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Dr Wendy Hall – Women’s health: a lifelong pursuit of the heart

 

More than 3.5 million women in the UK are living with heart disease1. However, it is often perceived as a “man’s disease”. Historically, these misperceptions have meant that women are often overlooked when assessing risk of cardiovascular disease (CVD), and there are many reports of women experiencing delays in diagnosis and subsequently receiving poorer treatment compared to men 2,3. For example, diabetes diagnosis tends to occur at an older age in women, as well as at a greater degree of overweight, and often at a more advanced stage of the disease4. With diabetes having a greater impact on increased risk of incident coronary heart disease (CHD) in women relative to men5,6, earlier diagnosis of diabetes is a top priority as a key strategy in female CVD prevention.

Similarly, although the approach to treating high cholesterol and triglycerides is the same for men and women, research shows that women are less likely to be prescribed cholesterol-lowering drugs compared to men at all ages up to 757. Inequalities in healthcare delivery are demonstrated by poorer survival chances for women who go on to suffer a heart attack8. The statistics are alarming: worldwide, CHD is the single biggest cause of death in both men and women, and in the UK it kills more than twice as many women as breast cancer across all age groups9,10. It is essential that we continue to make heart health a priority for women of all ages11.

Many of the modifiable risk factors for CVD are common to both men and women. These include:

  • obesity
  • hypertension
  • diabetes
  • dyslipidaemia

As well as lifestyle-related factors such as:

  • poor diet
  • lack of physical activity
  • smoking
  • excess alcohol consumption

However, the weighting of risk can differ between sexes. For example, having a higher systolic blood pressure, being a smoker, and having diabetes are all associated with a greater risk of myocardial infarction for women compared with men12.

Many under-recognised risk factors disproportionately affect women, such as:

  • socioeconomic status
  • exposure to deprivation
  • job-related stress
  • psychosocial stress
  • depression
  • being affected by abuse/violence2

Whilst men tend to develop CVD approximately 10 years earlier than women, menopause brings an acceleration in risk, driven by a sharp increase in LDL cholesterol, central fat deposition, endothelial dysfunction, and blood pressure13. Reduced secretion of oestrogen is thought to be primarily responsible. Oestrogen receptors are widely distributed in the cardiovascular system; oestrogen may protect women by improving vascular function and repair, reducing oxidative stress, improving mitochondrial function and reducing fibrosis. However, dietary habits, work and home-related stress, and reduced physical activity are also implicated in the rapid deterioration in cardiovascular health during this period in women’s lives14.

There are a number of female-specific risk factors that are not included in risk estimate algorithms such as QRISK-3. In fact, a study of more than 120,000 patients found that up to 15% of women under the age of 65 with CHD did not have hypertension, hyperlipidaemia, diabetes, or smoke15. Gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, and pre-term delivery may persist in their effects on the cardiovascular system beyond pregnancy, leading to increased risk of CVD16. Exposure in young adulthood to reproductive endocrine/gynaecological disorders such as polycystic ovary syndrome, endometriosis or premature menopause are associated with risk factors for CVD13. Finally, other aspects of reproductive life history may be relevant for CVD risk in women, such as early age of menarche17 and duration/type of oral contraception18.

As part of the NHS Long Term plan, the 5-yearly NHS Health Check for men and women aged 40-74 is designed to monitor CVD risk factors and offer advice on diet, exercise, smoking and weight management, and may result in pharmacological treatment for hypertension or hyperlipidemia.

The Public Health England Best Practice Guideline for NHS Health Check recommends considering additional risk in women with past gestational diabetes or with polycystic ovary syndrome in addition to the generic risk filter for the assessment of diabetes risk19. Otherwise, this fairly generic approach to CVD prevention is at least partly attributable to the fact that women, especially women from national minority ethnic groups, have been under-represented as participants in clinical trials for CHD and heart failure and as a result, there is a dire lack of evidence to inform the development of female-focused risk estimates11.

Over the past decade there has been a concerted effort to implement change20, but considering large and longitudinal studies are resource-intensive and it can take a long time to reach an evidence-based consensus, a targeted approach may take some time to achieve.

So what can be done to rectify the current inequities in preventative treatment and cardiac rehabilitation experienced by women across the world?

Atherosclerosis begins in childhood21, so approaching CVD prevention as a lifelong undertaking is crucial to any strategy. Behaviour change strategies need to be tailored to pre-, peri- and post-menopausal women as they experience different barriers at various life stages22,23.

Younger women attending routine healthcare appointments should be checked for CVD risk factors and sign-posted to sources of behaviour change support; this is particularly crucial where there are sex-specific risk factors present such as polycystic ovary syndrome, premature menopause or endometriosis. An estimated 10-15% of women experience an adverse pregnancy outcome and consequently have a twofold increased risk of CVD after gestational diabetes 24, pre-eclampsia25 or gestational hypertension26. Regular and sustained monitoring and management of CVD risk factors should be continued beyond pregnancy.

