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 DiseaseLiterature - Christiansen MK, Jensen JM, Nørgaard BL, et al. - JACC Cardiol Img 2017; published online ahead of print
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.’