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Original Investigation |

Lifelong Gender Gap in Risk of Incident Myocardial Infarction The Tromsø Study ONLINE FIRST

Grethe Albrektsen, PhD1; Ivar Heuch, PhD2; Maja-Lisa Løchen, MD, PhD3; Dag Steinar Thelle, MD, PhD4,5; Tom Wilsgaard, PhD3; Inger Njølstad, MD, PhD3; Kaare Harald Bønaa, MD, PhD1,3,6
[+] Author Affiliations
1Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
2Department of Mathematics, University of Bergen, Norway
3Department of Community Medicine, Faculty of Health Sciences, UiT–The Arctic University of Norway, Tromsø, Norway
4Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway
5Section for Epidemiology and Social Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
6Clinic for Heart Disease, St Olavs University Hospital, Trondheim, Norway
JAMA Intern Med. Published online September 12, 2016. doi:10.1001/jamainternmed.2016.5451
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Importance  It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce.

Objective  To quantify the difference in risk of incident myocardial infarction (MI) between men and women.

Design, Setting and Participants  Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015.

Exposures  Sex, age, birth cohort, serum lipid levels, blood pressure, lifestyle factors, diabetes.

Main Outcomes and Measures  Incident MI.

Results  A total of 2793 individuals (886 women) received a diagnosis of MI during follow-up in the period 1979 through 2012. The IR increased with age in both sexes, with lower rates for women until age 95 years. Adjusted for age and birth cohort, the overall IRR for men vs women was 2.72 (95% CI, 2.50-2.96). Adjustment for high-density lipoprotein cholesterol and total cholesterol levels had the strongest impact on the risk estimate for sex, followed by diastolic blood pressure and smoking. However, the sex difference remained substantial even after adjustment for these factors (IRR, 2.07; 95% CI, 1.89-2.26). Men had higher risk throughout life, but the IRRs decreased with age (3.64 [95% CI, 2.85-4.65], 2.00 [95% CI, 1.76-2.28], and 1.66 [95% CI, 1.42-1.95] for age groups 35-54, 55-74, and 75-94 years, respectively). Adjustment for systolic blood pressure, diabetes, body mass index, and physical activity had no notable impact.

Conclusions and Relevance  The observed sex contrast in risk of MI cannot be explained by differences in established CHD risk factors. The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men. The minor changes in IRs when moving from premenopausal to postmenopausal age in women make it unlikely that changes in female hormone levels influence the risk of MI.

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Age-Incidence Curves for Incident Myocardial Infarction (MI) in Men and Women

A, Crude incidence rates increase with age for both sexes rather slowly until the age of 65 to 69 years, then more rapidly up to age 95 years. B, Predicted age-incidence rates, modeled as a fourth-order polynomial in Poisson regression analysis of person-years at risk, fit crude (observed) age-incidence curves well. The incidence rate ratio (IRR) of MI for men vs women decreased with age but persisted throughout life. C, Sex heterogeneity in risk of MI (IRR) remains substantial in young and old persons after adjustment for birth cohort, HDL-C in percent of total cholesterol, diastolic blood pressure, and daily smoking (incidence rates shown for reference categories of adjustment factors).

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