Despite an overall reduction in the incidence of myocardial infarction (MI) and associated mortality in the general population, a growing body of research suggests increasing MI rates and worsening outcomes among individuals younger than 55 years.1,2 To elucidate these trends, numerous studies have focused specifically on the reported sex-based disparities in MI risk factors and outcomes in this patient population.
“Myocardial infarction rates are going up in young women, and cardiovascular mortality is no longer improving in young people in the United States,” Viola Vaccarino, MD, PhD, said in an interview with Cardiology Advisor. Dr Vaccarino is the Wilton Looney Professor of Cardiovascular Research in the Rollins School of Public Health at Emory University in Atlanta and professor in the division of cardiology at the Emory University School of Medicine. She published a paper on the increasing acute MI (AMI) rates among young women in a 2019 issue of Circulation.3
A 2019 study analyzed data from the Atherosclerosis Risk in Communities (ARIC) Surveillance study and observed an increase in the annual incidence of AMI hospitalizations among young women (aged 35-54 years) from 1995 to 2014, while AMI incidence decreased among young men.2
Adjusted analyses further demonstrated that young women are less likely than young men to receive coronary revascularization (relative risk [RR], 0.79; 95% CI, 0.71–0.87), nonaspirin antiplatelets (RR, 0.83; 95% CI, 0.75–0.91), lipid-lowering therapies (RR, 0.87; 95% CI, 0.80–0.94), coronary angiography (RR, 0.93; 95% CI, 0.86–0.99), and beta blockers (RR, 0.96; 95% CI, 0.91–0.99).
While this study found comparable rates of 1-year all-cause mortality in women and men (hazard ratio [HR], 1.10; 95% CI, 0.83–1.45), a 2022 study4 described in the Journal of Clinical Medicine found an 84.3% higher 3-year all-cause mortality rate in young women (<65 years) vs young men (<55 years) after AMI (adjusted HR [aHR], 1.843; 95% CI, 1.098–3.095). Conversely, elderly women show a 20.4% lower mortality rate compared to elderly men (aHR, 0.796; 95% CI, 0.682–0.929).
Research published in 2020 in the European Heart Journal reported similar disparities in invasive procedures and guideline-based treatment approaches provided to young (<50 years) women vs men. While there was no significant difference in cardiovascular mortality between women and men following discharge, women demonstrate greater all-cause mortality (aHR, 1.63; P =.01) after a median follow-up period of 11.2 years.5
In a multicenter prospective study reported in August 2021 in Frontiers in Cardiovascular Medicine, investigators observed a longer duration of time from symptom onset to hospital admission among young (≤45 years) women compared to young men.6 Additionally, the risk for in-hospital adverse events is higher for young women vs men (adjusted odds ratio [aOR] for death, 5.767; 95% CI, 1.580–21.049; P =.0080; aOR, for the composite of death, re-infarction, and stroke, 3.981; 95% CI, 1.150–13.784; P =.0292). Among patients who are discharged, the 2-year cumulative incidence of death is higher for women vs men (3.8 vs 1.4%; P =.0412).
In a matched case-control study published in May 2022 in JAMA Network Open, researchers examined sex-specific risk factors for MI in a sample of 2,264 adults aged younger than 55 years who experienced a first acute MI compared with 2,264 matched control participants.7
Most of the factors that collectively contributed to roughly 85% of the total AMI risk showed stronger associations for young women, including:
- diabetes (OR, 3.59; 95% CI, 2.72-4.74 in women vs OR, 1.76; 95% CI,1.19-2.60 in men)
- depression (OR, 3.09; 95% CI, 2.37-4.04 in women vs OR, 1.77; 95% CI, 1.15-2.73 in men)
- hypertension (OR, 2.87; 95% CI, 2.31-3.57 in women vs OR, 2.19; 95% CI, 1.65-2.90 in men)
- currently smoking (OR, 3.28; 95% CI, 2.65-4.07 in women vs OR, 3.28; 95% CI, 2.65-4.07 in men)
- family history of premature MI (OR, 1.48; 95% CI, 1.17-1.88 in women vs OR, 2.42; 95% CI, 1.71-3.41 in men)
Hypercholesterolemia shows a stronger association in young men (OR, 1.02; 95% CI, 0.81-1.29 in women vs OR, 2.16; 95% CI, 1.49-3.15 in men). Low household income represents an additional risk factor in both groups (OR, 1.02; 95% CI, 0.81-1.29 in women vs OR, 2.16; 95% CI, 1.49-3.15 in men).
