Women-Specific Goalposts Urged for Coronary Bypass Surgery

Gender disparities in outcomes after coronary artery bypass grafting (CABG) might be addressed by sex-specific biomarker thresholds for perioperative myocardial injury, researchers suggested from a retrospective study.

Compared with men, women tended to release less high-sensitivity cardiac troponin (hs-cTn) and creatine kinase-myocardial band (CK-MB) after bypass surgery but experienced more 30-day major adverse cardiovascular events (MACE), based on records from two tertiary university centers.

Theoretically, between a general troponin cutoff of 206.07 times upper reference limit (URL) and a female-specific cutoff of 94.36 times URL, women who missed the former but not the latter were at increased risk of MACE (OR 3.78, 95% CI 1.03-13.08) and death (OR 4.98, 95% CI 1.20-20.61) compared with peers who stayed below both thresholds, reported Can Gollmann-Tepeköylü, PhD, of Medical University of Innsbruck in Austria, and colleagues in the Annals of Thoracic Surgery.

Study investigators defined MACE as the composite of myocardial infarction, all-cause mortality, and repeat revascularization within 30 days. In line with prior work, the women in this study compared with men experienced disproportionately more 30-day MACE (4.5% vs 2.4%, P=0.003) and 30-day mortality (3.0% vs 1.3%, P=0.003).

“We believe identifying underdiagnosed perioperative myocardial infarction early in women might counteract the care disparity we obviously still have after CABG surgery,” the authors wrote.

“These thresholds are clearly above thresholds used in consensus statements of recommending values >10, ≥35, and ≥70 times the URL,” the team noted. “However, most definitions additionally ask for new signs of ischemia in ECG, echocardiography or angiography and consequently increase the predictive value markedly.”

As for CK-MB, Gollmann-Tepeköylü’s group reported smaller discrepancies between men and women that translated into optimal thresholds of 3.02 times URL for men and 2.82 times URL for women. Women who met the female-specific but not general CK-MB cutoff for myocardial injury had more 30-day MACE (OR 10.04, 95% CI 2.07-48.75) and death (OR 13.59, 95% CI 2.66-69.47), as was the case for troponin.

CK-MB release currently has to reach >5 to >20 times URL to meet criteria for a diagnosis of perioperative myocardial infarction or myocardial injury after CABG.

The existing literature already suggests important sex differences in the release kinetics of cardiac biomarkers in the healthy population, related in part to factors such as body composition and fat distribution, the study authors noted. In the setting of suspected acute coronary syndrome, they said, female sex-specific biomarker thresholds have been shown to identify more women with myocardial injury.

“Sex-specific cut-offs are necessary for the diagnosis of perioperative myocardial injury to improve outcomes of women after CABG,” Gollmann-Tepeköylü’s group stressed. “Females above the threshold should undergo rapid further diagnosis to exclude [perioperative myocardial infarction] and if present, to reverse its cause. This might hopefully contribute to reducing the disparity in sex-associated outcomes after CABG.”

The present study, along with a recent post-hoc analysis of periprocedural myocardial infarctions by sex among people with stable coronary artery disease (CAD) in the ISCHEMIA trial, “support the concept that the biomarker threshold should be different by sex,” according to cardiac surgeon Mario Gaudino, MD, PhD, of Weill Cornell Medicine/NewYork-Presbyterian Hospital in New York City. It is “time to stop using data derived from a prevalently male population to women with CAD,” urged Gaudino, who was not part of Gollmann-Tepeköylü’s group.

Gaudino noted that he is currently leading the ROMA:Women and RECHARGE:Women trials underway assessing surgical and interventional revascularization strategies specifically for women.

For the present study, the authors retrospectively analyzed patient records from two centers — one in Austria and the other in Germany. They included the consecutive 3,687 people who underwent CABG for multivessel coronary artery disease from 2008 to 2021 and had serial postoperative hs-cTn and CK-MB measurements from various assays.

The exact surgical strategy for each person was left to the discretion of each operator.

A total of 82.6% of the participants were men and age 66.7 years on average. At baseline, women were generally older and sicker than the men, and had a significantly higher EuroSCORE II.

“Thus, despite efforts to adjust for these differences, it is possible that lower-level troponin elevation was associated with worse outcome in higher-risk patients and not necessarily only due to gender,” cautioned Donald Cutlip, MD, an interventional cardiologist at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.

He told MedPage Today in an email that there is also concern about “whether there is a causal relationship or confounding by other high risk features.”

“Nevertheless, the findings are provocative and require confirmation from other datasets for both percutaneous and surgical interventions,” he commented. “The results have potential implications for how we assess cardiac biomarkers, especially troponin thresholds, after cardiac procedures — both for clinical practice and clinical trial designs.”

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