Women are the neglected majority when it comes to cardiovascular health. Despite being the leading cause of death and disability in women (1), perception of the risk of cardiovascular disease, and its timely diagnosis and management tends to lag that in men. Women are less likely to receive guideline-recommended preventive therapy such as statins, despite good evidence that these are as effective as in men (2). Gender disparity extends to recent major trials which influence clinical practice. In an analysis of late breaking trials reported at major North American and European cardiology meetings, women were underrepresented, and less than half of the trials reported sex-specific data (3). In 2023, gender disparity that detrimentally impacts women’s cardiovascular health should not be an issue.
This scenario provided the impetus for a new call-to-action statement from the European Atherosclerosis Society (EAS) specifically authored by a female panel of cardiovascular experts. This statement identifies contributing factors that underpin this gender disparity. Beyond delayed diagnosis and undertreatment, sex-specific factors such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency) and polycystic ovary syndrome, adversely influence cardiometabolic risk factors (4, 5) and should be considered in cardiovascular risk assessment. Additionally, the modifiable risk factor profile of women may change during the life course. A key example is menopausal transition, which is associated with weight gain, visceral adiposity, and adverse effects on lipids, inflammatory biomarkers and blood pressure (6-8). Women are also subject to sociocultural influences, such as care responsibilities and mental health issues that may detrimentally impact their ability to seek healthcare when they need it (9-11).
A key focus of this EAS statement is on lipids and their management. The panel recognises that there is limited information on how female sex influences the major lipids integral to lipid panels in routine assessment. Despite this, there is evidence to indicate sex differences in lipid levels during early life (12, 13), as well as specific changes in lipid levels during the menstrual cycle(14), and life course events, notably pregnancy (15) and breast-feeding (16). The impact of these influences on the cholesterol burden of women with familial hypercholesterolaemia (FH) is highlighted. Not only are women with FH disadvantaged by delayed diagnosis and less than optimal treatment with statins and combination lipid lowering therapy (17), but pregnancy poses a particular challenge, due to the need to discontinue statins and other lipid lowering therapies (18). Although mandated on safety grounds, these recommendations contribute to an increase in the lifetime cholesterol burden of women with FH and potentially may exacerbate their risk of cardiovascular events compared with men with FH (19). A recent US Food and Drug Administration (FDA) statement allows for more flexible options for shared decision making in highest-risk women during pregnancy (20), although there is so far no response from the European Medicines Agency. For now, this EAS statement recommends close monitoring of FH women before, during and after pregnancy to limit their time-off statin therapy.
Beyond LDL-C, other lipids merit consideration. Elevated lipoprotein(a) [Lp(a)] is established as causal for cardiovascular disease in both men and women (21). However, as Lp(a) increases in women from the age of 50 years, coinciding with menopause transition, high Lp(a) is more prevalent among older women than older men, supported by data from the Copenhagen General Population Study (22). Therefore, a repeat Lp(a) measurement may be indicated in women after the menopause, which challenges the recommendation that Lp(a) should be measured only once during adulthood (18, 21). The statement also stresses the relevance of elevated plasma triglycerides, a marker for triglyceride-rich lipoproteins and their remnants (23), to cardiovascular risk in both women and men.
To address gaps in assessing risk and identifying and managing cardiovascular disease in women, this EAS statement makes several pragmatic recommendations, as well as highlighting the need for further study to understand how sex (hormones and chromosomes) influences atherosclerosis (Table 1). Strategic, targeted action involving all key stakeholders is a priority to overcome gender disparity in cardiovascular health in the 21st century.
Table 1. 2023 EAS statement recommendations on cardiovascular health in women
|· Cardiovascular health should be assessed routinely in women from a young age. Review should include traditional cardiovascular risk-enhancing factors, sex- specific cardiovascular risk factors, and gender-related cardiovascular risk factors.|
· Elevated lipids (LDL-C, triglycerides and lipoprotein(a)) should be treated early as recommended by guidelines.
· As high lipoprotein(a) levels are more common in women than men after 50 years, repeat measurement may be indicated.
· Women with FH should be closely followed to minimize time-off statin therapy due to pregnancy and breastfeeding. Whether treatment targets should be lowered in FH women to compensate for lost treatment time merits consideration.
· Women with non-obstructive coronary plaque should receive aggressive risk factor management.
· Further study is needed to understand how sex hormones and sex chromosomes influence the pathogenesis of atherosclerosis
Roeters van Lennep JE, Tokgözoğlu LS, Badimon L, Dumanski SM, Gulati M, Hess CN, Holven KB, Kavousi M, Kayıkçıoğlu M, Lutgens E, Michos ED, Prescott E, Stock JK, Tybjaerg-Hansen A, Wermer MJH, Benn M. Women, lipids and atherosclerotic cardiovascular disease: A call to action from the European Atherosclerosis Society. Eur Heart J 2023:DOI: https://doi.org/10.1093/eurheartj/ehad472
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