In this study, lower lifetime risk of coronary heart disease (CHD) in relation to ideal adherence to American Heart Association's Life's Simple 7 (LS7) recommendations was observed for all participants, especially for those with high genetic susceptibility. In Black individuals, adherence to LS7 guidelines contributed to lifetime risk of CHD more so than current polygenic risk scores (PRSs). There is a need for improved PRSs for properly assessing genetic susceptibility for CHD in diverse groups.

• A total of 8,372 White and 2,314 Black participants of the ARIC (Atherosclerosis Risk in Communities) study who were 45 years of age and older and were free of CHD at baseline examination were included to assess remaining lifetime risk and years free of CHD based on polygenic risk and the LS7 guidelines in a population-based cohort study.

• Overall residual lifetime risk was estimated to be 27%, ranging from 16.6% in those with an ideal LS7 score to 43.1% for those with a poor LS7 score.

• Remaining lifetime risk ranged from 19.8% to 39.3% among White participants, by increasing PRS categories.

• A remaining lifetime risk of 67.1% and 15.9 fewer CHD-free years were observed in participants with a high PRS and poor LS7 vs those with intermediate polygenic risk and LS7 scores.

• Ideal LS7 was found to be linked with 20.2 more CHD-free years vs poor LS7, in the high-PRS group.

• Black participants exhibited remaining lifetime risk ranging from 19.1% to 28.6% according to increasing PRS category.

• For participants with poor LS7, similar lifetime risk estimates were obtained irrespective of PRS category.

• In the high-PRS group, an ideal LS7 score was identified to be linked with only 4.5 more CHD-free years than a poor LS7 score.