Risk of Incident Diabetes and Cardiovascular Diseases: Prevention Opportunities With the American Heart Association’s Life’s Essential 8 in Individuals With Prediabetes Bearing Different Genetic Predisposition

OBJECTIVE: The aim of this research was to investigate the effects of cardiovascular health (CVH), genetic predisposition, and their interactions on new-onset type 2 diabetes (T2D) and cardiovascular diseases (CVD) among individuals with prediabetes. METHOD: We assessed 26,962 individuals with prediabetes from the UK Biobank. Life's Essential 8 (LE8) was utilized to measure CVH. LE8 score encompasses 4 health behaviors (diet, physical activity, nicotine exposure, sleep) and 4 health factors (body mass index, blood lipids, blood glucose, blood pressure). Polygenic risk score (PRS) was utilized to evaluate genetic predisposition. Cox regression analyses were applied to explore the associations of LE8 score and PRS with new-onset T2D, CVD, myocardial infarction (MI), and stroke. RESULTS: Higher LE8 score was associated with lower risk of adverse outcomes (hazard ratios [HRs] ranging from 0.26 to 0.72) after multivariate adjustment. Even a 1-point increment in LE8 score was significantly linked to decreased risk of adverse outcomes in participants with prediabetes (HRs ranging from 0.97 to 0.99). A substantial proportion of incident T2D (70.47%) and CVD (45.12%) cases could be attributable to low LE8 score. Higher PRS was significantly associated with higher risk of adverse outcomes (HRs ranging from 1.38 to 3.68). Compared with those who had a low LE8 score and high PRS, participants with a high LE8 score and low PRS had lower risk of T2D, CVD, MI, and stroke. Participants with low PRS benefited more from adherence to LE8 concerning incident T2D. Besides, further analysis suggested that BMI, blood pressure, and nicotine exposure have the greatest contribution to incident T2D and CVD during the prediabetes stage. CONCLUSIONS: Ideal CVH was associated with lower risk of incident T2D and CVD among individuals with prediabetes, irrespective of their genetic predisposition. If all metrics could not be improved at once, achieving ideal status of BMI and blood pressure and avoiding nicotine exposure should be prioritized.