As many of these risk factors are potentially modifiable, the results point to the need for sex-specific strategies to modify these risk factors to prevent AMI in young adults, according to the authors.
The disparities in MI rates and outcomes are “especially marked in rural communities, suggesting that economic deprivation may be affecting cardiovascular health, especially among young women,” Dr Vaccarino noted.8 Related factors may include reduced access to prevention services and affordable health care in general, environmental factors such as lack of access to fresh food and safe places to walk, and psychosocial stress due to the multiple family demands that women often fill.
“Clinicians should offer prevention services to women beginning at a younger age and offer resources that can provide them the support they need to stay healthy or recover if they already developed a myocardial infarction,” she said. “These services are especially needed in low resource settings.”
Cardiology Advisor interviewed the lead authors of 2 of the recent studies7,5 on MI in young women to learn more about the concerning trends observed in this population: Yuan Lu, ScD, researcher and assistant professor in the section of cardiovascular medicine at Yale School of Medicine in New Haven, Connecticut; and Ersilia M. DeFilippis, MD, a specialist in advanced heart failure and transplant cardiology and assistant professor of medicine at Columbia University Irving Medical Center in New York.
What are your thoughts about findings of disparities in MI risk factors and outcomes in young women, and do they align with your observations in practice?
Dr Lu: Our study identified sex differences in AMI risk factors as well as the strength of associations between these risk factors and AMI among young adults. Traditional cardiovascular risk factors such as hypertension and diabetes had stronger associations in women vs men, with significant interactions by sex. This observation is consistent with prior studies, including the INTERHEART study9 of older populations, and we provided an independent validation of these findings in young adults.
Moreover, we showed that current smoking and gender-related characteristics including low income and depression were linked to greater risk in women compared to men. These findings align with our observations in practice. In clinical practice, we noticed that young women admitted for AMI are more likely to have depression, which partially contributes to the higher mortality and poorer health status after AMI in young women.
Dr DeFilippis: Unfortunately, sex disparities in outcomes have been demonstrated across a variety of cardiovascular conditions, so while our findings were disappointing, they were not surprising. Although the most common presentation of MI in women is chest pain, they also may have atypical presentations (including shortness of breath, palpitations, and fatigue) that could lead to delayed diagnosis.5 I know women who have been told they were having an anxiety attack when in fact they were having manifestations of ischemic heart disease or heart failure.
What are the possible mechanisms driving these disparities?
Dr Lu: We found that socioeconomic and psychological factors have an important role in the development of AMI in young women. Although the mechanisms by which low socioeconomic status and low social support negatively affect patient outcomes remain unclear, numerous psychological, behavioral, and physiological theories have been proposed. These range from poor self-care and negative health behaviors to increased financial strain and elevated stress responses.
Indeed, we found that patients with low socioeconomic status had a higher prevalence of all cardiovascular factors and more financial instability than patients with moderate or high socioeconomic status. Depression also plays an intimate role in the development of AMI in young women, and depression was strongly associated with poorer functional status and mental health status after AMI.
Dr DeFilippis: We do understand that certain traditional cardiovascular risk factors may have a greater risk for future CV events in women than in men. Additionally, the mechanisms underlying ischemic heart disease may be different in women, including microvascular disease, coronary spasm, and spontaneous coronary artery dissection in addition to classic plaque rupture. These may require further testing or imaging modalities.
Despite this, we know that few women with abnormal stress tests get referred for diagnostic angiography or have a change in medication therapies. Therefore, underdiagnosis and undertreatment likely also result from implicit bias on the part of health care providers.
Additionally, we know that awareness of heart disease as the leading cause of death among women declined from 2009 to 2019, highlighting a need for increased education of women so they can recognize their symptoms and advocate for themselves.10
What are the relevant recommendations for clinicians?
