EAS issues ‘call-to-action’ statement on women, lipids, and atherosclerotic cardiovascular disease

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


1.           Timmis A, Vardas P, Townsend N, Torbica A, Katus H, De Smedt D, et al. European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J. 2022;43(8):716-99.

2.           Cholesterol Treatment Trialists C, Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397-405.

3.           Holtzman JN, Kaur G, Power JE, Barkhordarian M, Mares A, Goyal A, et al. Underrepresentation of women in late-breaking cardiovascular clinical trials. J Womens Health (Larchmt). 2023;32(6):635-40.

4.           Elder P, Sharma G, Gulati M, Michos ED. Identification of female-specific risk enhancers throughout the lifespan of women to improve cardiovascular disease prevention. Am J Prev Cardiol. 2020;2:100028.

5.           Agarwala A, Michos ED, Samad Z, Ballantyne CM, Virani SS. The use of sex-specific factors in the assessment of women’s cardiovascular risk. Circulation. 2020;141(7):592-9.

6.           Matthews KA, Crawford SL, Chae CU, Everson-Rose SA, Sowers MF, Sternfeld B, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol. 2009;54(25):2366-73.

7.           Lau ES, Michos ED. Blood pressure trajectories through the menopause transition: different paths, same journey. Circ Res. 2022;130(3):323-5.

8.           El Khoudary SR, Aggarwal B, Beckie TM, Hodis HN, Johnson AE, Langer RD, et al. Menopause transition and cardiovascular disease risk: implications for timing of early prevention: A Scientific Statement From the American Heart Association. Circulation. 2020;142(25):e506-e32.

9.           Colella TJF, Hardy M, Hart D, Price JAD, Sarfi H, Mullen KA, et al. The Canadian Women’s Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women-Chapter 3: Patient Perspectives. CJC Open. 2021;3(3):229-35.

10.        Connelly PJ, Azizi Z, Alipour P, Delles C, Pilote L, Raparelli V. The importance of gender to understand sex differences in cardiovascular disease. Can J Cardiol. 2021;37(5):699-710.

11.        Norris CM, Yip CYY, Nerenberg KA, Clavel MA, Pacheco C, Foulds HJA, et al. State of the Science in Women’s Cardiovascular Disease: A Canadian Perspective on the Influence of Sex and Gender. J Am Heart Assoc. 2020;9(4):e015634.

12.        Oyri LKL, Bogsrud MP, Christensen JJ, Ulven SM, Brantsaeter AL, Retterstol K, et al. Novel associations between parental and newborn cord blood metabolic profiles in the Norwegian Mother, Father and Child Cohort Study. BMC Med. 2021;19(1):91.

13.        Balder JW, Lansberg PJ, Hof MH, Wiegman A, Hutten BA, Kuivenhoven JA. Pediatric lipid reference values in the general population: The Dutch lifelines cohort study. J Clin Lipidol. 2018;12(5):1208-16.

14.        Mumford SL, Dasharathy S, Pollack AZ, Schisterman EF. Variations in lipid levels according to menstrual cycle phase: clinical implications. Clin Lipidol. 2011;6(2):225-34.

15.        Klajnbard A, Szecsi PB, Colov NP, Andersen MR, Jorgensen M, Bjorngaard B, et al. Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Clin Chem Lab Med. 2010;48(2):237-48.

16.        Zhang Z, Lai M, Piro AL, Alexeeff SE, Allalou A, Rost HL, et al. Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: the SWIFT study. BMC Med. 2021;19(1):241.

17.        Collaboration EASFHS. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet. 2021;398(10312):1713-25.

18.        Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-88.

19.        Johansen AK, Bogsrud MP, Christensen JJ, Rundblad A, Narverud I, Ulven S, et al. Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up. Atheroscler Plus. 2023;51:28-34.

20.        US Food And Drugs Administration. Drug Safety Communication 7-20-2021. FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. 2021 [Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy#:~:text=Statins%20are%20safe%20to%20prescribe%20in%20patients%20who%20are%20not,not%20generally%20necessary%20during%20pregnancy.

21.        Kronenberg F MS, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, Dweck MR, Koschinsky M,  Lambert G, Mach F, McNeal CJ, Moriarty PM, Natarajan P, Nordestgaard BG, Parhofer KG, Virani SS, von Eckardstein A, Watts GF, Stock JK, Ray RR, Tokgözoğlu LS, Catapano AL.  . Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. . Eur Heart J. 2022.

22.        Simony SB, Mortensen MB, Langsted A, Afzal S, Kamstrup PR, Nordestgaard BG. Sex differences of lipoprotein(a) levels and associated risk of morbidity and mortality by age: The Copenhagen General Population Study. Atherosclerosis. 2022;355:76-82.

23.        Ginsberg HN, Packard CJ, Chapman MJ, Boren J, Aguilar-Salinas CA, Averna M, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021;42(47):4791-806.