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Objective Mental stress-induced myocardial ischemia (MSIMI), a transient myocardial ischemic response to mental stress, is associated with poorer outcomes among patients with coronary heart disease and is more likely to occur among women. However, predictors of MSIMI are not well explored. The current study investigated the association between experiences of everyday discrimination and MSIMI among patients with recent myocardial ischemia and contrasted the results with conventional stress-induced myocardial ischemia (CSIMI). We examined sex differences in associations. Methods We studied 295 post-MI patients (145 women, 150 men). Provocation of myocardial ischemia with mental stress (speech task) and conventional stress (exercise or pharmacologic) was assessed by myocardial perfusion imaging. Frequency of exposure to everyday discrimination was assessed via questionnaire using the Everyday Discrimination Scale (EDS). Results The mean age was 51 years in both women and men, and the EDS score ranged from 10 to 38 (mean [standard deviation] = 17 [6] years). After multivariable analysis, each standard deviation increase in the EDS score (more frequent exposure) was associated with an increased odds of MSIMI (odds ratio [OR] = 1.57 [1.10-2.23]). The EDS score was not associated with CSIMI (OR = 0.86 [0.64-1.17]). Women demonstrated a twofold increase (OR = 1.96 [1.13-3.38], p = .02) in the adjusted odds of MSIMI, with each standard deviation increase in the EDS score compared with a 1.4-fold increase (OR = 1.40 [0.80-2.44], p = .24) among men; however, interaction was not statistically significant. Conclusions Among post-MI patients, everyday discrimination was positively associated with occurrence of MSIMI, but not with CSIMI; associations were more pronounced among women.

Objective Mental stress-induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease (CAD). The link between an integrated measure of chronic psychosocial distress and mental stress-induced myocardial ischemia, and whether it differs by sex, has not been examined before. Methods We used latent class analysis to derive a composite measure of psychosocial distress integrating scales of depression, posttraumatic stress, anxiety, anger, hostility, and perceived stress in 665 individuals with stable CAD. Participants underwent myocardial perfusion imaging with mental stress and perfusion defects were quantified at rest (summed rest score), with mental stress (summed stress score), and their difference (summed difference score), the latter being an index of inducible ischemia. Results The M (SD) age was 63 (9) years, and 185 (28%) were women. Latent class analysis characterized the study sample into four distinct classes of incremental psychosocial distress. In women, class 4 (highest distress) had an adjusted 4.0-point higher summed rest score (95% confidence interval = 0.2-7.7) as compared with class 1 (lowest distress), whereas no difference was observed in men (-0.87 points, 95% confidence interval = -3.74 to 1.99, p = .04 for interaction). There was no association between the psychosocial distress latent variable and summed difference score in either women or men. Conclusions Among patients with CAD, a higher level of psychosocial distress is not associated with mental stress ischemia, but it is associated with more resting (fixed) perfusion abnormalities in women only, as well as with blunted hemodynamic response to mental stress in both men and women.

Mental stress-induced myocardial ischemia (MSIMI) is a common phenomenon in patients with coronary artery disease (CAD), but contemporary studies of its prognostic significance and its underlying pathophysiology are limited.We prospectively enrolled patients with confirmed CAD in the Mental Stress Ischemia Prognosis Study (MIPS) between 2011 and 2014. All patients underwent mental stress testing using a standardized public speaking task, and ischemia was detected by Tc-sestamibi myocardial perfusion imaging. Patients also underwent conventional stress testing for myocardial ischemia (CSIMI) using exercise or pharmacological stress testing. Furthermore, digital microvascular flow, endothelial function, arterial stiffness, and blood sample collections were performed before, during, and after mental stress. Two-year adverse clinical outcomes are being assessed.Six-hundred ninety-five patients completed baseline enrollment in the MIPS. Their mean (standard deviation) age was 62.9 (9.1) years, 72% were men, 30% were African American, and 32% had a history myocardial infarction. The prevalence of MSIMI and CSIMI is 16.1% and 34.7%, respectively. A total of 151 patients (22.9%) had only CSIMI, 28 (4.2%) had only MSIMI, and 78 (11.8%) had both MSIMI and CSIMI. Patients with ischemia had a lower ejection fraction and higher prevalence of previous coronary artery bypass grafting compared with those without inducible ischemia (p.050). The prevalence of obstructive CAD was not statistically different between patients with and without MSIMI (p = .426); in contrast, it was higher in patients with CSIMI (p.001).The MIPS data will provide useful information to assess the prognostic significance and underlying mechanisms of MSIMI.

