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Study Calls for Sex-Specific Tactics to Reduce Rising Heart Attacks in Young Adults


These investigators wanted to better understand the reasons for the increased risk for acute myocardial infarctions among young women, who have the largest increase in hospitalization for heart attacks.

Researchers are calling for sex-specific strategies to address the risk of acute myocardial infarction (AMI) among both young women and men—that is, younger than 55 years—after their study found several factors, contributing up to 85% of the greater risk of first AMI, are modifiable. These strategies need to address both risk factor modification and prevention.

Their overall results also point out disparities in the risk profile, such that “significant differences in risk factor profiles and risk factor associations existed by sex and AMI subtype,” the authors wrote. The authors noted that they took up their investigation because first AMIs are being seen in more young people in the United States and women have the largest increase in this cardiac event. In addition, they wanted a better understanding of the risk factors among women vs men.

Findings were published online today in JAMA Network Open. The primary outcome was 2-fold: odds ratios (ORs) and population-attributable factors (PAF) for first AMI per demographic, clinical, and psychosocial risk factors.

Using 2008-2012 data from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) and the National Health and Nutrition Examination Survey, for their study (n = 2264) and control (n = 2264) populations, respectively, age, sex, race, and ethnicity were used to match the study participants. Most (68.9%) were women and non-Hispanic White (75.3%), and their median (IQR) age was 48 (44-52) years.

According to results, multivariable analysis showed 83.9% of the total AMI risk in women and 85.1% of that among men is due to 7 factors, with 4 of these having higher odds for women and 2 having higher odds for men:

  • Diabetes:
    • Women: 3.59 (95% CI, 2.72-4.74)
    • Men: 1.76 (95% CI, 1.19-2.60)
  • Depression:
    • Women: 3.09 (95% CI, 2.37-4.04)
    • Men: 1.77 (95% CI, 1.15-2.73)
  • Hypertension:
    • Women: 2.87 (95% CI, 2.31-3.57)
    • Men: 2.19 (95% CI, 1.65-2.90)
  • Low household income:
    • Women: 1.79 (95% CI, 1.28-2.50)
    • Men: 1.35 (95% CI, 0.82-2.23)
  • Family history of premature MI:
    • Women: 1.48 (95% CI, 1.17-1.88)
    • Men: 2.42 (95% CI, 1.71-3.41)
  • Hypercholsterolemia:
    • Women: 1.02 (95% CI, 0.81-1.29)
    • Men: 2.16 (95% CI, 1.49-3.15)

When considering their status as a current smoker, the increased risk was the same between men and women, at 2.28 times that of a nonsmoker (OR, 3.28; 95% CI, 2.65-4.07).

In addition, when looking at just women or just men, there were 13 and 9 risk factors, respectively, that had significant associations with higher odds of AMI.

Further, individual consideration of the risk factors showed that the PAFs varied between the sexes:

  • Diabetes: 26.8% for women vs 9.9% for me
  • Depression: 25.8% for women vs 8.7% for men
  • Hypertension: 40.5% for women vs 31.8% for men
  • Current smoker: 38.9% for women vs 35.1% for men
  • Hypercholesterolemia: 49.1% for men vs 1.5% for women
  • Family history of premature MI: 16.8% for men vs 9.6% for women

Combined, the PAH results equate to 80.2% of the higher AMI risk in women compared with 63.2% in men.

The AMI subtypes investigated were type 1, defined by the authors as AMI caused by plaque rupture, ulceration, fissuring, erosion or dissection with resulting thrombus; type 2, “condition other than coronary artery disease contributes to imbalance between myocardial oxygen supply or demand; type 4b, stent thrombosis; and unclassified. Overall, the most common AMI subtype was type 1 among 82.2%.

When focusing on women and Black patients, other types of AMI (type 2, type 4b, unclassified) were much more common vs type 1: 78.2% vs 67.0% and 19.1% vs 15.6%, respectively. However, diabetes, hypercholesterolemia, obesity, and being a current smoker were more common risk factors among those with type 1 AMI vs other types (P < .05).

In addition, diabetes, depression, hypertension, being a current smoker, family history of diabetes, and history of congestive heart failure were associated with greater risk of type 1 AMI in women vs men, whereas hypercholesterolemia had a stronger relationship with type 1 AMI in men.

One-third of the 800,000 persons hospitalized for AMI each year in the United States are younger than 55 years, the authors noted, but most previous studies in risk of AMI have not included control populations; have focused just on men, women, or older adults; and have relied on diagnosis code and self-reported data without confirmation.

“To the best of our knowledge, this is the largest study in the US that focused on young women and a comparable sample of similarly aged men,” they wrote, “and comprehensively evaluated the associations between a wide range of predisposing risk factors and incident AMI by sex.”

Their findings are important because they were seen among a large patient group and following evaluation of metabolic, familial, and social risk factors not previously comprehensively evaluated; they identify significant differences between men and women for AMI risk factors; and compared with previous studies, “provide new insights into the epidemiology of etiologically distinct classes of myocardial injury in young adults.”

To make progress in this space, the authors recommend more research on the role of familial risk factors that may contribute to AMI occurrence in young adults, on nontraditional sex-specific risk factor modification and prevention in young women (ie, psychological stressors and poverty), and on implementing evidence-based prevention guidelines in women.


Lu Y, Li S-X, Liu Y, et al. Specific risk factors associated with first acute myocardial infarction in young adults. JAMA Netw Open. Published online May 3, 2022. doi:10.1001/jamanetworkopen.2022.9953

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