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Sex-related differences in clinical outcomes among patients with myocardial infarction with nonobstructive coronary artery disease: A systematic review and meta-analysis

https://doi.org/10.1016/j.ijcard.2022.07.050Get rights and content

Highlights

  • The influence of sex on adverse events in MINOCA remains unclear.

  • Our meta-analysis of >28,000 MINOCA patients showed women had more MACE than men (10.1% vs. 9.1%).

  • The adverse events in women were driven only by higher incidence of stroke in women (3.5% vs. 2.2%, p < 0.05).

  • Diminishing influence of estrogen, hypercoagulability, and underprescribing in women are likely contributors to MACE.

Abstract

Background

Among patients who present with acute myocardial infarction (MI), 2–6% are found to have non-obstructive coronary arteries (NOCA). Patients with MINOCA are more commonly women and present at a younger age (51–59 years). The influence of sex on adverse event rates remains unclear.

Methods

PubMed, MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), EMBASE, EBSCO, Web of Science and CINAHL databases were searched for trials comparing gender differences in clinical outcomes among patients with MINOCA from inception through April 10, 2022. The primary endpoint of the study was composite major adverse clinical events (MACE) including all-cause mortality, non-fatal MI, stroke, and cardiovascular readmissions, and secondary endpoints were the individual components of the MACE.

Results

Seven studies with a total of 28,671 MINOCA patients were included (n = 11,249 men and n = 17,422 women) over a mean follow-up of 2 years. Women had more MACE than men (10.1% vs. 9.1%, OR 1.15, 1.04–1.23, I2 = 44.7%). Among secondary endpoints, only the incidence of stroke was higher in women (3.5% vs. 2.2%, OR 1.3, 1.01–1.68, I2 = 0%). All-cause mortality, non-fatal MI, and cardiovascular readmissions were not significantly different between the two groups.

Conclusions

We hypothesize that small vessel disease associated with MINOCA drives MACE in women and the diminishing influence of estrogen, hypercoagulability and underprescribing could contribute to the differences sex-related outcomes.

Introduction

Among patients who present with acute myocardial infarction (MI), 2–6% are found to have non-obstructive coronary arteries (NOCA). Patients with MINOCA are more commonly women and present at a younger age (51–59 years). The influence of sex on adverse event rates remains unclear [[1], [2], [3], [4], [5], [6], [7]].

Section snippets

Methods

We performed a systematic review and meta-analysis according to Cochrane Collaboration guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched for studies comparing sex-related differences in clinical outcomes among patients with MINOCA from inception through April 10, 2022, using the keywords “myocardial infarction with non-obstructive coronary artery disease”,

Results

After screening 612 potentially relevant clinical studies, seven clinical studies were included with a total of 28,671 MINOCA patients (n = 11,249 men and n = 17,422 women) over a mean follow-up of 2 years (Fig. 1) [[1], [2], [3], [4], [5], [6], [7]]. Women had more MACE than men (10.1% vs. 9.1%, OR 1.15, 1.04–1.23, I2 = 44.7% Fig. 2a). Among secondary endpoints, only the incidence of stroke was higher in women (3.5% vs. 2.2%, OR 1.3, 1.01–1.68, I2 = 0% Fig. 2b). All-cause mortality, non-fatal

Discussion

The epidemiology of ischemic heart disease from large-vessel atherosclerosis is well known but that of myocardial small vessel disease (SVD) is less well documented. The vascular anatomy of the heart and brain have similarities. The SVD of the heart involves the deep penetrating arterioles with a subendocardial plexus of microvessels and the brain involves the small subcortical cerebral arteries. Occlusion of any subcortical cerebral arteries in the brain may result in lacunar stroke syndrome.

Study Limitations

Our study has several limitations. First, the study population within the individual studies was heterogeneous (due to the broad definition of MINOCA [14] (Table 1)) with a variable follow-up (in-hospital visit to 3.8 years). Second, no patient-level data were available to differentiate between the etiologies of MINOCA.

Conclusions

In conclusion, our study suggests that women with MINOCA had worse clinical outcomes compared to men at up to 24 months of follow-up which were driven by an increased incidence of stroke. The diminishing influence of estrogen, hypercoagulability and underprescribing could contribute to the differences sex-related outcomes.

Authorship Statement.

All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Funding

None.

CRediT authorship contribution statement

Rahul Chaudhary: Conceptualization, Data curation, Formal analysis, Project administration, Writing – original draft. Michael Bashline: Conceptualization, Data curation, Formal analysis, Project administration, Writing – original draft. Enrico M. Novelli: Conceptualization, Supervision, Writing – review & editing. Kevin P. Bliden: Data curation, Formal analysis, Methodology, Writing – original draft. Udaya S. Tantry: Methodology, Project administration, Writing – review & editing. Oladipupo

Declaration of Competing Interest

Dr. Gurbel has received consulting fees and/or honoraria from Bayer, Otitopic, Janssen, UpToDate, Cleveland Clinic, Adeno, Wolters Kluwer Pharma, Web MD Med-scape, Baron and Budd, North American Thrombosis Forum, Innovative Sciences; institutional research grants from the Haemonetics, Janssen, Bayer, Instrumentation Laboratories, Amgen, Idorsia, Otitopic, Hikari Dx, Novartis, Precision Biologic, Nirmidas Biotech, and R-Pharma International; in addition, Dr. Gurbel has two patents, Detection of

Acknowledgement(s)

None.

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