Impact of cardiovascular health and genetic risk on coronary artery disease in Chinese adults

Abstract

ObjectiveTo examine whether adherence to ideal cardiovascular health (CVH) can mitigate the genetic risk of coronary artery disease (CAD) in non-European populations.MethodsFine and Grey’s models were used to calculate HRs and their corresponding 95% CIs, as well as the lifetime risk of CVH metrics across Polygenic Risk Score (PRS) categories.ResultsWe included 39 755 individuals aged 30–75 years in Chinese prospective cohorts. 1275 CAD cases were recorded over a mean follow-up of 12.9 years. Compared with unfavourable CVH profile (zero to three ideal CVH metrics), favourable CVH profile (six to seven ideal CVH metrics) demonstrated similar relative effects across PRS categories, with the HRs of 0.40 (95% CI 0.24 to 0.67), 0.41 (95% CI 0.32 to 0.52) and 0.36 (95% CI 0.26 to 0.52) in low (bottom quintile of PRS), intermediate (two to four quintiles of PRS) and high (top quintile of PRS) PRS categories, respectively. For the absolute risk reduction (ARR), individuals with high PRS achieved the greatest benefit from favourable CVH, mitigating the risk to the average level of population (from 21.1% to 8.7%), and the gradient was strengthened in individuals at the top 5% of PRS. Moreover, compared with individuals at low PRS, those at high PRS obtained longer CAD-free years (2.6 vs 1.1) from favourable CVH at the index age of 35 years.ConclusionFavourable CVH profile reduced the CAD relative risk by similar magnitude across PRS categories, while the ARR from favourable CVH was most pronounced in high PRS category. Attaining favourable CVH should be encouraged for all individuals, especially in individuals with high genetic susceptibility.

Genetic Predisposition, Sedentary Behavior, and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study

“…Specifically, participants with ST <6 h·d −1 were associated with a 53% lower relative risk and 1.90% lower absolute risk of incident CAD than those with ST ≥10 h·d −1 . Similar patterns of ARR among different genetic risks were also noted from other favorable lifestyle behaviors, including brisk walking, no current smoking, no obesity, regular physical activity, and a healthy diet (12,24,30). For example, the UK Biobank study reported a greater reduction in absolute 10-yr risk of CAD related to brisk walking among participants at high genetic risk than low genetic risk (12).…”

Cardiovascular risk assessment: The key path toward precision prevention

“…For example, polygenic risk determines the patterns of blood lipid changes, and individuals at high polygenic risk show the greatest annual changes toward unfavorable lipid profiles and require intensive lifestyle intervention 20 . Furthermore, adherence to cardiovascular health metrics could mitigate the genetic risk, and individuals with high genetic susceptibility would gain greater lifetime risk reductions 21,22 . Thus, the PRS can be used to identify target populations and guide early lifestyle management to alleviate or even reverse their risks from a high genetic background.…”

“… 20 Furthermore, adherence to cardiovascular health metrics could mitigate the genetic risk, and individuals with high genetic susceptibility would gain greater lifetime risk reductions. 21 , 22 Thus, the PRS can be used to identify target populations and guide early lifestyle management to alleviate or even reverse their risks from a high genetic background. Moreover, incorporating the polygenic risk into conventional cardiovascular risk could further refine the risk stratification for CVD within each clinical risk stratum and provide useful risk stratification recommendations for identifying patients who should be initiated or administered intensive lifestyle changes and/or drug treatments.…”

Polygenic risk, lifestyle and the lifetime risk of coronary artery disease

“…Their PRS does leverage the largest, predominantly European ancestry GWASs, but also leverages GWASs in 51 531 CAD cases and 215 934 controls from East Asia, including China, Japan and Malaysia. In the current issue, Cui et al use this score to investigate the interplay between polygenic risk and adherence to ideal cardiovascular health in Chinese adults 8. The importance of performing such research in different populations is underscored by the attributes of the study population: lifetime risk of CAD events is lower in the Chinese population than in the previously studied European and African ancestry populations, while the prevalence of poor adherence to cardiovascular health is higher.…”

“…Lifetime risk of coronary artery disease (CAD) according to favorable, intermediate, or unfavorable adherence to cardiovascular health across various polygenic risk score (PRS) categories in Chinese adults, as estimated by Cui et al 8 Figure adapted from Cui et al (reproduced with permission, BMJ Publishing Group, Copyright 2022). The cumulative risk of CAD by age of 80 years was estimated by Fine and Gray’s proportional hazards model with age as the time scale and adjusted for sex, cohorts and the first four principal components.…”