Different Factors Drive Heart Attack Risk in Young Women vs Young Men

Yuan Lu, ScD, MSc

New research from a case-control study comparing young patients with acute myocardial infarction to matched controls provides insight into sex-based differences in the impact of various risk factors on cardiovascular risk in younger patients.

Results of the study, which leveraged data from the VIRGO study and NHANES, provide insight into a group of 7 risk factors identified by investigators, including diabetes, depression, hypertension or high blood pressure, current smoking, family history of AMI, low household income, and high cholesterol, that had stronger associations with increased risk of acute myocardial infarction in women compared with men.

“Young women with AMI are an unusual or extreme phenotype on account of their age,” said lead investigator Yuan Lu, ScD, MSc, an assistant professor at Yale School of Medicine, in a statement from Yale University. “In the past, we found that young women, but not older women, have a twice higher risk of dying after an AMI than similarly aged men. In this new study, we now identified significant differences in risk factor profiles and risk factor associations with AMI by sex.”

Despite representing a significant burden on mortality risk and long-term quality of life, most cardiologists and clinicians practicing cardiology would agree a dearth of information exists related to acute myocardial infarction in younger patients, particularly young women. Citing this limited knowledge base, investigators conducted the current study with the intent of providing insight into the sex-specific associations of demographic, clinical, and psychosocial risk factors with first acute myocardial infarction among adults younger than 55 years, overall, and by subtype.

Designed as a matched case-control study, investigators used patient data obtained from the VIRGO study to represent a population with acute myocardial infarction and matched these patients based on age, sex, and racial/ethnic background from controls within the NHANES population. Pulling a random sample of patients from the study, which was the largest prospective observational study of young women and men with acute myocardial infarction in the US, the VIRGO study provided investigators with data related to a cohort of 2985 patients aged 18-55 years from 103 medical centers across the US for inclusion in the current analyses.

Ultimately, investigators identified 2264 patients with a first acute myocardial infarction from the VIRGO study and 2264 age-, sex-, and race and ethnicity-matched controls from NHANES for inclusion in their study. These patients had a median age of 48 (IQR, 44-52) years, 68.9% were women, and 75.3% were non-Hispanic White individuals. Among those from the VIRGO study, 82.2% had type 1 acute myocardial infarction, 3.8% had type 2 acute myocardial infarction, and 14.0% had other subtypes. Investigators pointed out 3.4% of patients with acute myocardial infarction had a history of cancer.

The primary outcomes of interest for the investigators’ analyses were the odds ratios (ORs) and population attributable fractions (PAFs) for first acute myocardial infarction associated with demographic clinical, and psychosocial risk factors. Adjusted analyses used conditional logistic regression to quantify associations of various risk factors with acute myocardial infarction, with adjustment for all covariates that were considered significant in univariable analysis.

Univariable analyses revealed 13 risk factors significantly associated with higher odds of acute myocardial infarction among younger women, with 9 risk factors associated with higher odds among men. investigators pointed out significant sex interactions were observed for diabetes, depression, hypertension, current smoking, and family history of diabetes, with these risk factors having stronger associations in women compared with men.

In adjusted analyses, investigators identified a group of 7 risk factors that accounted for the majority of total risk of acute myocardial infarction in women and men. These 7 factors were diabetes (women: OR, 3.59 [95% CI, 2.72-4.74]); men: OR, 1.76 [95% CI, 1.19-2.60]), depression (women: OR, 3.09 [95% CI, 2.37-4.04]; men: OR, 1.77 [95% CI, 1.15- 2.73]), hypertension (women: OR, 2.87 [95% CI, 2.31-3.57]; men: OR, 2.19 [95% CI, 1.65-2.90]), current smoking (women: OR, 3.28 [95% CI, 2.65-4.07]; men: OR, 3.28 [95% CI, 2.65-4.07]), family history of premature myocardial infarction (women: OR, 1.48 [95% CI, 1.17-1.88]; men: OR, 2.42 [95% CI, 1.71-3.41]), low household income (women: OR, 1.79 [95% CI, 1.28-2.50]; men: OR, 1.35 [95% CI, 0.82-2.23]), and hypercholesterolemia (women: OR, 1.02 [95% CI, 0.81-1.29]; men: OR, 2.16 [95% CI, 1.49-3.15]).

Assessments of PAFs for each risk factor of interest revealed the attributable fractions for diabetes (26.8% vs 9.9%), depression (25.5 vs 8.7%), hypertension (40.5% vs 31.8%), and current smoking (38.9% vs 35.1%) were greater among women compared with their male counterparts. In contrast, PAFs of hypercholesterolemia (49.1% vs 1.5%) and family history of premature myocardial infarction (16.8% vs 9.6%) were greater among men compared to their female counterparts.

Additionally, results suggested current smoking, hypertension, diabetes, and depression had a combined PAF of 80.2% compared with 63.2% in men. Investigators noted the 7 factors identified in multivariable analyses accounted for 83.9% of the total risk of acute myocardial infarction in women and 85.1% of the total risk of acute myocardial infarction in men. Further analysis indicated risk factor profiles carried by subtype, with traditional cardiovascular risk factors aging a higher prevalence and stronger odds ratios for type 1 acute myocardial infarction compared with other subtypes.

“This study speaks to the importance of specifically studying young women suffering heart attacks, a group that has largely been neglected in many studies and yet is about as large as the number of young women diagnosed with breast cancer,” said senior investigator Harlan Krumholz, MD, SM, the Harold H. Hines Jr. Professor of Medicine at Yale and director of the Center for Outcomes Research and Evaluation, in the aforementioned statement.

This study, “Sex-Specific Risk Factors Associated With First Acute Myocardial Infarction in Young Adults,” was published in JAMA Network Open.