Women may need stronger treatment than men to prevent heart attacks

Women with clogged arteries are at higher risk of heart attacks and may need stronger treatment postmenopause than men of similar age.

The results of a study in nearly 25,000 adults presented at a scientific congress of the European Society of Cardiology – EACVI 2023 – in Barcelona and also published in European Heart Journal – Cardiovascular Imaging, suggest postmenopausal women could need higher levels of cholesterol busting drugs to help reduce the risk of cardiovascular disease.

This is because women’s coronary arteries are slightly narrower than men’s, so the same amount of arterial plaque that occurs when cholesterol builds up in the inner lining, would have a more significant impact on blood flow.

Falling oestrogen levels could also make postmenopausal women more susceptible to heart disease. The hormone naturally produced by women during their reproductive years is known to help keep blood vessels healthy, preventing atherosclerosis, or narrowing, caused by fat and cholesterol deposits, and lowering the incidence of cardiovascular disease.

While young women do have heart attacks, usually they develop atherosclerosis later in life than men and have cardiac arrests at an older age than males.

Study author Dr Sophie van Rosendael of Leiden University Medical Centre in the Netherlands, said: “The study suggests that a given burden of atherosclerosis is riskier in postmenopausal women than it is in men of that age.

“Since atherosclerotic plaque burden is emerging as a target to decide the intensity of therapy to prevent heart attacks, the findings may impact treatment. Our results indicate that after menopause, women may need a higher dose of statins or the addition of another lipid-lowering drug.”

But more research is needed to confirm these findings, she added.

This study examined whether the prognostic importance of atherosclerotic plaques are the same for women and men at different ages, as this could be important for selecting treatments to prevent heart attacks.

The research included 11,678 women with an average age of 58.5 years and 13,272 men with a mean age of 55.6, who were referred for coronary computed tomography angiography (CCTA) to obtain 3D images of the arteries in the heart, and then enrolled in the CONFIRM registry – a large observational study conducted in six countries in North America, Europe, and Asia.

Total atherosclerotic burden was rated using the Leiden CCTA score, which incorporates the following items for each coronary segment: plaque presence (yes/no), composition (calcified, noncalcified or mixed), location, and severity of narrowing, for a final value of 0 to 42.

Patients were divided into three categories previously found to predict the risk of suffering a heart attack: low atherosclerotic burden (0 to 5), medium (6 to 20) and high (over 20).

In addition, obstructive coronary artery disease was defined as 50% narrowing or more.

The primary outcome was the difference in Leiden CCTA score between women and men of similar age.

The investigators also analysed sex differences in the rates of major adverse cardiovascular events (MACE), which included all-cause death and heart attacks, after adjusting for age and cardiovascular risk factors, including hypertension, high cholesterol, diabetes, current smoking and family history of coronary artery disease.

The study showed an approximately 12 year delay in the onset of coronary atherosclerosis in women: the median Leiden CCTA risk score was above zero at age 64 to 68 years in women versus 52 to 56 years in men.

In addition, the overall plaque burden as quantified by the Leiden CCTA score was significantly lower in women, who had more non-obstructive disease.

Dr van Rosendael explained: “The results confirm the previously reported delay in the start of atherosclerosis in women. We also found that women are more likely to have non-obstructive disease. It was formerly thought that only obstructive atherosclerosis caused myocardial infarction but we now know that non-obstructive disease is also risky.”

The burden of atherosclerosis was equally predictive of MACE in premenopausal women (under 55-years-old) and men of the same age group. However, in postmenopausal women (55 years and older), the risk of MACE was higher than men for a given score.

In postmenopausal women, compared to those with a low burden, those with a medium and high burden had 2.21-fold and 6.11-fold higher risks of MACE. While in men aged 55 years and older, compared to those with a low burden, those with a medium and high burden had 1.57-fold and 2.25-fold greater risks of MACE.

Dr van Rosendael said: “In this study, the elevated risk for women versus men was especially observed in postmenopausal women with the highest Leiden CCTA score.

“This could be partly because the inner diameter of coronary arteries is smaller in women, meaning that the same amount of plaque could have a larger impact on blood flow.

“Our findings link the known acceleration of atherosclerosis development after menopause with a significant increase in relative risk for women compared to men, despite a similar burden of atherosclerotic disease. This may have implications for the intensity of medical treatment.”

Heart attacks are often seen as a primarily male health concern, but cardiovascular disease is actually the leading cause of death for women globally.  According to the World Health Organisation, the top four leading causes of death for women are ischemic heart disease, stroke, lower respiratory infections and chronic obstructive pulmonary disease.

Breast cancer – believed by many to be the most common cause of death – is number eight on the list.

A report published in May 2021 by the Lancet Commission on women and cardiovascular disease found females remain “understudied, under-recognised, underdiagnosed and undertreated.”

This, the report stated, is despite decades of grassroots campaigns which have helped to raise awareness about the impact of cardiovascular disease in women, and the positive changes affecting women and their health which have gained momentum.