Early age at menarche linked to carotid intima-media thickness
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Key takeaways:
- Early age at menarche was linked to greater thickness of the carotid artery intima-media, an early sign of atherosclerosis.
- Early intervention to control BMI and blood pressure may lower ASCVD risk.
Genetically predicted early age at menarche was associated with increased carotid intima-media thickness, an early marker of subclinical atherosclerosis and medial hypertrophy, researchers reported.
It was estimated that one-third of the effect of age at menarche on carotid intima-media thickness could be moderated by BMI and systolic BP, according to data published in the Journal of the American Heart Association.
“Emerging evidence suggests that sex-specific risk factors such as age at menarche (AAM), age at menopause, and timing and number of births also contribute to a woman’s unique CVD risk, in addition to the traditionally established CVD risk factors,” Devendra Meena, DPhil, of the department of epidemiology and biostatistics in the School of Public Health at Imperial College London, and colleagues wrote. “Earlier AAM has also been associated with other traditional cardiometabolic risk factors, including higher BMI, higher blood pressure, and abnormal glycemia in adolescents. ... A better understanding of the relationship between pubertal timing, modifiable cardiometabolic risk factors and subclinical atherosclerosis may contribute to early intervention and improved disease management.”
To evaluate the association between age at menarche and carotid intima-media thickness, Meena and colleagues conducted a genome-wide association study using data from more than 300,000 women of European ancestry from the ReproGen consortium, 23andMe and UK Biobank.
After causality between age at menarche and carotid intima-media thickness was assessed, cardiometabolic moderators of this association were also evaluated.
Using genetic variants that passed Steiger filtering, Meena and colleagues observed that genetically predicted earlier age at menarche was associated with higher carotid intima-media thickness (P inverse-variance weighted = .002).
After cross-trait linkage disequilibrium score regression and Mendelian randomization, an inverse correlation between age at menarche and BMI, systolic BP and triglycerides (P for all < .001) was reported, as well as a positive genetic correlation between age at menarche and HDL (P < .001).
Meena and colleagues estimated that 20.1% of the effect of genetically predicted age at menarche on carotid intima-media thickness was mediated by BMI (95% CI, 1.4-38.9) and 13.5% was mediated by systolic BP (95% CI, 0.5-26.6).
“This Mendelian randomization study provides evidence that genetically predicted earlier age at menarche is potentially causally associated with carotid intima-media thickness, a marker of subclinical atherosclerosis,” the researchers wrote. “Early intervention aimed at lowering body mass index and hypertension may be beneficial in reducing the risk of developing subclinical atherosclerosis due to earlier age at menarche.”
The researchers noted that due to their genome-wide association study only including women of European ancestry, the results may not be applicable to other populations and ethnicities due to allelic differences.
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