ÐÓ°ÉÂÛ̳

Cardiovascular disease (CVD) is the leading cause of death in women.^1,2 However, women are much less likely than men to be assessed for CVD risk based on guidelines and many risk factors that are unique to women may be overlooked.^1,3-5 Notably, less than half of all primary care physicians consider CVD a top concern for women after breast health and weight.¹

This article discusses CVD, traditional risk factors, risk-enhancing factors, and guideline recommendations for assessing CVD risk in women.

Epidemiology of CVD in women

In 2019, about 1 of every 5 deaths in women were due to CVD.² The population-adjusted risk mortality from CVD was estimated at 21% for women compared to 15% for men.³ Notably, 90% of women have at least 1 risk factor for atherosclerotic CVD (ASCVD).³

Overall, about 6% of women age 20 and older have coronary heart disease (CHD).⁶ The prevalence of CHD varies with race/ethnicity, being higher in White, Black, and Hispanic women (about 6% overall) than Asian women (3%).⁶ In the United States, heart disease is the leading cause of death for Black and White women; equal leading cause of death (with cancer) for American Indian and Alaskan Native women; and second leading cause of death (after cancer) for Hispanic and Asian or Pacific Islander women.⁶

Despite increased awareness over the past decades, only about half (56%) of women realize that the number 1 cause of death in most women is heart disease.⁶

Traditional CVD risk factors in women

Women and men share traditional risk factors for CVD, with the 3 most common risk factors being hypertension, high low-density lipoprotein-cholesterol (LDL-C), and smoking.^6-8 Approximately half of all people in the United States have at least 1 of these 3 risk factors.⁶ Insulin resistance is a risk factor for CVD, and other risk factors common to women and men related to insulin resistance include^6-9

• Diabetes
• Being overweight or obese
• Eating an unhealthy diet
• Physical inactivity
• Excess alcohol consumption

Although traditional risk factors are common to women and men, their effects and symptoms (eg, myocardial infarction, MI) differ between sexes (see Sidebar).¹

CVD risk-enhancing factors for women

The 2018 American Heart Association (AHA)/American College of Cardiology (ACC)-Multi-Society Cholesterol guideline and 2019 ACC/AHA Primary Prevention of CVD guideline introduced the concept of ¡°risk-enhancing factors¡± that are specific to women (see below).^7,13 Risk-enhancing factors are associated with an increased risk of ASCVD beyond the traditional risk factors. If present, these factors indicate that increased risk should be mitigated through more intensive lifestyle interventions or statin therapy for primary prevention.^7,13-15

Several categories of risk-enhancing factors are shared by women and men,¹⁶ although, autoimmune disease predominantly affects women (see below).⁴

In addition, adverse pregnancy outcomes occur in 10% to 20% of all pregnancies and are associated with a 1.8- to 4.0-fold risk of future CVD.¹⁷ The American College of Obstetricians and Gynecologists (ACOG) recommends that women with an adverse pregnancy outcome (see below) and/or cardiovascular risk factors undergo cardiovascular risk screening within 3 months postpartum.¹⁷

Examples of CVD-risk enhancing factors specific to women, shared between men and women, and related to pregnancy are given below.

CVD risk-enhancing factors specific to women include

• Polycystic ovarian syndrome (PCOS)¹⁴
  • Higher prevalence of hypertension, central adiposity, insulin resistance, dyslipidemia, and metabolic syndrome¡ªall of which increase the risk of CVD.
  • Higher body-mass indices, waist circumferences, blood pressure, glucose levels, and hyperlipidemia at the time of PCOS diagnosis are associated with greater CVD risk.
• Premature menopause/ovarian failure (menopause or loss of ovarian function prior to 40 or 45 years old [average age for menopause onset is 51 years])¹⁴
  • Menopause at an age younger than 45 years (compared to ¡Ý45 years): 1.5-fold increased risk of CHD.
  • Premature ovarian failure: 1.6-fold increased risk of CVD, 1.7-fold increased risk of CVD mortality.
• Premature menarche (¡Ü10 years of age): 1.3-fold increased risk of CHD.¹⁴
• Late menarche (¡Ý17 years of age): 1.2-fold increased risk of CHD.¹⁴
• Hormone-based contraceptive methods¹⁴
  • Can affect the lipid profile and thereby CVD risk (eg, estrogen-based contraceptives typically elevate triglycerides and should be used with caution in women with elevated triglycerides, and contraceptives with androgenic components such as norgestrel may elevate LDL-C and decrease HDL-C levels).
• Breast cancer history and associated treatments¹⁴
  • Shared risk factors between cancer and CVD include smoking, obesity, and hypertension.
  • Radiation to the left breast is associated with an increased risk of CHD.
  • Chemotherapeutic agents such as anthracyclines and trastuzumab increase the risk of cardiomyopathy and heart failure (HF).
• Recurrent miscarriages¹⁴
  • Two miscarriages: 1.7-fold increased risk of CHD.
  • Three or more miscarriages: 3.2-fold increased risk of CHD.

