Cardiovascular Disease, Mortality Risk, and Healthcare Costs by Lipoprotein(a) Levels According to Low‐density Lipoprotein Cholesterol Levels in Older High‐risk Adults

Background The value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease ( CVD ) across low‐density lipoprotein cholesterol ( LDL ‐C) is uncertain. Hypothesis In older high‐risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs. Methods We included 3251 high‐risk subjects (prior CVD , diabetes, or 10‐year Framingham CVD risk >20%) age ≥65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD , coronary heart disease ( CHD ), and all‐cause mortality within LDL ‐C strata (spanning <70 mg/ dL to ≥160 mg/ dL ). We also examined 1‐year all‐cause and CVD healthcare costs from Medicare claims. Results Over a 22.5‐year follow‐up, higher Lp(a) levels predicted CVD and total mortality (both standardized hazard ratio [ HR ]: 1.06, P < 0.01), whereas higher LDL ‐C levels predicted higher CHD (standardized HR : 1.09, P < 0.01) but lower total mortality (standardized HR : 0.94, P < 0.001). Adjusted HRs in the highest (vs lowest) tertile of Lp(a) level were 1.95 ( P = 0.06) for CVD events and 2.68 ( P = 0.03) for CHD events when LDL ‐C was <70 mg/ dL . One‐year all‐cause healthcare costs were increased for Lp(a) ($771 per SD of 56 µg/ mL [ P = 0.03], $1976 for Lp(a) 25–64 µg/ mL vs <25 µg/ mL [ P = 0.02], and $1648 for Lp(a) ≥65 µg/ mL vs <25 µg/ mL [ P = 0.054]) but not LDL ‐C. Conclusions In older high‐risk adults, increased Lp(a) levels were associated with higher CVD risk, especially in those with LDL ‐C <70 mg/ dL , and with higher healthcare costs.