Gender difference in MI risk cannot be explained by established CHD risk factors

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

Literature - Albrektsen G et al., JAMA Intern Med 2016

Albrektsen G, Heuch I, Løchen M-L, et al.
JAMA Intern Med 2016;published online ahead of print


CVD is more frequent in men than in women, but it is not clear whether this gender gap is due to differences in the levels of known risk factors, or not [1]. It has been hypothesised that the lower risk of CHD in premenopausal women is associated with a protective effect of female hormones, but this hypothesis has been debated [2]. Other possible explanations include gender heterogeneity in insulin resistance mechanisms, favourable LDL-C characteristics in women, and differences in aging processes influencing arterial stiffness [3].
In this large, population-based, prospective Norwegian study, the risk difference of incident MI between men and women was evaluated and it was assessed to what extent such a gender difference can be explained by different levels of CHD risk factors.

Main results

  • Incidence rate ratios (IRR, relative risk) for men vs women, adjusted for age were for 35-54 years:  6.78; 95% CI: 5.37-8.56, 55-74 years: 2.73; 95% CI: 2.42-3.09 and 75-94 years: 1.83; 95% CI: 1.59-2.11.
  • The RR of MI for men vs women, adjusted for age and birth cohort, was 2.72; 95% CI: 2.50-2.96.
  • The factors with the strongest impact on the association with gender, expressed as change in regression coefficient, were: -19.0% for HDL-C, 14.2% for total cholesterol (TC), -17.1% for the ratio between HDL-C and TC, -5.9% for DBP, and -5.6% for daily smoking.
  • The contrast in risk between sexes remained substantial (IRR: 2.07; 95% CI: 1.89-2.26; regression coefficient reduced by 27.3%) after adjustment for factors that changed the regression coefficient for gender by at least 5% in a model adjusted for all risk factors.
  • The adjusted risk curves were close to parallel before the age of 45-50 years and after the age of 70 years, but the distance between the curves was considerably smaller among the oldest.
  • In women, no sudden changes in risk were seen when moving from premenopausal to postmenopausal ages.
  • The sex difference in MI risk diminished with age but persisted throughout life. Adjusted IRRs for men vs women by age groups: 35-54 years: 3.64; 95% CI: 2.85-4.65, 55-74 years: 2.00; 95% CI: 1.76-2.28 and 75-94 years: 1.66; 95% CI: 1.42-1.95.


Compared with women, men have approximately twice the risk of MI. This difference cannot be explained by established CHD risk factors, it persists throughout life but declines with age. It seems unlikely that changes in female hormone levels influence MI risk. These data provide a better understanding of the gender gap in MI risk, which may be important for the prevention and treatment of CHD.

Find this article online at JAMA Internal Medicine


1. Stock EO, Redberg R. Cardiovascular disease in women. Curr Probl Cardiol. 2012;37(11):450-526.
2. Barrett-Connor E. Sex differences in coronary heart disease: why are women so superior? The 1995 Ancel Keys lecture. Circulation. 1997;95(1):252-264.
3. Anand SS, Islam S, Rosengren A, et al; INTERHEART Investigators. Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur Heart J. 2008;29(7):932-940.

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