Dr Lu: As a first step, clinicians need to be aware of the sex difference in risk factors for AMI in young women and pay attention to screening these risk factors when providing care for young women. Then they can refer the patient to targeted interventions to address these risk factors if indicated.
Dr DeFilippis: To paraphrase William Osler, “Listen to the patient; she is telling you the diagnosis.” Since women may have atypical presentations, it is important to have a high index of suspicion. Additionally, all physicians should take an obstetric and gynecologic history on their female patients. We know that sex-specific risk factors for CVD include a history of pre-eclampsia or premature ovarian failure among others. This can help to risk-stratify women in addition to traditional cardiovascular risk factors.
What other measures may be needed to reduce these disparities?
Dr Lu: Raising awareness about cardiovascular disease risk in young women is the first necessary step to address these disparities. Then, screening risk factors including family history and psychological factors are needed to further identify high-risk patients for AMI. Documentation of family history and social determinants of health in the electronic health records will help clinicians to better understand and risk-stratify their patients. Finally, the development of more individualized risk prediction will enable more effective application of preventive therapies in young women.
Dr DeFilippis: Needed measures include targeting social determinants of health and development of sex-specific guidelines and sex-specific risk calculators.11
Increased education of women regarding heart disease as the leading cause of death is also needed. Unfortunately, many women with the lowest awareness rates are those with lesser education and low income, and those who are racial and ethnic minorities. Therefore, this education must include partnership with local communities, including in local gyms, schools, and faith-based organizations.
There is also a need to improve the diversity of women in clinical trials of ischemic heart disease. We know that increased diversity of clinical trial leadership is associated with increased recruitment of women into cardiovascular trials, so this represents an additional need.
- Wu WY, Berman AN, Biery DW, Blankstein R. Recent trends in acute myocardial infarction among the young. Curr Opin Cardiol. 2020;35(5):524-530. doi:10.1097/HCO.0000000000000781
- Arora S, Stouffer GA, Kucharska-Newton AM, et al. Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction. Circulation. Published online November 11, 2019. doi:10.1161/CIRCULATIONAHA.118.037137
- Vaccarino V. Myocardial infarction in young women. Circulation. Published online February 19, 2019. doi:10.1161/CIRCULATIONAHA.118.039298
- Song PS, Kim MJ, Seong SW, et al; Kamir-Nih Investigators. Gender differences in all-cause mortality after acute myocardial infarction: evidence for a gender-age interaction. J Clin Med. 2022;11(3):541. doi:10.3390/jcm11030541
- DeFilippis EM, Collins BL, Singh A, et al. Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry. Eur Heart J. Published online October 13, 2020. doi:10.1093/eurheartj/ehaa662
- Lv J, Ni L, Liu K, et al. Clinical characteristics, prognosis, and gender disparities in young patients with acute myocardial infarction. Front Cardiovasc Med. Published online August 22, 2021. doi:10.3389/fcvm.2021.720378
- Lu Y, Li SX, Liu Y, et al. Sex-specific risk factors associated with first acute myocardial infarction in young adults. JAMA Netw Open. Published online May 3, 2022. doi:10.1001/jamanetworkopen.2022.9953
- Tran P, Tran L. Influence of rurality on the awareness of myocardial infarction symptoms in the US. Ther Adv Cardiovasc Dis. Published online December 4, 2019. doi:10.1177/1753944719891691
- Anand SS, Islam S, Rosengren A, et al; INTERHEART Investigators. Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur Heart J. Published online March 10, 2008. doi:10.1093/eurheartj/ehn018
- Cushman M, Shay CM, Howard VJ, et al; American Heart Association. Ten-year differences in women’s awareness related to coronary heart disease: Results of the 2019 American Heart Association National Survey: A Special Report From the American Heart Association. Circulation. Published online September 19, 2021. doi:10.1161/CIR.0000000000000907
- DeFilippis EM, Van Spall HGC. Is it time for sex-specific guidelines for cardiovascular disease? J Am Coll Cardiol. Published online July 5, 2021. doi:10.1016/j.jacc.2021.05.012