Age at Menopause, Leukocyte Telomere Length, and Coronary Artery Disease in Postmenopausal Women
Art Schuermans et al (Circ Res. 2023 Aug 18;133(5):376-386.
doi: 10.1161/CIRCRESAHA.123.322984. Epub 2023 Jul 25.
DOI: 10.1161/CIRCRESAHA.123.322984) investigated the role of leukocyte telomere length (LTL), a marker of cellular aging and genomic instability, in the association of premature menopause with cardiovascular disease, since premature menopause is a risk factor for accelerated cardiovascular aging.
The study included 130 254 postmenopausal women (UK Biobank: n=122 224; Women’s Health Initiative: n=8030), of whom 4809 (3.7%) had experienced menopause before age 40. Earlier menopause was associated with shorter LTL (meta-analyzed ß=-0.02 SD/5 years of earlier menopause [95% CI, -0.02 to -0.01]; P=7.2×10-12). This association was stronger and significant in both cohorts for women with natural/spontaneous menopause (meta-analyzed ß=-0.04 SD/5 years of earlier menopause [95% CI, -0.04 to -0.03]; P<2.2×10-16) and was independent of hormone therapy use. Mendelian randomization supported a causal association of shorter genetically predicted LTL with earlier age at natural menopause. LTL and age at menopause were independently associated with incident coronary artery disease, and mediation analyses indicated small but significant mediation effects of LTL in the association of menopausal age with coronary artery disease.
The authors concluded that earlier age at menopause is associated with shorter LTL, especially among women with natural menopause, and that this may may contribute to the heightened cardiovascular risk associated with premature menopause.