Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women's proclivity toward ischemia because of microcirculatory abnormalities.

Mental stress—induced myocardial ischemia (MSIMI) has been associated with adverse prognosis in patients with coronary artery disease (CAD), but whether this is a uniform finding across different studies has not been described. We conducted a systematic review and meta-analysis of prospective studies examining the association between MSIMI and adverse outcome events in patients with stable CAD. We searched PubMed, EMBASE, Web of Science, and PsycINFO databases for English language prospective studies of patients with CAD who underwent standardized mental stress testing to determine presence of MSIMI and were followed up for subsequent cardiac events or total mortality. Our outcomes of interest were CAD recurrence, CAD mortality, or total mortality. A summary effect estimate was derived using a fixed-effects meta-analysis model. Only 5 studies, each with a sample size of <200 patients and fewer than 50 outcome events, met the inclusion criteria. The pooled samples comprised 555 patients with CAD (85% male) and 117 events with a range of follow-up from 35 days to 8.8 years. Pooled analysis showed that MSIMI was associated with a twofold increased risk of a combined end point of cardiac events or total mortality (relative risk 2.24, 95% confidence interval 1.59 to 3.15). No heterogeneity was detected among the studies (Q = 0.39, I2 = 0.0%, p = 0.98). In conclusion, although few selected studies have examined the association between MSIMI and adverse events in patients with CAD, all existing investigations point to approximately a doubling of risk. Whether this increased risk is generalizable to the CAD population at large and varies in patient subgroups warrant further investigation.

BackgroundMental stress–induced myocardial ischemia (MSIMI) is associated with adverse prognosis in patients with coronary artery disease (CAD), yet the mechanisms underlying this phenomenon remain unclear. We hypothesized that compared with exercise/pharmacological stress–induced myocardial ischemia (PSIMI) that is secondary to the atherosclerotic burden of CAD, MSIMI is primarily due to vasomotor changes.Methods and ResultsPatients with angiographically documented CAD underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and following both mental and physical stress testing, performed on separate days. The severity and extent of CAD were quantified using the Gensini and Sullivan scores. Peripheral arterial tonometry (Itamar Inc) was used to assess the digital microvascular tone during mental stress as a ratio of pulse wave amplitude during speech compared with baseline. Measurements were made in a discovery sample (n=225) and verified in a replication sample (n=159). In the pooled (n=384) sample, CAD severity and extent scores were not significantly different between those with and without MSIMI, whereas they were greater in those with compared with those without PSIMI (P<0.04 for all). The peripheral arterial tonometry ratio was lower in those with compared with those without MSIMI (0.55±0.36 versus 0.76±0.52, P=0.009). In a multivariable analysis, the peripheral arterial tonometry ratio was the only independent predictor of MSIMI (P=0.009), whereas angiographic severity and extent of CAD independently predicted PSIMI.ConclusionsThe degree of digital microvascular constriction, and not the angiographic burden of CAD, is associated with MSIMI. Varying causes of MSIMI compared with PSIMI may require different therapeutic interventions that require further study.

Aims Mental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. Methods and Results We subjected 660 patients with stable CAD to 99mTc sestamibi myocardial perfusion imaging at rest, with mental (speech task) and with conventional (exercise/pharmacological) stress. Endothelium-dependent flow-mediated dilation (FMD), microvascular reactivity [reactive hyperemia index (RHI)] and arterial stiffness [pulse wave velocity (PWV)] were measured at rest and 30-min after mental stress. The digital microvascular vasomotor response during mental stress was assessed using peripheral arterial tonometry (PAT). A total of 106(16.1%) patients had MSIMI. Mental stress was accompanied by significant increases in rate-pressure-product (heart rate x systolic blood pressure; RPP), epinephrine levels and PWV, and significant decreases in FMD and PAT ratio denoting microvascular constriction. In comparison to those with no MSIMI, patients with MSIMI had higher hemodynamic and digital vasoconstrictive responses (p<0.05 for both), but did not differ in epinephrine, endothelial or macrovascular responses. Only presence of ischemia during conventional stress (OR of 7.1, 95%CI of 4.2, 11.9), high hemodynamic response (OR for RPP response ≥ vs < ROC cutoff of 1.8, 95%CI of 1.1, 2.8), and high digital vasoconstriction (OR for PAT ratio < vs ≥ ROC cutoff of 2.1, 95%CI of 1.3, 3.3) were independent predictors of MSIMI. Conclusion Ischemia during conventional stress testing and hemodynamic and vasoconstrictive responses to mental stress can help predict subjects with CAD at greater risk of developing MSIMI.

BackgroundEmerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI).Methods and ResultsWe studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress.ConclusionsYoung women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group.

Objective 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. Methods 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 99mTc sestamibi myocardial perfusion imaging. Patients also underwent conventional stress testing for myocardial ischemia (CSMI) 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. Results Six-hundred and ninety-five patients completed baseline enrollment in the MIPS. Their mean (SD) 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 are 16.1% and 34.7%, respectively. A total of 151 (22.9%) patients had only CSIMI, 28 (4.2%) had only MSIMI and 78 (11.8%) had both MSIMI and CISIMI. Patients with ischemia had a lower ejection fraction and higher prevalence of previous coronary artery bypass grafting compared to those without inducible ischemia (p<0.050). The prevalence of obstructive CAD was not statistically different between patients with and without MSIMI (p=0.426); in contrast, it was higher in patients with CSIMI (p<0.001). Conclusion The MIPS data will provide useful information to assess the prognostic significance and underlying mechanisms of MSIMI.

Women and men have distinct cardiovascular reactivity mechanisms for MSIMI. For women, stress-induced peripheral vasoconstriction with mental stress, and not increased hemodynamic workload, is associated with MSIMI, whereas for men, it is the opposite. Future studies should examine these pathways on long-term outcomes.

Rationale Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. Objective To examine the relationship between LTL and PCs, and their impact on adverse cardiovascular outcomes. Methods and Results We measured LTL by quantitative PCR in 566 outpatients (age 63±9 years, 76% male) with coronary artery disease (CAD). Circulating PCs were enumerated by flow cytometry. After adjustment for age, gender, race, BMI, smoking and previous myocardial infarction, a shorter LTL was associated with a lower CD34+ cell count: for each 10% shorter LTL, CD34+ levels were 5.2% lower (p<0.001). After adjustment for the aforementioned factors, both short LTL (