CVD risk-enhancing factors shared by women and men include

• Race and genetics (eg, family history of premature ASCVD)¹⁶
• Lipid-related (eg, primary hypercholesterolemia)¹⁶
• High-risk medical conditions (eg, metabolic syndrome, insulin resistance)¹⁶
• Biomarkers (eg, elevated lipoprotein(a) level)¹⁶
• Autoimmune/systemic inflammatory diseases⁴
  • Disproportionally affect women (female:male ratio, rheumatoid arthritis 2.5:1; systemic lupus erythematosus 9:1).
  • Associated with increased CVD morbidity and mortality¡ªrheumatoid arthritis is associated with an approximately 50% increased risk of cardiovascular events and death.?

CVD risk-enhancing factors related to pregnancy include

• Pre-eclampsia: 4-fold increased risk of HF; 2-fold increased risk of CHD¹⁴
• Hypertensive disorders of pregnancy (gestational hypertension): 2.2-fold increased risk of CVD; 5.6-fold increased risk of hypertension¹⁴
• Gestational diabetes: 8-fold increased risk of developing type 2 diabetes mellitus; 2-fold increased risk of future cardiovascular events¹⁴
• Preterm delivery (birth of a baby at <37 weeks gestational age): 1.4-fold increased risk of CVD; overall increased risk of developing chronic hypertension, diabetes, and hypercholesterolemia¹⁴

Interestingly, lactation is a CVD risk-reducing factor.¹⁴ Breastfeeding is thought to aid in reversing the metabolic changes of insulin resistance, dyslipidemia, and accumulation of fat mass that take place during pregnancy.

Guideline recommendations for assessing CVD risk in women

For both men and women, the 2019 ACC/AHA Guideline on the Primary Prevention of CVD and the 2018 AHA/ACC/Multi-Society Cholesterol Guidelines recommend consideration of risk-enhancing factors for individuals who are at borderline- and intermediate-risk, after estimating their 10-year atherosclerotic cardiovascular disease (ASCVD) risk.^7,13 The presence of ¡Ý1 risk-enhancing factor may indicate a higher risk category and favor initiation or intensification of statin therapy.^13,16 Risk-enhancing factors should be integrated with other information and patient preferences to inform clinical decision making; guidelines recommend that patients should be informed of their personal ASCVD risk and risk-enhancing factors before discussing therapeutic options.¹⁶ Lifetime risk can be assessed for individuals 20 to 59 years of age. Persons with a low 10-year risk but high lifetime risk may be treated with aggressive lifestyle modifications, as recommended by the 2018 AHA/ACC Multi-society cholesterol management guideline and the 2019 ACC/AHA Prevention of CVD guideline.¹³

Women who have a pregnancy or nonpregnancy CVD risk factor (eg, patients with gestational hypertension) should receive closer monitoring for hypertension after pregnancy.¹⁴

Guidelines for assessing CVD risk in men are similar to those for women but also take into account risk-enhancing factors unique to men (eg, erectile dysfunction, low testosterone level).

Traditional CVD risk factors in women and men

Certain CVD risk factors affect women differently than men¹

• CVD risk among people with type 1 or type 2 diabetes is greater for women than for men (19% vs 10%). Notably, women with diabetes are less likely to be treated for CVD risk factors than are men with diabetes.
• Among persons older than 65, women are more likely to be hypertensive than men, but only 29% of women have adequate blood pressure management (compared to 41% of men).
• For women, the factor that imparts the greatest CVD risk is hypercholesterolemia (47%).
• Obese women have a higher coronary artery disease risk compared with obese men (64% vs 46%).
• Psychosocial factors (eg, depression) are associated with higher CVD mortality in women than men (45% vs 29%).
• CVD risk for women who smoke is 25% greater than for men who smoke.

