Abstract MP34: Association of Biological Age Acceleration With Incident Type 2 Diabetes and Coronary Artery Disease

Abstract

Introduction: Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status and prediction of cardiometabolic disease mortality. Genetics play an important role in the pathogenesis of type 2 diabetes (T2D) and coronary artery disease (CAD). However, the associations of BA acceleration with incident T2D and CAD as well as how the interactions between genetic risk and BA acceleration implicate in the development of these two diseases remain unclear. Hypothesis: We hypothesized that BA acceleration was significantly associated with incident T2D and CAD. We further hypothesized that there were significant interactions between BA acceleration and genetic risk in relation to risk of T2D and CAD. Methods: This prospective cohort study utilized data from the UK Biobank. BA was quantified by KDM-BA and PhenoAge, two composite measures derived from blood chemistry and physical examination data. T2D and CAD were diagnosed using self-reported medical history, medication, and hospital inpatient records. Multivariable Cox proportional hazard models were employed to estimate the associations of BA acceleration with incident T2D and CAD. A polygenic risk score (PRS) for T2D or CAD divided into tertiles was used to assess the interactions between BA acceleration (divided into quartiles) and genetic risk with regards to the development of T2D and CAD. Derived estimates were hazard ratios (HRs) and their 95% confidence intervals (CIs) per one standard deviation increment in each of the two BA measures. Results: This study analyzed 271,855 participants without T2D and 267,293 participants without CAD at baseline. Over a median follow-up time of 14.6 and 14.5 years, 9,562 incident T2D events and 18,509 incident CAD events occurred, respectively. Individuals with greater BA acceleration were at increased risk of T2D (HR for KDM-BA: 1.42, [95% CI: 1.39-1.46]; HR for PhenoAge: 1.23, [95% CI: 1.20-1.25]). Similarly, BA acceleration was significantly associated with a higher risk of CAD (HR for KDM-BA: 1.22, [95% CI: 1.20-1.25]; HR for PhenoAge: 1.12, [95% CI: 1.10-1.14]). People with greater genetic risk and BA acceleration had higher risks of T2D and CAD (P for interaction < 0.002). Compared with participants with the lowest level of PRS and BA acceleration, those with the highest level of PRS and BA acceleration had a higher risk of developing T2D (HR for KDM-BA: 7.03, [95% CI: 6.16-8.02]; HR for PhenoAge: 6.39, [95% CI: 5.38-7.58]) and CAD (HR for KDM-BA: 2.83, [95% CI: 2.62-3.06]; HR for PhenoAge: 2.27, [95% CI: 2.09-2.46]). Conclusions: BA acceleration was significantly associated higher risks of T2D and CAD, especially among individuals with a high genetic predisposition to T2D and CAD.