Coronary Plaque Burden and Adverse Plaque Characteristics Are Increased in Healthy Relatives of Patients With Early Onset Coronary Artery Disease

Abstract

Objectives: This study characterized and quantified subclinical atherosclerosis by coronary computed tomography angiography (CTA) in first-degree relatives of patients with early onset coronary artery disease (CAD).

Background: A strong family history of CAD is an important risk factor for adverse cardiovascular events. Whether predisposed individuals suffer an increased burden of coronary atherosclerosis and adverse plaque features is not known.

Methods: We included 88 healthy middle-aged first-degree relatives from 59 families with early onset CAD. Participants were matched by age and sex with 88 control patients with atypical angina or nonanginal chest pain and no family history of CAD, referred for coronary CTA. A blinded analysis of plaque burden and composition was performed using semiautomated plaque quantification software. The relative differences between the median volumes or the odds ratios (OR) were compared between groups, using a mixed model.

Results: First-degree relatives had significantly more affected coronary segments than controls (0 segments: 30% vs. 49%, respectively; 1 to 2 segments: 27% vs. 32%, respectively; 3 to 4 segments: 18% vs. 6%, respectively; and ≥5 segments: 25% vs. 14%, respectively; p = 0.001). In a multivariate model, the relative differences of total plaque, total calcified plaque (CP), total noncalcified plaque (NCP), and total low-density NCP (LD-NCP) were 5.8 (95% confidence interval [CI]: 2.8 to 11.9), 2.6 (95% CI: 1.5 to 4.5), 5.8 (95% CI: 2.9 to 12.0), and 3.6 (95% CI: 2.1 to 6.1), respectively. The adjusted OR of any positive remodeling plaque or any LD-NCP plaque was 4.2 (95% CI: 1.2 to 14) and 4.2 (95% CI: 1.9 to 9.5), respectively.

Conclusions: Healthy first-degree relatives of patients with early onset CAD have an increased coronary plaque burden compared with symptomatic patients. The plaques display characteristics associated with myocardial ischemia and adverse coronary events.

Keywords: atherosclerosis; composition; coronary artery disease; genetic predisposition to disease; multidetector computed tomography; plaque.