Abstract 009: Association of Accelerated Biological Aging in Midlife with Cardiovascular and Health Outcomes in the Framingham Offspring Study

Introduction: Biological age acceleration (BAA) constructed from multi-organ system biomarkers may better elucidate the aging process relative to chronological age (CA). We evaluated the association of BAA with long-term health outcomes among middle-aged adults. Hypothesis: We related mid-life accelerated BA to the incidence of death, CVD, and dementia. Methods: We modeled BAA using multiple biomarkers (anthropometric and biochemical indicators of vital organ systems) at the sixth examination cycle (1995-1998) for up to 2038 Framingham Offspring participants. Stratified by sex, we estimated BA using the Klemera and Doubal method (KDM) with principal components. Standardized residuals from regressing KDM-BA on CA were used to define accelerated BA (>1 SD), moderate BA ([-1 to 1 SD]), and slow BA (<-1 SD; referent). Utilizing multivariable-adjusted Cox proportional hazards and competing risk models, we related BAA to incident death, CVD, and dementia. Results: Over a median follow-up of 24 years (max 27 years), participants (mean age 57 years, 57% women) experienced 656 deaths, 454 new-onset CVD events, and 170 incident dementia outcomes. Men and women with accelerated BA had a 2.1-fold (95%CI [1.40-3.21]; p=0.0004) and a 1.7-fold higher risk for death (95%CI [1.10-2.55]; p=0.02), respectively, compared to the referent group. Women with accelerated BA had a 1.8-fold higher risk of CVD (95%CI [1.12-2.90]; p=0.02) compared to slow BA. Higher BAA was associated with a higher dementia risk (HR per SD-increase 1.25, 95%CI [1.03-1.53]; p=0.03) in women. Conclusions: Multiple biomarkers that signal the aging of biological organ systems can be combined to reflect BA. In our community-based sample, accelerated midlife BA was characterized by a higher risk of death and CVD in both sexes and with dementia risk in women. These findings underscore the importance of healthy multisystem aging over the life course.