Although there are currently no risk stratification algorithms that incorporate sex-specific risk factors to aid decision making on pharmacotherapy, this is mainly due to lack of data in younger women, whereas older women may have already developed traditional risk factors such as hypertension and type 2 diabetes. Women who seek healthcare advice during peri- and post-menopause should be assessed for CVD risk, including measuring waist circumference (which may be a more important indicator of risk than BMI, especially as oestrogen levels decline), and it is important that their past history of pregnancy and reproductive disorders should be taken into account when deciding on risk management strategies and treatment.

The importance of lifelong healthy eating, being physically active, and maintaining a healthy body weight for reducing preventable cardiovascular deaths cannot be overstated; these three factors along with non-smoking could have prevented ~70% of incident CHD events in women with an average age of 50 after 20 years of follow up27.

When it comes to heart-healthy dietary advice, particular emphasis should be put on:

  • consuming a diet rich in wholegrains, fruits and vegetables, nuts and seeds and other plant-based protein sources such as soy, beans and pulses
  • using spreads and oils rich in unsaturated fats
  • limiting alcohol intake & sugar-sweetened beverages
  • limiting salt, red and processed meat, and bakery and dessert products rich in saturated fats and refined starches and sugars28
  • Pre-menopausal women should be encouraged to eat 2 portions of fish per week, at least one of which should be oily, as evidence supports the cardioprotective effects of regular fish consumption29
  • Girls and women of childbearing age are advised not to consume more than 2 portions of oily fish per week, but postmenopausal women can eat up to 4 portions of oily fish per week.

In addition to these dietary changes, women with raised blood LDL cholesterol, even if taking statins, can significantly lower their blood cholesterol by consuming 2-3 g per day of plant sterols or plant stanols in fortified foods such as spreads30.

Increasingly research is showing how important physical activity is for prevention of CVD in older women. Reducing sedentary time by an hour a day was associated with 26% lower risk of heart disease in women with an average age of 7931, and activities such as gardening or walking should be strongly encouraged32.

Finally, the significant benefit of adequate sleep duration in women mid-life is another opportunity for lifestyle modification in short-sleepers that could reduce CVD risk by 10% 33.

Women have different risk profiles, barriers to diagnosis and treatment, as well as differing pathophysiology of CVD, and many cardiovascular deaths and incidences could be prevented by utilising growing datasets on these female-specific factors to refine clinical guidelines.

**

Dr Wendy Hall took up her first academic appointment at King’s College London in 2005. In 2016, Dr Hall received the Nutrition Society’s Silver Medal for her contribution to nutritional science, and in 2018 she was appointed to the role of the Nutrition Society’s Theme Leader for Whole Body Metabolism and more recently for Nutrition and Optimum Life Course. She leads a diet and cardiometabolic health research group within the Department of Nutritional Sciences and is the departmental postgraduate research co-ordinator. She received the Faculty of Life Sciences & Medicine Supervisory Excellence Award in 2018.

**

References

1. British Heart Foundation. Twice as deadly as breast cancer. Heart Matters magazine. https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/women/coronary-heart-disease-kills. Accessed June 10, 2021.

2. Vogel B, Acevedo M, Appelman Y, et al. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet. May 2021. doi:10.1016/S0140-6736(21)00684-X

3. Vynckier P, Ferrannini G, Rydén L, et al. Gender gap in risk factor control of coronary patients far from closing: results from the European Society of Cardiology EUROASPIRE V registry. Eur J Prev Cardiol. December 2020. doi:10.1093/eurjpc/zwaa144

4. Appelman Y, van Rijn BB, Ten Haaf ME, Boersma E, Peters SAE. Sex differences in cardiovascular risk factors and disease prevention. Atherosclerosis. 2015;241(1):211-218. doi:10.1016/j.atherosclerosis.2015.01.027

5. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332(7533):73-78. doi:10.1136/bmj.38678.389583.7C

6. de Jong M, Woodward M, Peters SAE. Diabetes, Glycated Hemoglobin, and the Risk of Myocardial Infarction in Women and Men: A Prospective Cohort Study of the UK Biobank. Diabetes Care. 2020;43(9):2050 LP – 2059. doi:10.2337/dc19-2363

7. O’Keeffe AG, Petersen I, Nazareth I. Initiation rates of statin therapy for the primary prevention of cardiovascular disease: an assessment of differences between countries of the UK and between regions within England. BMJ Open. 2015;5(3):e007207-e007207. doi:10.1136/bmjopen-2014-007207

8. Wilkinson C, Bebb O, Dondo TB, et al. Sex differences in quality indicator attainment for myocardial infarction: a nationwide cohort study. Heart. 2019;105(7):516-523. doi:10.1136/heartjnl-2018-313959

9. World Health Organization. The top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed June 10, 2021.

10. World Health Organization. The Global Health Observatory. https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death. Accessed June 10, 2021.

