Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing

• Baseline IL-6 levels were higher in young women compared to age-matched men.
• IL-6 levels increased significantly after both mental and physical stress.
• Men and women had similar IL-6 responses to both mental and physical stress.
• After stress, IL-6 levels remained higher in young women compared to young men.
• Sex differences in IL-6 persisted after accounting for risk factors.

ObjectivesYoung women have poorer prognosis after myocardial infarction (MI) and a higher rate of mental stress-induced ischemia compared with similarly aged men. A higher inflammatory status may help explain these sex differences.MethodsWe examined 98 patients (49 women and 49 men) age 18–59 years with recent MI (past 6 months). Women and men were matched for age, type of MI, and time since MI. Interleukin 6 (IL-6) concentrations were measured at baseline, after mental stress using a speech task, and after exercise/pharmacologic stress (60 and 90 min). Depressive symptoms were measured with the Beck Depression Inventory (BDI-II) and angiographic coronary artery disease (CAD) severity was quantified with the Gensini score. Single-photon emission computed tomography (SPECT) was used to obtain a computerized measurement of stress-induced ischemia (summed difference score, or SDS) and determine whether severity of stress-induced ischemia affects the inflammatory response to stress. Analysis was stratified by the median age of 50. Geometric mean concentrations of IL-6 were obtained from general linear regression models.ResultsIn both age groups, women had less angiographic CAD and a similar level of conventional risk factors compared with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women ⩽50 years of age compared to age-matched men (3.8 vs. 1.8 pg/mL, p = 0.001, across both conditions), while they were similar in women and men age >50 years (2.3 vs. 2.2 pg/mL, p = 0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women ⩽50 years than men at both 60 min (5.4 vs. 2.6 pg/mL, p = 0.002) and 90 min (5.9 vs. 3.4 pg/mL, p = 0.01). No significant difference was found between women and men >50 years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both mental and physical stress. Baseline IL-6 concentrations were not significantly related to inducible ischemia.ConclusionsAfter MI, young women aged 50 years or younger, compared with age-matched men, have remarkably higher concentrations of inflammation at baseline and after both mental and physical stress, with a similar inflammatory response to both stressors. Sustained concentrations of inflammation in young women, not their response to stress, may contribute to their adverse outcomes post-MI.