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

Abstract

Objectives Young 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. Methods We 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. Results In 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. Conclusions After 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.

Behavioral, emotional and neurobiological determinants of coronary heart disease risk in women

“…They also show an increase in negative emotions with non-psychological stressors, such as an inflammatory challenge with endotoxin, even though the inflammatory response is similar (Moieni et al, 2015). The similar physiological response to an inflammatory stimulus in women compared with men in this experimental study parallels the finding that young women with a previous history of MI show the same inflammatory response to mental stress as age-matched men; however, women exhibit double the level of interleukin-6 (IL-6) than men, both at baseline and at 90 min after the stress challenge (Rooks et al, 2016). Even in absence of CHD, women exhibit higher levels of C-reactive protein, a commonly studied inflammatory marker, compared with men of similar age, starting at age 16, potentially due to the onset of menarche (Ford et al, 2003; Wener et al, 2000; Woloshin and Schwartz, 2005).…”

“…Since these disturbances have been linked to ambulatory ischemia and MSIMI (Burg et al, 2014; Gullette et al, 1997a; Wei et al, 2014a), it is possible that repeated, cumulative distress in everyday life leads to a chronic form of microvascular diastolic dysfunction which is present at baseline and predicts MSIMI (Ersboll et al, 2014). All these potential vascular effects may be accentuated in young women given their higher baseline levels of inflammation (Rooks et al, 2016). Thus, the fact that vascular dysfunction is an important mechanism of MSIMI could explain a female predominance of this phenomenon.…”

“…Young women with severe medical illnesses may be more vulnerable to the development of depression. For example, young women with a recent MI have a higher level of inflammation than men of similar age or older patients (Rooks et al, 2016), which in turn may predispose them towards developing depression. The high prevalence of depression might also be explained by the fact that depression is a strong risk factor for CHD in young/middle aged women (as compared to men and older populations).…”

Sex Differences in Mental Stress‐Induced Myocardial Ischemia in Patients With Coronary Heart Disease

“…A recent study reported a greater increase in depressed mood and feelings of social disconnection in healthy young women compared to men after exposure to an inflammatory challenge with endotoxin, even though the inflammatory response was similar . Similarly, in a previous study, we found that women ≤50 years with a recent MI had a similar inflammatory response to stress than men, but the level of interleukin‐6 was 2 times higher in women than men before, during, and after the stress challenge . It is possible that the high absolute levels of inflammation reached during stressful events pose young women above a threshold of risk for abnormal emotional and vascular responses to stress.…”

Sex differences in cardiovascular disease – Impact on care and outcomes

“…Thus, it is possible that women exhibit enhanced microvascular dysregulation with mental stress due to their propensity to vasomotor reactivity 74 . Stress-induced vasoconstriction could be accentuated in young women given their higher baseline levels of inflammation 75 . Overall, these studies have uncovered vulnerability for adverse effects of emotional stress on cardiovascular function in women.…”