Genetic factors comparable to stroke, diabetes in development of CAD

First-degree relatives of patients with early onset coronary artery disease (CAD) had nearly six times the amount of total coronary plaque when compared to age-matched, symptomatic controls, putting them at increased risk of adverse cardiac events, according to a new study from Denmark.

Via CT angiography, researchers identified 70 percent of relatives as having some level of coronary plaque versus 51 percent of controls, all of whom had atypical angina or nonanginal chest pain and no family history of CAD. Fifteen percent of the relatives were found to have obstructive plaque compared to 10 percent of controls.

The authors noted in JACC: Cardiovascular Imaging the differences might have been more extreme had they chosen asymptomatic controls.

“The extent of CAD in relatives was remarkable,” wrote the authors, including lead researcher Morten K. Christiansen, MD, from the department of cardiology at Aarhus University Hospital, where the trial was conducted.

“The present findings indicate that the risk of CAD associated with a genetic predisposition is comparable to the risk conveyed by known risk factors such as diabetes, familial hypercholesterolemia, and stroke.”

Patients who had undergone PCI or coronary artery bypass grafting before the age of 40 were asked to recruit first-degree relatives—parents, siblings and children—who were between 30 and 65 years old. Those relatives were only included in the study if they weren’t obese and had no history of atrial fibrillation or CAD.

The final study group included 88 relatives and 88 symptomatic controls who were matched by age and gender. The mean age was 47.8 years and 53 percent of participants were men.

Eighteen percent of the relatives had three or four affected coronary segments compared with 6 percent of the control group. In addition, 25 percent of the family members had at least five affected segments versus 14 percent of controls.

Christiansen and colleagues suggested similar lifestyles among family members, in addition to genetic predisposition, could partially explain the results.

In an accompanying editorial, Amit Khera, MD, and Parag Joshi, MD, pointed out the researchers’ age threshold of 40 for coronary revascularization could have overpowered the findings. This threshold is lower than previous studies regarding family history, they said, and likely represents more extreme predisposition to CAD in the initial patients and their relatives.

Still, the study reinforced the importance of documenting a complete family history of CAD “at every clinical encounter,” Khera and Joshi wrote.

“The clinical relevance of a family history of CHD (coronary heart disease) is frequently underappreciated, particularly in women,” they continued. “Also, rather than a binary construct, there are gradations of family history, with especially malignant family histories involving multiple affected first-degree relatives or those at unusually young ages. In select individuals, screening for subclinical atherosclerosis, typically with coronary calcium scanning if it will impact treatment decisions, may be considered as the results may provide additive and incremental information for CHD risk.”