Abstract Body: Introduction: Single measures of cardiovascular health (CVH) have been related to risk of numerous outcomes beyond cardiovascular diseases (CVD). However, data are sparse regarding associations of cumulative CVH exposure across the life course with subclinical target organ damage (TOD) throughout the body.

Methods: We included Framingham Heart Study (FHS) Offspring participants who had data to calculate repeated Life’s Essential 8 (LE8) scores (range, 0-100; higher scores = better CVH) and were free of CVD at Exams 1-5 (1971-1995). Cumulative LE8 scores over time were estimated using a nonparametric cubic spline-based mixed effects model to compute the participant-specific cumulative area under the curve (AUC) of LE8 score from Exams 1-5, expressed as point-years (i.e., LE8 score of 60 points for 20 years ≈ 1200 point-years). Lower cumulative LE8 scores (e.g., lower point-years) indicate less favorable cumulative CVH exposure. Sixteen markers of cardiac, renal, pulmonary, and metabolic TOD were assessed at Exam 6 or later (1995-onwards). Nonlinear associations between cumulative LE8 scores and these 16 markers of subclinical TOD were examined using generalized additive models with a restricted cubic spline function, adjusted for age and maximal education, separately by sex.

Results: Among 2546 FHS participants, mean (SD) age at baseline was 35 (9) years, 1422 (56%) were female, and the mean (SD) cumulative LE8 score was 1215 (194) point-years over a 20-year period. In female participants (Figure), lower cumulative LE8 scores were associated with evidence of more adverse cardiac and vascular remodeling/injury (carotid intima-medial thickness, coronary artery calcium [CAC] score, high CAC burden, left ventricular mass index), renal dysfunction (urine albumin-creatinine ratio), worse pulmonary function (forced expiratory volume to forced vital capacity ratio, diffusion capacity), and metabolic dysfunction (hemoglobin A1c, total fat mass, subcutaneous adipose tissue). Cumulative LE8 scores were weakly associated with left ventricular ejection fraction, estimated glomerular filtration rate, high-sensitivity troponin I, and total lean mass. Similar patterns were observed among male participants.

Conclusion: Higher cumulative CVH across the life course was associated with lower cardiac, renal, pulmonary, and metabolic TOD. Public health strategies are needed to promote and maintain high LE8 scores at all ages to prevent TOD and progression to clinical events.