High coronary plaque burden in healthy relatives of CAD patients
Coronary Plaque Burden and Adverse Plaque Characteristics Are Increased in Healthy Relatives of Patients With Early Onset Coronary Artery Disease
In first-degree relatives of patients with history of a coronary artery disease (CAD) event already before the 45th year of age, the risk of poor clinical outcomes may be more than 10-fold increased . Plaques causing myocardial ischemia or acute coronary syndrome (ACS) are characterised by the presence of a lipid-rich necrotic core, a low content of calcified material, and extrinsic plaque remodelling . These features can be quantified by CT angiograms (CTA) and can predict clinical outcome, however measurements of subclinical CAD beyond coronary artery calcium (CAC) are rare [3,4].
To evaluate whether a family history of CAD is associated with specific features of coronary atherosclerosis, this study assessed the plaque burden and composition with CTA in 88 relatives with a family history of early onset CAD before their 40th year. This was compared with this of 88 symptomatic control subjects, complaining about atypical angina or non-anginal chest pain.
- Twenty-eight relatives (32%) had multiple affected first-degree family members with early onset CAD. Individuals with familial hypercholesterolemia were excluded. All other patient characteristics were similar between groups.
- When evaluated by systematic coronary risk evaluation (SCORE), 42 relatives (48%) were categorized as low-risk (<1% 10-year risk of a fatal CV event), 42 (48%) were at intermediate-risk (1-4% 10-year risk), while 1 (1%) and 3 (3%) were at high risk (5-9% 10-year risk) and very-high risk (≥10% 10-year risk), respectively.
- In controls, the median pre-test probability of obstructive CAD was 25% (IQR 14-38%).
- The prevalence of CAD was higher in relatives compared with controls; 62 (70%) versus 45 (51%), respectively (P=0.016).
- In relatives, the Agatston scores were higher and CAD was more often associated with the presence of obstructive lesions and proximal locations compared with controls.
- The total plaque volume, total plaque length, and volumes of total calcified plaque (CP), total non-calcified plaque (NCP), and total low-density NCP (LD-NCP) were significantly higher in relatives.
- Relatives were more likely to have 1 or more plaques with positive remodeling (crude OR 2.4, 95% CI 1.3-4.5, P=0.004; adjusted OR 4.2, 95% CI 1.2-14.0, P=0.021) as well as 1 or more plaques containing LD-NCP (crude OR 2.5, 95% CI 1.3-5.0, P=0.008; adjusted OR 4.2, 95% CI 1.9-9.5, P=0.001).
Healthy relatives of patients with CAD onset before the age of 40 have a high coronary plaque burden and display more unfavourable plaque features compared with symptomatic patients without family history. These findings may provide a better understanding of the inheritance of CAD.
In their editorial article , Khera and Joshi note: ‘A major enhancement in this study was going beyond quantification of calcified and noncalcified plaque but also investigating additional high-risk parameters of plaque composition and vessel characteristics.’ They also point out some study limitations, including:
- A bias to study results was the selection of a symptomatic control group.
- The cut-off age of 40 years is particularly low and not a standard threshold age.
- The diagnostic criteria for excluding familial hypercholesterolemia are not provided.
- One-third of relatives had more than one family members with very early CAD.
The authors conclude: ‘Whether the addition of coronary CTA information, including markers of vulnerable plaque such as LD-NCP or positive remodeling, adds incremental prognostic value for CHD risk assessment in those with a family history of CHD is unanswered in this study. As such, broad screening for coronary atherosclerotic plaque or vulnerable plaque using coronary CTA in those with a family history cannot be advocated at this time. However, this study certainly adds to the picture of what lies beneath a malignant family history of CHD.’