Non-traditional risk factors for myocardial infarction in adults under forty: A systematic review of emerging trends

doi:10.4330/wjc.v18.i2.116172

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World Journal of Cardiology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Systematic Reviews

World J Cardiol. Feb 26, 2026; 18(2): 116172
Published online Feb 26, 2026. doi: 10.4330/wjc.v18.i2.116172

Non-traditional risk factors for myocardial infarction in adults under forty: A systematic review of emerging trends

Tirath Patel, Muhammad Farhan, Nehal K Bhatt, Hewaz A Fatah, Joel J Peniel, Ved V Kaulgud, Tisimol Mathew, Aashita M Bapat, Waleed SS Harazeen, Abdullatif N Alatta, Ayoola Awosika

Tirath Patel, Department of Medicine, Trinity Medical Sciences University School of Medicine, Kingstown VC0100, Saint George, Saint Vincent and the Grenadines

Muhammad Farhan, Internal Medicine, Ajman University, Ajman 6263, United Arab Emirates

Nehal K Bhatt, Department of Medicine, Pramukhswami Medical College, Gujarat 380001, India

Hewaz A Fatah, Internal Medicine, Turaq Primary Healthcare Centre, General Directorate of Health, Erbil 44001, Arbīl, Iraq

Joel J Peniel, Internal Medicine, Tbilisi State Medical University, Tbilisi 0144, Georgia

Ved V Kaulgud, Aashita M Bapat, Internal Medicine, Hinduhrudaysamrat Balasaheb Thackrey Medical College, Mumbai 400005, Mahārāshtra, India

Tisimol Mathew, Internal Medicine, Davao Medical School Foundation, Davao 8016, Philippines

Waleed SS Harazeen, Abdullatif N Alatta, Internal Medicine, Ajman University, College of Medicine, Ajman 6263, United Arab Emirates

Ayoola Awosika, Department of Family Medicine, University of Illinois College of Medicine Peoria, Bloomington, IL 61601, United States

Author contributions: Patel T, Farhan M, Mathew T, and Awosika A were responsible for conceptualization; Patel T and Farhan M designed the work; Patel T and Awosika A undertook data acquisition and conducted data analysis; Farhan M, Kaulgud VV, and Bapat AM participated in article screening; Bhatt NK carried out literature review, data extraction and discussion development; Fatah HA and Harazeen WSS performed quality assessment; Fatah HA refined methodology; Peniel JJ interpreted data and reviewed the manuscript, conducted risk-of-bias assessment, data synthesis and wrote the results section; Kaulgud VV managed references and prepared figures; Mathew T wrote and reviewed the introduction and discussion sections; Bapat AM conducted formal analysis and contributed to the first draft; Harazeen WSS contributed to the original draft and did review and editing; Alatta AN prepared tables, participated in methodology work and discussion development; Patel T, Bapat AM, Awosika A, and Harazeen WSS contributed to writing the first draft; and all authors thoroughly reviewed and endorsed the final manuscript.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Ayoola Awosika, MD, Department of Family Medicine, University of Illinois College of Medicine Peoria, 1 Illini Drive, Bloomington, IL 61601, United States. ayoolaawosika@yahoo.com

Received: November 4, 2025
Revised: November 14, 2025
Accepted: January 4, 2026
Published online: February 26, 2026
Processing time: 97 Days and 2.4 Hours

Abstract

BACKGROUND

Myocardial infarction (MI) incidence is increasing in adults aged < 40 years, however, as many as 25% may occur with no traditional risk factors.

AIM

To look at non-traditional risk factors for early onset MI.

METHODS

Based on the guidance of PRISMA-2020, search of PubMed, EMBASE, Web of Science, Scopus and Cochrane Central Register of Controlled Trials between April 2015 and April 2020 for observational studies focusing on the association between non-traditional risk factors and MI in adults aged 18-40 years. Two reviewers independently screened studies, extracted data and checked quality using Newcastle-Ottawa Scale or Agency for Healthcare Research and Quality checklist. The protocol was registered in PROSPERO, No. CRD420251061098.

RESULTS

Thirteen studies (7 cohort, 4 case-control, 2 cross-sectional) from 11 countries met inclusion criteria with a sample size ranging from 154 participants in a pilot case-control study to 5.7 million people in a United States National Inpatient Sample analysis. Psychosocial factors showed consistent associations: Depression showed an MI risk 1.6-3.1-fold higher and being unpartnered was associated with a post-MI readmission risk that was 28%-31% higher. Autoimmune conditions had the greatest associations, with human immunodeficiency virus infection quadrupling odds of MI (4.06), and the risk of systemic lupus erythematosus doubling (2.12). Obstructive sleep apnea increased major adverse cardiovascular events by almost four times (hazard ratio = 3.87). Adhering to the Mediterranean diet was protective (odds ratio = 0.55). Accelerated biological aging (shortening of telomeres) separated young patients with MI from controls. Traditional risk factors did not account for up to 30% of MI cases in each of the cohorts. Most studies were of moderate to high quality, although causes of heterogeneity in design and age stratification of participants mixtures limited causality inference.

CONCLUSION

Non-traditional psychosocial, autoimmune, inflammatory, and lifestyle factors play an important role in the risk of MI in young adults. Integrating these factors into risk prediction models could improve the early identification of high-risk individuals and target prevention strategies for this vulnerable population.

Keywords: Acute myocardial infarction; Coronary artery disease; ST-elevation myocardial infarction; Young adult

Core Tip: Non-traditional risk factors such as psychosocial stressors, autoimmune disorders, biological aging and specific lifestyle and environmental exposures play a significant role in myocardial infarction risk and outcome among individuals aged < 40 years. Psychosocial factors like depression, low socioeconomic status, and unpartnered status were significantly associated with adverse events, especially among young women. Autoimmune diseases and inflammation indicators, as well as sleep disorders and unhealthy lifestyle patterns, additionally improved the risk.