Sex-Specific Risk Factors Associated With First Acute Myocardial Infarction in Young Adults

This case-control study assesses 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 infarction subtype.


eMethods.
Methods to calculate population attributable fraction for individual risk factors.
Population attributable fraction (PAF) quantifies the fraction of AMI cases in the population that were attributable to an exposure to one or several risk factors. 1 In this study, provided the disease outcome AMI is relatively rare, PAF can be derived by substituting relative risk with a odds ratio estimated from a conditional logistic regression model. A clustered sandwich formula is used in the variance and confidence interval calculation.
PAF for a simple dichotomous exposure and disease, and no adjustment for confounding, was estimated using formula (1).
Where is the proportion of cases exposed to risk factor, is the unadjusted odds ratio, estimated by the univarible conditional logistic regression model PAF adjusted for confounding was calculated using formula (2).
Where is the proportion of cases exposed to risk factor, is the adjusted odds ratio, estimated by the multivarible conditional logistic regression model PAF for multiple risk factors was calculated using formula (3).
Where n is the number of the multiple risk factors eTable 1. AMI classification by the third global definition of MI.

Risk factor Ascertainment in VIRGO Ascertainment in NHANES Definition of variables used in analysis Marital status
In-person interview: Which best describes your current marital status?
In-person interview: Please describe your current marital status.
Marital status is classified as married/ living with partners vs. others (widowed, divorced, or separated; and never married).

Highest education level
In-person interview: What is the highest level of education you have completed?
In-person interview: What is the highest grade or level of school you have completed or the highest degree you have received?
Highest education level is classified as less than high school, high school, greater than high school.

Household income
In-person interview: What is your total household income (including those with whom you live, such as your spouse)?
In-person interview: Please describe your total household income (reported as a range value in dollars) Annual household income is classified as <10,000, 10,000-99,999, and ≥100,000.

Health insurance
In

Hypertension
In-person interview: • Has a doctor or other health professional ever told you that you have high blood pressure (excluding when you were pregnant)? • Have you ever taken medicine for high blood pressure? • Are you currently taking medicine for high blood pressure?
In-person interview: • Have you ever been told by a doctor or other health professional that you had hypertension, also called high blood pressure? • Because of your high blood pressure/hypertension, have you ever been told to take prescribed medicine? • Are you currenly taking prescribed medicine for high blood pressure Hypertension is defined based on self-reported previous diagnosis of hypertension or currently on antihypertensive medication.

Diabetes
In-person interview: • Have you ever been told that you have diabetes (excluding when you were pregnant)?
Medical chart abstraction: • Treatment of diabetes mellitus (check all that apply): None; diet; insulin; oral antidiabetics • HbA1c (%) in the most recent in past 3 months In-person interview: • Other than during pregnancy, have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes? • Are you now taking diabetic pills to lower your blood sugar? These are sometimes called oral agents or oral hypoglycemic agents. • Are you now taking insulin?
Diabetes is defined based on previous physician diagnosis, or HbA1c ≥ 6.5%, or currently on antidiabetic medication.
Lab measurement: All participants ages 12 and older are given the option of a HbA1C% test during their physical examination Hypercholesterolemia In-person interview: • Has a doctor or other health professional ever told you that you have high cholesterol or abnormal levels of fats in your blood? • Are you currently taking medicine for high cholesterol?
Medical chart abstraction: • Lipids in the most recent in past 12 months In-person interview: • Have you ever been told by a doctor or other health professional that your blood cholesterol level was high? • To lower your blood cholesterol, have you ever been told by a doctor or other health professional to take prescribed medicine? • Are you now following this advice to take prescribed medicine? Lab measurement: All participants ages 12 and older are given the option of a lipid test during their physical examination.
Hypercholesterolemia is defined based on previous physician diagnosis, or TC ≥200 mg/dL, or LDL-C ≥130 mg/dL, or HDL-C <40 mg/dL, or currently on lipidlowering medication.

Obesity
Medical chart abstraction: Height and weight are measured during the index AMI admission for all patients.
Physical examination: Standing height is measured in participants ages 2 and older and weight is measured in participants at all ages.
We calculated body-mass index as weight in kilograms divided by the square of height in meters and obesity was defined as body mass index ≥ 30 kg/m 2 .

Current smokers
In-person interview: • Which of the following best describes your current cigarette smoking status? • In the past 30 days, how many cigarettes did you smoke each day, on average? In-person interview: • Behavioral Risk Factor Surveillance Survey (BRFSS) physical activity instrument. • Patients were asked if they participated in moderate or vigorous physical activity during the past 30 days. If they answered yes to either question, they were then asked the duration Physical activity is classified into three levels: recommended (150 min or more of moderate physical activity or 75 min or more of vigorous physical activity per week), insufficient (between 10-149 min per week of moderate yes to either question, they were then asked the duration and frequency of their participation in physical activity for an average week. and frequency of their participation in physical activity for an average week. physical activity or between 10-74 min per week of vigorous physical activity), or inactive (no participation or fewer than 10 min of moderate or vigorous physical activity per week). History of congestive heart failure Medical chart abstraction: history of congestive heart failure was extracted from medical record at the index AMI admission for all patients.
In-person interview: Has a doctor or other health professional ever told you that you had congestive heart failure?
History of congestive heart failure is defined based on self-reported previous physician diagnosis of congestive heart failure Family history of premature MI In-person interview: Including living and deceased, were any of your close biological that is, blood relatives including grandparents, father, mother, sisters or brothers, ever told by a health professional that they had a heart attack or angina before the age of 50?
Family history of premature MI is defined as any of the participants' blood relatives ever had a heart attack before the age of 50.

Family history of diabetes
In-person interview: Do any blood relatives in your immediate family have diabetes?
In-person interview: Including living and deceased, were any of your biological relatives, that is, blood relatives, including grandparents, parents, brothers, and sisters, ever told by a health professional that they had diabetes?
Family history of diabetes is defined as any of the participants' blood relatives ever had diabetes.

Depression
In-person interview: Symptoms of depression that patients experienced in the past 2 weeks were assessed with the 9-item version of the Patient Health Questionnaire (PHQ-9) In-person interview: Symptoms of depression that patients experienced in the past 2 weeks were assessed with the 9-item version of the Patient Health Questionnaire (PHQ-9) Depressive symptom is defined as PHQ-9 score ≥ 10.