OBJECTIVE: It is unclear whether mental stress-induced myocardial ischemia (MSIMI) is related to obstructive coronary artery disease (CAD). We examined this question and contrasted results with ischemia induced by conventional stress testing (CSIMI). Because women are more susceptible to ischemia without coronary obstruction than men, we examined sex differences. METHODS: We studied 276 patients 61 years and younger with recent myocardial infarction. CAD severity was quantified using the log-transformed Gensini Score (lnGS) and the Sullivan Stenosis Score. Patients underwent myocardial perfusion imaging with mental stress (public speaking) and conventional (exercise or pharmacological) stress testing. MSIMI and CSIMI were defined as a new or worsening perfusion defect. RESULTS: The prevalence of MSIMI was 15% in men and 20% in women. The median GS for patients with MSIMI was 65.0 in men and 28.5 in women. In logistic regression models adjusted for demographic and cardiovascular risk factors, CAD severity was associated with CSIMI in the full sample (odds ratio [OR] = 1.49, 95% [CI], 1.14–1.95, per 1-unit increase in lnGS), with no significant difference by sex. Although CAD severity was not associated with MSIMI in the entire sample, results differed by sex. CAD severity was associated with MSIMI among men (OR = 1.95, 95% CI, 1.13–3.36, per 1-unit increase in lnGS), but not among women (OR = 1.02, 95% CI, 0.74–1.42, p = .042 for interaction). Analysis using Sullivan Stenosis Score yielded similar results. CONCLUSIONS: Findings suggest that CAD severity is related to MSIMI in men but not women. MSIMI in women may therefore be driven by alternative mechanisms such as coronary microvascular disease.

OBJECTIVE: Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed to the role of behavioral factors like emotional stress on CAD risk. Brain areas involved in memory and the stress response, including medial prefrontal cortex, insula and parietal cortex, also have outputs to the peripheral cardiovascular system. The purpose of this study was to assess the effects of mental stress on brain and cardiac function in patients with CAD. METHODS: CAD patients (N=170) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography (SPECT) at rest and during a public speaking mental stress task. On another day they underwent imaging of the brain with [O-15] water positron emission tomography (PET) during mental stress (arithmetic and public speaking) and control conditions. RESULTS: Patients with mental stress-induced myocardial ischemia (MSI) showed increased activation with stress in anterior cingulate, inferior frontal gyrus, and parietal cortex (p

OBJECTIVE Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress. METHODS Retrospective analysis of 218 patients with stable CAD, including 110 on ACEI, was performed. 99m-Tc-sestamibi myocardial perfusion imaging was used to define ischemia during mental stress, induced by a standardized public speaking task, and during physical stress, induced by either exercise or adenosine. RESULTS Overall, 40 patients (18%) developed MSIMI and 80 patients (37%) developed ischemia during physical stress. MSIMI occurred less frequently in patients receiving ACEIs (13%) compared with those not on ACEIs (24%; p = .030, adjusted odds ratio = 0.42, 95% confidence interval = 0.19-0.91). In contrast, the frequency of myocardial ischemia during physical stress testing was similar in both groups (39% versus 35% in those on and not on ACEIs, respectively); adjusted odds ratio = 0.91, 95% confidence interval = 0.48-1.73). CONCLUSION In this retrospective study, patients using ACEI therapy displayed less than half the risk of developing ischemia during mental stress but not physical stress. This possible beneficial effect of ACEIs on MSIMI may be contributing to their salutary effects in CAD.

