Sex Differences in Inflammatory Markers and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) Study

Abstract

Background: Young women (≤55 years of age) with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. Elevated inflammatory markers are associated with an increased risk of cardiovascular outcomes after AMI, but little is known about whether young women have higher inflammatory levels after AMI compared with young men.

Methods and results: We assessed sex differences in post-AMI inflammatory markers and whether such differences account for sex differences in 12-month health status, using data from 2219 adults with AMI, 18 to 55 years of age, in the United States. Inflammatory markers including high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 were measured 1 month after AMI. Overall, women had higher levels of hsCRP and lipoprotein-associated phospholipase A2 after AMI compared with men, and this remained statistically significant after multivariable adjustment. Regression analyses showed that elevated 1-month hsCRP was associated with poor health status (symptom, function, and quality of life) at 12 months. However, the association between hsCRP and health status became nonsignificant after adjustment for sociodemographics, comorbidities, and treatment factors. Half of these patients had residual inflammatory risk (hsCRP >3 mg/L) compared with a third who had residual cholesterol risk (Low-density lipoprotein cholesterol >100 mg/dL).

Conclusions: Young women with AMI had higher inflammatory levels compared with young men. Elevated 1-month hsCRP was associated with poor health status at 12 months after AMI, but this was attenuated after adjustment for patient characteristics. Targeted anti-inflammatory treatments are worthy of consideration for secondary prevention in these patients if ongoing trials of anti-inflammatory therapy prove effective.

Trial registration: ClinicalTrials.gov NCT00597922.

Keywords: C-reactive protein; biomarkers; inflammation; myocardial infarction; women.

Conflict of interest statement

Conflict of Interest Disclosures: Dr. Krumholz is a recipient of research agreements from Medtronic and from Johnson & Johnson (Janssen), through Yale University, to develop methods of clinical trial data sharing; is the recipient of a grant from the Food and Drug Administration and Medtronic to develop methods for post-market surveillance of medical devices; works under contract with the Centers for Medicare & Medicaid Services to develop and maintain performance measures; chairs a cardiac scientific advisory board for UnitedHealth; is a participant/participant representative of the IBM Watson Health Life Sciences Board; and is the founder of Hugo, a personal health information platform. Dr. Spertus is supported by grants from Gilead, Genentech, Lilly, Amorcyte, and EvaHeart, and has a patent for the Seattle Angina Questionnaire with royalties paid. He also owns the copyright to the SAQ. Dr. Ridker is listed as a co-inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes that have been licensed to Seimens and AstraZeneca, and has received investigator-initiated research funding from Novartis, Amgen, Pfizer, Kowa, AstraZeneca, and the National Institutes of Health.

© 2017 American Heart Association, Inc.

Figures

Figure 1. Flowchart of sample selection for post-AMI inflammatory analysis in VIRGO

Figure 2

Distributions of inflammatory markers at 1 month after discharge for AMI, by sex (men = blue, women = red). AMI= acute myocardial infarction; VIRGO = Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients; HsCRP = high-sensitivity C-reactive protein; Lp-PLA2 = lipoprotein-associated phospholipase A2.