Reproductive factors in women associated with increased CV risk

By Rebecca Jenkins

Having a higher number of children and going through menarche at an earlier age are among the female-specific risk factors linked to increased cardiovascular disease (CVD), genetic analysis shows.

Researchers used Mendelian randomisation on genetic data from more than 100,000 women to examine the link between the genes that predict certain female reproductive factors and CVD risk.

A higher genetically predicted number of live births increased risk of atrial fibrillation, heart failure, ischaemic stroke and stroke, they reported in the Journal of the American Heart Association.

Earlier genetically predicted age at first birth increased coronary artery disease, heart failure and stroke, with partial mediation through BMI, type 2 diabetes, blood pressure and cholesterol traits. Earlier genetically predicted age at menarche increased risk of coronary artery disease and heart failure, with BMI at least partly mediating both associations. However, there was no association between age of menopause and risk of CVD.

‘These results support a causal role of a number of reproductive factors on [CVD] in women and identify multiple modifiable mediators amenable to clinical intervention,’ the study authors concluded.

Associate Professor Clare Arnott, Director of the Cardiovascular, and Global Chronic and Complex Diseases Programs at the George Institute for Global Health in Sydney, welcomed the research saying previous observational studies had shown sex-specific risk factors were connected to CVD in women, but it had been less clear whether these factors were causal.

‘This study uses Mendelian randomisation as a really eloquent and clever way of trying to assess causation,’ she told Medicine Today.

Professor Arnott noted traditional cardiometabolic risk factors such as BMI explained some, but not all, of the link between some sex-specific risk factors, giving clinicians and women modifiable targets to address.

‘However, it does not mean we should dismiss the importance of the sex-specific factors, such as age of menarche and obstetric history. Whilst they may not be modifiable, they identify women at risk, often at a pivotal time-point in their lives, such as pregnancy, and  in whom education, close follow up and intensive lifestyle modification are almost certainly of benefit to their long-term cardiometabolic health  and overall health trajectory,’ she said.

New CV algorithms which included sex-specific factors were also essential, with traditional CV risk prediction models known to perform poorly in women, particularly across non-Caucasian populations.

‘We need large datasets that possess both traditional and sex-specific risk factors in large, diverse, representative populations that are followed up for many years with all cardiovascular events recorded. Those data exist but need to be harnessed to develop new algorithms,’ Professor Arnott said.

JAHA 2023; 12: e027933.