Objectives Psychological stress may play a role in metabolic syndrome. A consequence of metabolic syndrome is endothelial dysfunction, which is also influenced by psychological stress. We sought to compare the effect of consciously resting meditation (CRM), a sound based meditation, with a control intervention of health education (HE) on endothelial function in the setting of metabolic syndrome. Methods Sixty-eight black Americans with metabolic syndrome risk factors (age, 30-65 years) were randomized to either CRM (n = 33) or HE (n = 35); interventions were matched for frequency and duration of sessions and lasted 12 months. Endothelial function was assessed by brachial artery flow-mediated dilation at baseline and at 6 and 12 months. Arterial elasticity, metabolic risk factors, and psychosocial and behavioral variables were secondary end points. Results Although flow-mediated dilation improved in the CRM group for 12 months, this increase was not significantly higher than that in the HE group (p = .51 for the interaction between group and time). Non-endothelium-dependent dilation and arterial elasticity did not change in either group. Most metabolic syndrome risk factors showed beneficial trends in the CRM group only. A risk factor score counting the number of metabolic syndrome components decreased in the CRM group only (p = .049 for the interaction between treatment group and time). Conclusions Among black Americans with metabolic syndrome risk factors, CRM, did not improve endothelial function significantly more than a control intervention of HE. CRM resulted in favorable trends in metabolic syndrome risk factors, which were examined as secondary outcomes.

A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated in neuropsychiatric disorders and also moderates the association between early-life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma, and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis.A sample including 289 middle-aged male twin pairs was studied. Subclinical atherosclerosis was assessed by brachial flow-mediated dilation (FMD) using ultrasound. Childhood trauma, before age 18 years, was measured with the Early Trauma Inventory and included physical, emotional, and sexual abuse as well as general trauma. Generalized estimating equation models were used to test the main and interactive effects of the MAOA genotype and each domain of childhood trauma on FMD, adjusting for known risk factors.General trauma was the most prevalent childhood trauma (28.4%), followed by physical abuse (25.0%), emotional abuse (19.4%), and sexual abuse (11.6%). MAOA genotype was not associated with any domain of childhood trauma. There was no significant evidence for a main effect for the MAOA genotype (β = .02, p = .82) or childhood trauma (.005β.10, p.54) FMD. However, a significant interaction was observed between MAOA genotype and physical (β interaction = .37, p = .026) or emotional abuse (β interaction = .43, p = .025) on subclinical atherosclerosis.Childhood trauma modulates the impact of MAOA variant on subclinical atherosclerosis, independent of traditional cardiovascular risk factors.

To assess whether genetic variants involved in inflammation play a role in the sex difference in depression. Depression is, in part, genetically determined and inflammation has been implicated. Women are twice as likely to develop depression as men.We examined the association, separately in men and women, between seven single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and 12 SNPs in the leukotriene A4 hydrolase (LTA4H) gene and depression in 1368 white subjects (30.4% female) referred for cardiovascular evaluation. Depression was defined as a score ofor=10 in the Patient Health Questionnaire 9. Single marker analysis was assessed by the chi(2) test. Haplotype-specific associations were performed, using likelihood ratio tests. Empirical significance levels were determined by permutation tests.Depressed individuals, comprising 14.5% of the total, were more likely to be female, current smokers, have a history of diabetes and myocardial infarction. None of the SNPs in the ALOX5AP gene, either singly or in combination, was associated with depression. The 12 SNPs in the LTA4H gene were not individually associated with depression. However, a six-SNP haplotype in LTA4H gene, named HapE, showed a significant protective effect on depression in women, but not in men, after correcting for cardiovascular effects. The interaction between HapE and sex on depression was statistically significant.This study provides the first evidence for a sex-specific association of a novel haplotype in the LTA4H gene on depression. Although replication is needed, our study suggests that genetic variations may underlie sex differences in depression.