Early Midlife Cardiovascular Health Influences Future HDL Metrics in Women: The SWAN HDL Study

BACKGROUND: Utility of high‐density lipoprotein cholesterol (HDL‐C) in assessing the antiatherogenic properties of HDL may be limited in midlife women. Novel metrics of HDL function, lipid contents, and subclasses may better reflect the atheroprotective capacities of HDL, supporting the need to evaluate how cardiovascular health affects these metrics in women. We assessed the relationship of early midlife Life's Simple 7 (LS7) score and its health behavior components with future HDL function (HDL–cholesterol efflux capacity), HDL‐phospholipid, HDL‐triglyceride, HDL particles (HDL‐P) and size, and the relationship between LS7 score and changes in HDL metrics over time. METHODS AND RESULTS: We analyzed 529 women (baseline age: 46.4 [2.6] years, 57% White) from the SWAN HDL (Study of Women's Health Across the Nation HDL) study who had baseline LS7 followed by future repeated HDL metrics. Multivariable linear mixed models were used. Higher LS7 score was associated with favorable future HDL profile (higher HDL‐phospholipid, total HDL‐P and large HDL‐P, lower HDL‐triglyceride, and larger overall HDL size). Ideal body mass index was associated with higher HDL–cholesterol efflux capacity, HDL‐phospholipid, and large HDL‐P, lower HDL‐triglyceride and small HDL‐P, and larger overall HDL size. Ideal physical activity was associated with higher HDL‐phospholipid, and total, large, and medium HDL‐P. Ideal smoking was associated with less HDL‐triglycerides. Diet was not related to HDL metrics. Higher LS7 score and ideal body mass index were associated with slower progression of HDL size over time. CONCLUSIONS: Novel HDL metrics may better reflect the clinical utility of HDL. Improving lifestyle at midlife, particularly maintaining ideal body mass index, is associated with better future HDL phenotype.