Abstract Body: Overview:
Lipoprotein(a) (Lp(a)) is a risk factor for atherosclerotic coronary artery disease (CAD). Little is known about menopausal status and hormone therapy in racial/ethnic-specific associations of elevated Lp(a) with CAD. We investigated this in an age- and racially-diverse cohort of women from the U.S.’s largest integrated healthcare system.
Methods:
We extracted structured cross-sectional electronic health record data for 2831 women with a laboratory result for Lp(a) between 1999-2023 in the Veterans Health Administration. We designated menopausal status (pre, surgical, natural), use of hormone contraception or menopausal hormone therapy (HT), and history of CAD as of the Lp(a) test date. Elevated Lp(a) was Lp(a) >125 nmol/L. Using multivariate logistic regression with correction for multiple comparisons, we estimated association of elevated Lp(a) with prevalent CAD adjusted for age, race/ethnicity, menopausal status, and HT. Within menopausal subgroups, we conducted analogous multivariate logistic regressions. We tested for interaction between Lp(a) and menopausal status and between HT and race/ethnicity.
Results:
Elevated Lp(a) was associated with prevalent CAD among all women (OR=1.5, 95% CI [1.2, 1.9], p<0.002). In subgroup analysis by menopause status, elevated Lp(a) was associated with prevalent CAD only for women over 60 with natural menopause (OR=2.1, 95% CI [1.5, 3.0], p<0.001). An interaction model between elevated Lp(a) and menopause status on prevalent CAD was assessed with premenopausal women under 60 without elevated Lp(a) as the reference group. Premenopausal women under 60 with elevated Lp(a) had an OR of 1.4 (95% CI [0.8, 2.5] p=0.274). Women over 60 with natural menopause and without elevated Lp(a) had an OR of 4.9 (95% CI [3.4, 7.3], p<0.001). Women over 60 with natural menopause and elevated Lp(a) had the highest OR of 10.4 (95% CI [6.7, 16.0], p<0.001). Relative excess risk due to interaction (RERI) of 5.1 (95% CI [2.2, 9.7]) supports an additive interaction of menopausal status over/under age 60 with Lp(a) on risk of prevalent CAD. The p-value for multiplicative interaction was 0.22.
In smaller-sized menopausal subgroups, no observations were observed between race/ethnicity and HT on risk of elevated Lp(a) or on prevalent CAD.
Conclusions:
Menopausal status over age 60 and elevated Lp(a) (>125 nmol/L) interacted to modify the risk of prevalent CAD. HT use as a possible effect modifier, by race/ethnicity, warrants further exploration.