina (CSA).

Background: Plaque rupture in ACS depends at least partly on the volume of the necrotic lipid core. Histopathologic studies have suggested that cholesterol transported by erythrocytes and deposited into the necrotic core of atheromatous plaques contributes to lipid core growth.

Methods: Consecutive angina patients were prospectively assessed; 120 had CSA (83 men, age 64 ± 11 years) and 92 ACS (67 men, 66 ± 11 years). Total cholesterol content in erythrocyte membranes (CEM) was measured using an enzymatic assay, and protein content was assessed by the Bradford method.

Results: The CEM (median and interquartile range) was higher (p < 0.001) in ACS patients (184 µg/mg; range 130.4 to 260.4 µg/mg) compared with CSA patients (81.1 µg/mg; range 53.9 to 109.1 µg/mg) (analysis of covariance). Total plasma cholesterol concentrations did not correlate with CEM levels (r = –0.046, p = 0.628).

Conclusions: This study shows, for the first time, that CEM is significantly higher in patients with ACS compared with CSA patients. These findings suggest a potential role of CEM as a marker of atheromatous plaque growth and vulnerability. Large ad hoc studies are required to establish the clinical importance and pathogenic significance of CEM measurement.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACS = acute coronary syndrome   CABG = coronary artery bypass grafting   CAD = coronary artery disease   CEM = total cholesterol content of erythrocyte membranes   CI = confidence interval   CRP = C-reactive protein   HDL = high-density lipoprotein   LDL = low-density lipoprotein   OR = odds ratio   RBC = red blood cell   ROC = receiver-operating characteristics curve

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