Childhood Stress, Trauma Linked to Worse Outcomes After Early MI

Among people who experience an MI before age 60, childhood or adolescent trauma is a common denominator that can double the risk of death, stroke, and other adverse events, according to findings from the Myocardial Infarction and Mental Stress 2 (MIMS2) study.

Primary investigator Zakaria Almuwaqqat, MD, MPH (Emory University School of Medicine, Atlanta, GA), told TCTMD that epidemiologists have suspected this association for a long time.

“Previous studies indicated that patients with a high burden of early trauma are at a higher risk for cardiometabolic risk factors,” he said. “However, in this study, we have witnessed that among a high-risk group of young and middle-aged MI survivors, this association was independent of known cardiovascular risk factors and is partly mediated through inflammation.”

Almuwaqqat presented the findings in a moderated poster session at the virtual American Heart Association 2020 Scientific Sessions on November 13, 2020, and they were simultaneously published online in JAMA Cardiology.

The study of 300 patients with a documented history of MI in the previous 8 months assessed trauma that occurred before age 18 using the 27-item Early Trauma Inventory-Self Report Short Form (ETI-SR-SF). Four components make up the score: general trauma, emotional abuse, sexual abuse, and physical abuse.

“Some of the common exposures are witnessing a natural disaster, violence, or murder; having a serious illness or witnessing a serious illness in the family; or having alcoholic parents,” Almuwaqqat said.

Moderator Sadiya S. Khan, MD, MSc (Northwestern University Feinberg School of Medicine, Chicago, IL), said the study “helps to frame how we think about risk assessment and prevention in high-risk individuals who we've generally thought about in terms of [traditional] risk factors.”

Dose-Dependent Relationship

The MIMS2 investigators set the threshold for self-reported early trauma on the ETI-SR-SF at 7. Patients with scores of 7 or higher were more likely than those with lower scores to be Black or African American and to have a more adverse socioeconomic, psychosocial, and cardiometabolic profile. Higher scores also were more closely related to higher baseline levels of interleukin-6 and C-reactive protein (CRP), independent of demographic and clinical risk factors. Higher scores also were associated with a greater likelihood of symptoms of depression and posttraumatic stress disorder.

Over 3-year follow-up, 26% of patients with an ETI-SR-SF of 7 or higher experienced the study endpoint (composite of CV death, MI, stroke, or hospitalization for heart failure) compared with 13% of those with scores below 7 (P = 0.004). After adjustment for demographic and CV risk factors, each 4-point increase in the ETI-SR-SF score was associated with a 20% increase in risk of the primary endpoint. Additionally, patients in the highest exposure quartile (scores > 11) had more than fourfold increased risk compared with those in the lowest quartile (scores 0-2). In multivariable analysis, the results remained consistent for the primary endpoint. However, there was no longer a statistical significance when baseline CRP was added.

Following the presentation, Khan noted the timeliness of the findings given the concern about the long-term impact of the stress of the global COVID-19 pandemic on young people. She asked Almuwaqqat how childhood or adolescent experiences might ultimately lead to adverse CV outcomes much later in life.

Almuwaqqat said there is likely a multipathway response that involves a combination of lifestyle factors, psychosocial factors, and early-life trauma that alters brain response. To TCTMD, he said it is clear that early-life trauma is an underrecognized, yet prevalent, public health hazard.

“Patients with a higher burden of early-life trauma might benefit from focused cardiovascular prevention efforts to improve health outcomes throughout the life span,” Almuwaqqat said. “Further studies should investigate the potential benefits of recognizing and treating early-life adversity and stress, particularly among high-risk patients such as MI survivors and those with premature CAD.”