More Women Still Die of AMI as Tools Go Unused, Overlooked

Shelley Wood

July 25, 2014

NEW HAVEN, CT — Not for the first time, researchers are trying to get to the bottom of a long-running mystery: why do women seem to face a higher risk of dying after MI[1]? Yale researchers, reviewing nearly 50 years of published research, opted to focus on long-term mortality differences and say their findings offer clues as to what new research is needed to close the "gender gap."

An accompanying editorial, however, argues that although new research is welcome, clinicians already have critical tools in hand to better predict which women are at risk for MI and to diagnose AMI in a timely manner, potentially leading to better survival[2].

The problem? They're not using them.

Emily Bucholz (Yale University School of Medicine, New Haven, CT) and colleagues set out to review studies of long-term mortality post-MI in women vs men—something they believe no previous study has done—ultimately zeroing in on 39 studies with at least five years of follow-up.

Their original intention, Bucholz confirmed to heartwire , was to conduct a meta-analysis, but heterogeneity across studies (in terms of patient populations, methodology, risk adjustment, and results) left them instead with information only for a "systematic review."

"We did consider subgroup analyses, but these were also too heterogeneous to calculate a meaningful summary risk estimate," she added.

Findings Mirror Those of Shorter Studies

Their review ultimately corroborates many of the observations made in previous smaller analyses and studies with shorter follow-up:

  • Mortality differences post-MI are attenuated after adjustment for age; women tend to present with AMI at an older age than men.

  • Women are more likely to have significant comorbidities than are men, particularly diabetes, congestive heart failure, depression, and renal dysfunction.

  • When studies are adjusted for revascularization procedures, which are used less commonly in women, mortality risk is more similar between men and women.

In one heartening and novel observation, Bucholz et al report that the mortality gap between men and women appears to have narrowed slightly over the years.

A secondary observation from this review is also worth emphasizing, Bucholz et al write: women typically made up just one-third of the patients in the studies reviewed, likely due in part to the exclusion of older patients.

"The underrepresentation of women in many of these studies is an important finding in its own right," they note.

Different Diagnostic Criteria Are Ignored

That's a point also picked up in the editorial by Dr Noel Bairey Merz (Cedars-Sinai Medical Center, Los Angeles, CA), who highlights an even bigger challenge: having clinicians take sex differences seriously and incorporate any opportunities to mitigate these differences into daily practice.

The "most objective criteria" for diagnosing AMI are cardiac biomarker elevations, Bairey Merz notes. Studies dating back two and a half decades established that MI in women is defined by a lower threshold, yet these have been "long ignored in both science and practice," resulting in lower detection of AMI in women, she writes.

In studies of diagnostic ECGs, it has also been suggested that sex differences play a role, with ECGs being "less likely to be diagnostic for obstructive CAD in women." Other ECG differences between men and women have been identified in studies that Bairey Merz details in her editorial, yet they have "not been repeated or incorporated into clinical care."

In fact, advice to use sex-specific values for cardiac troponin and CKMB, as well as information on differences in ECG reference standards between men and women, are included in the ESC/ACCF/AHA/WHF Expert Consensus Document: Third Universal Definition of MI, published in 2012. Yet these key differences are, "to my knowledge, not known or discussed," Bairey Merz told heartwire .

Bairey Merz points to another area where management and treatment of male and female patients is likely having an influence on AMI survival at a later stage—namely, at the time of ischemic heart disease diagnosis. Here, she notes, women are less likely to be found to have obstructive coronary artery disease at the time of coronary angiography, and they are more likely to have coronary microvascular dysfunction—something "not routinely recognized with current male-pattern diagnostic angiographic strategies" yet known to carry adverse prognosis.

"Existing diagnostic AMI and CHD strategies developed in men, for men, and by men fail to diagnose approximately 20% to 30% of women with ischemic heart disease," she writes. It's high time physicians start closing the AMI diagnosis and outcomes gap between men and women, without waiting for new research by incorporating "the well-documented non–chest-pain symptoms into emergency-department and outpatient suspected ACS/AMI protocols," Bairey Merz told heartwire .

Bucholz had no conflicts of interest. Disclosures for the coauthors are listed in the paper. Bairey Merz reported "industry relationships in the past two years, all <$10,000: Gilead (grant review), Japanese Circulation Society (speaker), snf Bristol-Meyers Squibb (DSMB)."


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