11. McSweeney JC, Rosenfeld AG, Abel WM, et al. Preventing and Experiencing Ischemic Heart Disease as a Woman: State of the Science. Circulation. 2016;133(13):1302-1331. doi:10.1161/CIR.0000000000000381

12. Millett ERC, Peters SAE, Woodward M. Sex differences in risk factors for myocardial infarction: cohort study of UK Biobank participants. BMJ. November 2018:k4247. doi:10.1136/bmj.k4247

13. Maas AHEM, Rosano G, Cifkova R, et al. Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists. Eur Heart J. 2021;42(10):967-984. doi:10.1093/eurheartj/ehaa1044

14. Li Y, Zhao D, Wang M, et al. Combined effect of menopause and cardiovascular risk factors on death and cardiovascular disease: a cohort study. BMC Cardiovasc Disord. 2021;21(1):109. doi:10.1186/s12872-021-01919-5

15. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898-904. doi:10.1001/jama.290.7.898

16. Parikh NI, Gonzalez JM, Anderson CAM, et al. Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women: A Scientific Statement From the American Heart Association. Circulation. 2021;143(18):e902-e916. doi:10.1161/CIR.0000000000000961

17. Lakshman R, Forouhi NG, Sharp SJ, et al. Early Age at Menarche Associated with Cardiovascular Disease and Mortality. J Clin Endocrinol Metab. 2009;94(12):4953-4960. doi:10.1210/jc.2009-1789

18. Harvey RE, Coffman KE, Miller VM. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health (Lond Engl). 2015;11(2):239-257. doi:10.2217/whe.14.64

19. Public Health England. NHS Health Check. Best Practice Guidance.; 2016.

20. American Heart Association. Research Goes Red. https://www.goredforwomen.org/en/get-involved/research-goes-red#:~:text=Research Goes Red aims to,prevent heart disease in women. Accessed June 10, 2021.

21. McGill HC, McMahan CA. Determinants of atherosclerosis in the young. Am J Cardiol. 1998;82(10):30-36. doi:10.1016/S0002-9149(98)00720-6

22. Pegington M, French DP, Harvie MN. Why young women gain weight: A narrative review of influencing factors and possible solutions. Obes Rev. 2020;21(5). doi:10.1111/obr.13002

23. World Health Organization. Women, Ageing and Health : A Framework for Action : Focus on Gender.; 2007.

24. Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia. 2019;62(6):905-914. doi:10.1007/s00125-019-4840-2

25. Benschop L, Duvekot JJ, Roeters van Lennep JE. Future risk of cardiovascular disease risk factors and events in women after a hypertensive disorder of pregnancy. Heart. 2019;105(16):1273-1278. doi:10.1136/heartjnl-2018-313453

26. Riise HKR, Sulo G, Tell GS, et al. Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women. J Am Heart Assoc. 2018;7(10). doi:10.1161/JAHA.117.008337

27. Chomistek AK, Chiuve SE, Eliassen AH, Mukamal KJ, Willett WC, Rimm EB. Healthy Lifestyle in the Primordial Prevention of Cardiovascular Disease Among Young Women. J Am Coll Cardiol. 2015;65(1):43-51. doi:10.1016/j.jacc.2014.10.024

28. Choices N. The Eatwell Guide – Live Well – NHS Choices. Uk. 2016.

29. Public Health England. The Scientific Advisory Committee on Nutrition and Committee on Toxicity Advice on Benefits and Risks Related to Fish Consumption.; 2004.

30. Gylling H, Radhakrishnan R, Miettinen TA. Reduction of Serum Cholesterol in Postmenopausal Women With Previous Myocardial Infarction and Cholesterol Malabsorption Induced by Dietary Sitostanol Ester Margarine. Circulation. 1997;96(12):4226-4231. doi:10.1161/01.CIR.96.12.4226

31. Bellettiere J, LaMonte MJ, Evenson KR, et al. Sedentary Behavior and Cardiovascular Disease in Older Women. Circulation. 2019;139(8):1036-1046. doi:10.1161/CIRCULATIONAHA.118.035312

32. LaCroix AZ, Bellettiere J, Rillamas-Sun E, et al. Association of Light Physical Activity Measured by Accelerometry and Incidence of Coronary Heart Disease and Cardiovascular Disease in Older Women. JAMA Netw Open. 2019;2(3):e190419. doi:10.1001/jamanetworkopen.2019.0419

33. Liao C-M, Lin C-M. Life Course Effects of Socioeconomic and Lifestyle Factors on Metabolic Syndrome and 10-Year Risk of Cardiovascular Disease: A Longitudinal Study in Taiwan Adults. Int J Environ Res Public Health. 2018;15(10). doi:10.3390/ijerph15102178

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