Cardiovascular disease remains the leading cause of death for women in the United States, taking a woman’s life every 80 seconds. Recent studies investigating cardiovascular disease in women and men have demonstrated that cardiovascular disease manifests differently in women. In honor of American Heart Month, we are raising awareness about cardiovascular disease in women by summarizing recent studies relating to cardiovascular disease risk factors, primary prevention, and cardiac imaging.

Differences in Cardiovascular Disease Risk Factors

The American Heart Association estimates that 80% of cardiovascular disease can be prevented through healthy behaviors. Risk factors–such as tobacco usage, high cholesterol, obesity, and high blood pressure–increase a person’s likelihood of developing cardiovascular disease within the course of their life. While both women and men share traditional cardiovascular risk factors, several women-specific factors have demonstrated an increase likelihood of cardiac events.

In 2020, the American College of Cardiology (ACC) Cardiovascular Disease in Women Committee summarized new recommendations for the primary prevention of cardiovascular disease in women. The “Updated Recommendations for Primary Prevention of CVD in Women” highlights several unique factors that increase cardiovascular disease risk in female populations, including:

  • Pregnancy-associated conditions, such as hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm birth, and pregnancy loss
  • Premature menopause
  • Polycystic ovarian syndrome
  • Sex-related differences in cardiovascular medications
  • Psychosocial factors such as depression, anxiety, and acute or chronic emotional stress
These guidelines attempt to bridge the treatment gap to help lower cardiovascular risk in women.

Risk Scores for Primary Prevention

Cardiovascular risk scoring is used to estimate the chances that a patient will experience a cardiac event based on various risk factors. Clinicians often use risk scoring to then guide primary prevention. However, studies have demonstrated that risk scores often inaccurately predict cardiovascular disease, particularly in female populations.

A study published in the Journal of the American Heart Association investigated the applicability of primary prevention risk scores in patients with signs and symptoms of ischemia but no obstructive CAD. The study included 433 women with accessible risk data for six risk scores, including the Framingham Risk Score, Reynolds Risk Score, Adult Treatment Panel III, Atherosclerotic Cardiovascular Disease, Systematic Coronary Risk Evaluation, and Cardiovascular Risk Score 2. In the study, all six scores failed to accurately predict risk, and five out of six risk scores classified a large portion of women as low risk for cardiovascular disease [1].

Similar results were demonstrated in a study by researchers in the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. The study results, published in JAMA Internal Medicine, showed that new risk equations over-predicted risk in three external validation cohorts [2]. Improved methods for guiding the primary prevention of cardiovascular disease in women are necessary to help lower cardiovascular risk.

Sex Differences in Coronary CTA

Coronary computed tomographic angiography (CTA) is a preferred non-invasive test for screening CAD in patients. When interpreting coronary CTA scans, recent studies have recognized the importance of understanding images in the context of sex-related differences.

A study published in JACC: Cardiovascular Imaging suggests that plaque characteristics in female patients with suspected CAD may present differently than in male patients. In the study, researchers examined the role of sex in compositional plaque volume in patients with CAD. Researchers analyzed 1,255 patients with CAD who had undergone at least two coronary CTA exams. The findings revealed that compositional plaque volume progression differed in women as compared to men [3].

Researchers have also discovered nuances in cardiovascular disease in women when using non-invasive CT-FFR as a diagnostic tool for patients with CAD. Researchers of the ADVANCE trial evaluated 4,373 patients with stable CAD who underwent both CCTA and CT-FFR to examine sex-related differences. Study results demonstrated that CT-FFR had higher values for the same degree of stenosis in women [4]. Additionally, female study participants had similar rates of invasive coronary angiography to male participants, but less obstructive coronary artery disease and revascularization at catheterization.

Could Coronary Artery Calcium (CAC) Scoring Guide Primary Prevention?

Evidence suggests that coronary artery calcium (CAC) scoring could be effective in risk stratification. Recent research published in Circulation: Cardiovascular Imaging aimed to determine the long-term prognosis of asymptomatic women and men classified at low-intermediate risk undergoing CAC scoring. In the study, 2,363 asymptomatic women and men with traditional risk factors underwent CAC scanning. The study findings demonstrate that CAC may effectively risk-stratify women who are slightly lower risk than those conventionally targeted to undergo imaging for screening, including those with an intermediate Framingham Risk Score [5]. CAC scoring could add value to the primary prevention of cardiovascular disease.

Raising Awareness & Advocating for Women

Each of these studies has contributed to accelerating progress in better treating women with cardiovascular disease. Additional research focused on female populations presenting with cardiovascular disease is necessary to help improve prevention, diagnosis, and treatment.

To help make a difference and support progress, consider getting involved in the following ways:

References

[1] Sedlack T, Herscovici R, Cook-Wiens G, Handberg E, Wei J, Shufelt C, Bittner V, Reis SE, Reichek N, Pepine C, Noel Bairey Merz C. Predicted Versus Observed Major Adverse Cardiac Event Risk in Women with Evidence of Ischemia and No Obstructive Coronary Artery Disease: A Report from WISE (Women’s Ischemia Syndrome Evaluation). Journal of the American Heart Association. 2020 Apr, e013234.

[2] Cook NR, Ridker PM. Further Insight into the Cardiovascular Risk Calculator: The Roles of Statins, Revascularizations, and Underascertainment in the Women’s Health Study. JAMA Intern Med. 2014;174(12):1964-1971. doi:10.1001/jamainternmed.2014.5336
[3] Lee SE, Sung JM, Andreini D, Al-Mallah MH, Budoff MJ, Cademartiri F, Chinnaiyan K, Choi JH, Chun EJ, Conte E, Gottlieb I, Hadamitzky M, Kim YJ, Lee BK, Lepsic JA, Maffei E, Marques H, Goncalves PA, Pontone G, Shin S, Stone PH, Samady H, Virmani R, Narula J, Berman DS, Shaw LJ, Bax JJ, Lin FY, Min JK, Chang HJ. Sex Differences in Compositional Plaque Volume Progression in Patients. With Coronary Artery Disease. 2020 Nov;13(11):2386-2396.
[4] Fairbairn TA, Dobson R, Hurwitz-Koweek L, Matsuo H, Norgaard BL, Rønnow Sand NP, Nieman K, Bax JJ, Pontone G, Raff G, Chinnaiyan KM, Rabbat M, Amano T, Kawasaki T, Akasaka T, Kitabata H, Binukrishnan S, Rogers C, Berman D, Patel MR, Douglas PS, Leipsic J. Sex Differences in Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve: Lessons From ADVANCE. JACC Cardiovasc Imaging. 2020 Dec;13(12):2576-2587. doi: 10.1016/j.jcmg.2020.07.008. Epub 2020 Aug 26. PMID: 32861656.
[5] Kelkar AA, Schultz WM, Khosa F, Schulman-Marcus J, O’Hartaigh BW, Gransar H, Blaha MJ, Knapper JT, Berman DS, Quyyumi A, Budoff MJ, Callister TQ, Min JK, Shaw LJ. Long-Term Prognosis After Coronary Artery Calcium Scoring Among Low-Intermediate Risk Women and Men. Circ Cardiovasc Imaging. 2016 Apr;9(4):e003742. doi: 10.1161/CIRCIMAGING.115.003742. PMID: 27072301.