Younger Women with AMI Less Likely to Present with Chest Pain Than Men

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Women are more likely than men to present without chest pain during myocardial infarction (MI) and to suffer higher in-hospital mortality, according to a new study published online February 21, 2012, ahead of print in the Journal of the American Medical Association. However, differences in clinical presentation by sex are attenuated with age.

For the observational study, John G. Canto, MD, MSPH, of the Watson Clinic (Lakeland, FL), and colleagues collected data from the National Registry of Myocardial Infarction from 1,143,513 MI patients treated between 1994 and 2006. The cohort was analyzed by sex (481,581 women and 661,932 men) and age in order to study trends in clinical presentation and mortality.

Overall, patients presented without chest pain 35.4% of the time, though atypical presentation was more prevalent among women than men (42.0% vs. 30.7%; P < 0.001). Multivariate analysis showed an interaction between age and sex such that sex-specific differences in presentation without chest pain became progressively less frequent with age (P < 0.001):

  • < 45 years: OR 1.30 (95% CI 1.23-1.36)
  • 45-54 years: OR 1.26 (95% CI 1.22-1.30)
  • 55-64 years: OR 1.24 (95% CI 1.21-1.27)
  • 65-74 years: OR 1.13 (95% CI 1.11-1.15)
  • 75-84 years: OR 1.03 (95% CI 1.02-1.04)

Overall, in-hospital mortality was higher for women (14.6%) than for men (10.3%). Among those with atypical presentation, women younger than 65 years had higher adjusted mortality rates compared with men of the same age. But among older patients, men with atypical presentation had the highest risk (table 1).

Table 1. In-Hospital Mortalitya in Patients Without Chest Painb




< 45 Years



45-54 Years



55-64 Years



65-74 Years



75 Years



a Adjusted for baseline characteristics, cardiovascular risk factors, medical history, cardiac history, and other variables.

b P < 0.001 for all comparisons. 

Even when presenting with chest pain, women still had higher mortality rates than men in the same age group, although the difference was smaller among older patients (table 2).

Table 2. In-Hospital Mortalitya in Patients with Chest Painb




< 45 Years



45-54 Years



55-64 Years



65-74 Years



75 Years



a Adjusted for baseline characteristics, cardiovascular risk factors, medical history, cardiac history, and other variables.
b P < 0.001 for all comparisons.

Tailor the Message

Dr. Canto told TCTMD in a telephone interview that these results challenge the conventional wisdom of how an MI typically presents by adding patient age to the equation.

“Our data show that [non-classic] presentations were more likely to be seen in women, especially young women, and they were at the highest risk for dying,” he said, adding that the data should be confirmed by additional prospective studies. “Perhaps we ought to be tailoring our heart attack message not only to men and women, but we ought to maybe say that younger women who have a heart attack may be at risk for atypical presentation and that their mortality is the highest of the high.”

Although the reasons for sex-based differences in MI symptom presentation are “largely unknown,” they probably stem from whatever factor is responsible for the higher mortality seen in young women, the authors say.

Moreover, Dr. Canto said, these differences likely account for why women are less likely to undergo invasive treatment. In the study, women without chest pain had lower rates of cardiac catheterization (49.7% vs. 59.3%), PCI (20.8% vs. 29.0%), and CABG (7.9% vs. 12.7%) than men without chest pain.

“If doctors and health care providers are not clear if a patient is having a heart attack because the symptoms are not classic, and because they are young you’re not thinking about a heart attack, it’s not surprising that the patients are not aggressively treated,” he said. “The doctors are just not sure whether they really in fact have a heart attack until all of the sudden all the blood work and tests come back.”

Some Headway But Not Enough

In an e-mail communication with TCTMD, Alexandra J. Lansky, MD, of the Yale School of Medicine (New Haven, CT), said “[t]his paper provides some potentially important insights into differences in presentation between men and women that may help explain the excess mortality seen in young women presenting with acute myocardial infarction, but it is far from giving us the answers we are looking for.”

For example, the definition of symptoms is “too simplistic, too subjective, not standardized, and [yet it is] the basis of the entire analysis,” Dr. Lansky asserted.

“We now are well aware of the complexity and intricacies of chest pain symptoms and sex differences,” she said. “Unless the patient had chest pain, additional symptoms were not extracted including shortness of breath, nausea, and vomiting (known to be important and relevant to women). Therefore, the results should not be interpreted to mean that 40% of women were asymptomatic. Other relevant symptoms may have been present but were not collected.”

Also, as the study is more than 6 years old, it “represents a historical dataset in terms of awareness of gender/sex specific issues of presentation, treatment, and awareness,” she noted, conceding the report “may well be of historic interest in current day practice.”

Dr. Lansky said the upcoming VIRGO trial, sponsored by the National Heart, Lung, and Blood Institute, will prospectively evaluate sex differences in clinical presentation, risk factors, biologics, genetics, outcomes and quality of life among a large population of AMI patients under 55 years of age. “VIRGO will provide definitive answers to many unresolved questions, to ultimately better [understand] the outcomes of AMI in young women,” she concluded.

Study Details

Regardless of age or sex, patients without chest pain were more likely to have diabetes and delayed hospital arrival and to present with Killip classification III and IV. Patients with chest pain were more likely to present with STEMI and anterior MI, and those without chest pain were more likely to present with NSTEMI.

Patients without chest pain were less likely to receive acute reperfusion therapies and less likely to receive them in a timely manner. They also were less apt to be given aspirin, other antiplatelet agents, heparin, and beta-blocker therapies during hospitalization; the disparities were especially evident in those older than 65 years. Patients with chest pain were more likely to receive cardiac catheterization and PCI, a difference that was especially evident among those younger than 65 years. Irrespective of chest pain, men had higher rates of diagnostic catheterization, PCI, and CABG than women.


Canto JG, Rogers WJ, Goldberg RJ, et al. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA. 2012;Epub ahead of print.



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  • Drs. Canto and Lansky report no relevant conflicts of interest.