A genetic risk score (GRS) was found to be useful in identifying young individuals at high risk for coronary heart disease (CHD) who need to undergo coronary artery calcium (CAC) screening, according to a study published in the Journal of the American College of Cardiologists: Cardiovascular Imaging.

In this study, data from 5115 healthy Americans of European or African descent recruited between 1985 and 1986 to participate in the Coronary Artery Risk Development in Young Adults study, were analyzed. Participants (n=1927) were assessed at 15 years with computed tomography. These data were combined with genotype data from the Multi-Ethnic Study of Atherosclerosis study, which included 6660 Americans of European, African, Chinese, or Hispanic ancestry. GRS was calculated based on the presence/absence of 142 single nucleotide polymorphisms associated with the occurrence of CHD events.

GRS did not differ within European (P =.33) or African (P =.73) ancestral cohorts. The only traditional risk factor for CHD which correlated with GRS was family history (P =.017) and trended toward significance for low-density lipoprotein cholesterol (LDL-C) concentration among European Americans (slope, 1.51 mg/dl per standard deviation [SD] of GRS; P =.088).


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CAC was more prevalent among men vs women (17.2% vs 6.4%, respectively; P =1.3×1013). Men, but not women, with high vs low GRS had higher CAC (men: 24.1% vs 12.1%, respectively; women: 5.6% vs 6.1%, respectively).

The risk for CAC increased with GRS (odds ratio [OR], 1.33 for each GRS SD increase from mean GRS [3.31±01.83]; 95% CI, 1.26-1.40; P <2×1016) in a model in which sex and age were taken into account. This OR was 1.28 (95% CI, 1.21-1.36; P <2×1016) when additional clinical variable were also accounted for (eg, LDL-C).

According to the latter model, women with a GRS  2 SD higher than the population mean should undergo a CAC scan at age 50.5 years (95% CI, 49.2-51.8 years), and those with a GRS 2 SD lower than the population mean should get their first scan at age 61.6 years (95% CI, 60.4-62.9 years). For men with higher and lower than average GRS, the scan should be performed at ages 40.2 years (95% CI, 38.7-41.5 years) and 51.3 years (95% CI, 50.0-52.6 years), respectively.

Individuals of European vs African descent with high GRS were recommended to have scans at younger ages (Europeans: women, 50.7 years; men, 39.3 years; Africans: women, 53.5 years; men, 44.5 years).

The addition of GRS to traditional CHD risk factors was found to improve the prediction of CAC among women aged 44 to 54 years (continuous net reclassification improvement [NRI], 0.363; 95% CI, 0.218-0.512), women aged 50 to 60 years (NRI, 0.263; 95% CI, 0.049-0.477), men aged 34 to 44 years (NRI, 0.325; 95% CI, 0.187-0.476), and men aged 40 to 50 years (NRI, 0.325; 95% CI, 0.187-0.476).

This study may have been biased due to the reliance on CAC assessment at a single time point.

“The GRS improves risk stratification for CAC presence over the lifetime when incorporated with traditional risk factors,” concluded the study authors.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Severance L M, Carter H, Contijoch F J, et al. Targeted Coronary Artery Calcium Screening in High-Risk Younger Individuals Using Consumer Genetic Screening Results. JACC Cardiovasc Imaging. 2021;S1936-878X(20)31020-2. doi:10.1016/j.jcmg.2020.11.013