Symptoms of myocardial ischemia/infarction in women

While many symptoms of a heart attack are similar in men and women, some are more common in or unique to women. Women are more likely than men to have heart attacks that do not show obvious symptoms; these are called silent heart attacks.¹⁰

Symptoms common to men and women

• Pain, pressure, or squeezing in chest¹¹
• Radiation of pain to neck, shoulder, back, arm, jaw¹¹
• Palpitations¹¹
• Difficulty in breathing¹¹
• Heartburn, nausea, vomiting¹¹
• Cold sweats, clamminess¹¹
• Dizziness¹¹

Symptoms more common in women?(generally, women report milder symptoms than men¹¹)

• Sudden onset of weakness, shortness of breath, fatigue, feeling of systemic illness (without chest pain)¹¹
• Mild discomfort/pain in back, chest, arm, neck, or jaw (without chest pain)^10,11
• Pain or pressure in the lower chest or upper abdomen¹²
• Nausea or vomiting¹²
• Indigestion^10,12
• Extreme fatigue^10,12

How the laboratory can help

Quest offers testing for risk assessment, diagnosis, and management of cardiovascular disease, as well as metabolic and medical conditions that affect the risk of cardiovascular disease in women and men.

Additional information is available at

References

1. Vogel B, Acevedo M, Appelman Y, et al. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet. 2021;397(10292):2385-2438. doi:10.1016/S0140-6736(21)00684-X

2. Lower your risk for the number 1 killer of women. Centers for Disease control and Prevention. Reviewed February 4, 2022. Accessed June 31, 2022.??

3. Brown HL, Warner JJ, Gianos E, et al. Promoting risk identification and reduction of cardiovascular disease in women through collaboration with obstetricians and gynecologists: a presidential advisory from the American Heart Association and the American College of Obstetricians and Gynecologists. Circulation. 2018;137(24):e843-e852. doi:10.1161/CIR.0000000000000582

4. Geraghty L, Figtree GA, Schutte AE, et al. Cardiovascular disease in women: from pathophysiology to novel and emerging risk factors. Heart Lung Circ. 2021;30(1):9-17. doi:10.1016/j.hlc.2020.05.108

5. Maffei S, Guiducci L, Cugusi L, et al. Women-specific predictors of cardiovascular disease risk - new paradigms. Int J Cardiol. 2019;286:190-197. doi:10.1016/j.ijcard.2019.02.005

6. Women and heart disease. Centers for Disease Control and Prevention. Reviewed January 31, 2020. Accessed June 16, 2022.

7. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678

8. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-952. doi:10.1016/S0140-6736(04)17018-9

9. Adeva-Andany MM, Mart¨ªnez-Rodr¨ªguez J, Gonz¨¢lez-Luc¨¢n M, et al. Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab Syndr. 2019;13(2):1449-1455. doi:10.1016/j.dsx.2019.02.023

10. Heart attack symptoms. Office on Women¡¯s Health. US Department of Health and Human Services. Updated February 17, 2021. Accessed June 31, 2022.

11. Keteepe-Arachi T, Sharma S. Cardiovascular disease in women: understanding symptoms and risk factors. Eur Cardiol. 2017;12(1):10-13. doi:10.15420/ecr.2016:32:1

12. Symptoms of a heart attack in women and men. American Heart Association. Reviewed October 9, 2020. Accessed June 31, 2022. .

13. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143. doi:10.1161/CIR.0000000000000625

14. Agarwala A, Michos ED, Samad Z, et al. The use of sex-specific factors in the assessment of women's cardiovascular risk. Circulation. 2020;141(7):592-599. doi:10.1161/CIRCULATIONAHA.119.043429

15. Mehta LS, Watson KE, Barac A, et al. Cardiovascular disease and breast cancer: where these entities intersect: a scientific statement from the American Heart Association. Circulation. 2018;137(8):e30-e66. doi:10.1161/CIR.0000000000000556

16. Agarwala A, Liu J, Ballantyne CM, Virani SS. The use of risk enhancing factors to personalize ASCVD risk assessment: evidence and recommendations from the 2018 AHA/ACC Multi-society Cholesterol Guidelines. Curr Cardiovasc Risk Rep. 2019;13(7):18. doi:10.1007/s12170-019-0616-y

17. Cho L, Davis M, Elgendy I, et al. Summary of updated recommendations for primary prevention of cardiovascular disease in women: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75(20):2602-2618. doi:10.1016/j.jacc.2020.03.060

Published date: Aug 2022