Causal role of reproductive factors on women’s CVD health identified
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Key takeaways :
- Increased odds for coronary artery disease, heart failure and stroke were seen with earlier genetically predicted age at first birth.
- Close monitoring and early intervention can mitigate women’s CV risks.
Results of a Mendelian randomization study support a causal role of several reproductive factors on women’s risks for cardiovascular disease, according to researchers.
Results were published in the Journal of the American Heart Association.
“Because the process of random allele assortment at conception leads to an effective ‘randomization’ of individuals to high or low genetic risk of diseases or phenotypes, the genetic liability for a risk factor (eg, age at menarche) can be used as a proxy indicator for the exposure,” researchers wrote in study background. “Because the allocation to ‘high’ or ‘low’ genetic risk is random and therefore not influenced by confounding or reverse causation, this framework can be used to infer causality of the risk factor on an outcome under a set of key assumptions.”
Ardissino, Ng and colleagues extracted uncorrelated, genome-wide significant single nucleotide polymorphisms from sex-specific genome-wide association studies of age at first birth, number of live births, age at menarche and age at menopause. Using inverse-variance weighted Mendelian randomization, the researchers evaluated outcomes of atrial fibrillation, coronary artery disease, heart failure, ischemic stroke and stroke.
Researchers observed increased odds for coronary artery disease (OR = 1.49; 95% CI, 1.28-1.74), heart failure (OR = 1.27; 95% CI, 1.06-1.53) and stroke (OR = 1.25; 95% CI, 1-1.56) among women with earlier genetically predicted age at first birth. Odds were partially mediated through BMI, type 2 diabetes, blood pressure and cholesterol traits, according to the researchers.
In addition, researchers noted increased odds for atrial fibrillation (OR = 2.91; 95% CI, 1.16-7.29), heart failure (OR = 1.9; 95% CI, 1.28-2.82), ischemic stroke (OR = 1.86; 95% CI, 1.03-3.37) and stroke (OR = 2.07; 95% CI, 1.22-3.52) with a higher genetically predicted number of live births. Earlier genetically predicted age at menarche also was associated with an increased risk for coronary artery disease (OR = 1.1; 95% CI, 1.06-1.14) and heart failure (OR = 1.12; 95% CI, 1.07-1.17) with both associations partly mediated by BMI.
“From a clinical perspective, the results stress the importance of routine evaluation of sex-specific factors in clinical risk stratification. In women who have these risk factors, our results highlight the importance of early modification of cardiometabolic factors, as this will at least partly mitigate the increased cardiovascular risk conferred by these reproductive factors,” researchers Maddalena Ardissino, MBBS, BSc, MSc, MRCP, honorary clinical research fellow at the National Heart and Lung Institute at Imperial College London and the Nuffield department of population health at the University of Oxford, U.K., and Fu Siong Ng, MBBS, PhD, clinical senior lecturer in cardiac electrophysiology at the National Heart and Lung Institute at Imperial College London, London, U.K., told Healio.
According to Ardissino and Ng, the lack of association between age at menopause and CVD was surprising, but they suggested two potential explanations: The study may not have had sufficient power to detect an association or previous observational associations might be due to residual confounding.
“Our study highlights the importance of evaluating sex-specific factors to better understand the components of cardiovascular disease risk in women that are currently not fully explained by the ‘traditional’ risk factors,” Ardissino and Ng said. “By highlighting these associations and their causal nature, we encourage more research exploring the causal relevance of more sex-specific factors, including those related to obstetric history, with cardiovascular disease. It will also be important to establish the mechanistic pathways that underpin the overlap between obstetric and gynecological history with cardiovascular disease in order to be able to better target primary prevention.”
For more information:
Maddalena Ardissino, MBBS, BSc, MSc, MRCP, can be reached at maddalena.ardissino13@imperial.ac.uk.
Fu Siong Ng, MBBS, PhD, can be reached at f.ng@imperial.ac.uk.