Sex-Specific Association Between Coronary Artery Disease Severity and Myocardial Ischemia Induced by Mental Stress.
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ABSTRACT:
SUBMITTER: Almuwaqqat Z
PROVIDER: S-EPMC6800112 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Sex-Specific Association Between Coronary Artery Disease Severity and Myocardial Ischemia Induced by Mental Stress.
Almuwaqqat Zakaria Z Sullivan Samaah S Hammadah Muhammad M Lima Bruno B BB Shah Amit J AJ Abdelhadi Naser N Fang Shuyang S Wilmot Kobina K Al Mheid Ibhar I Bremner J Douglas JD Garcia Ernest E Nye Jonathon A JA Elon Lisa L Li Lian L OʼNeal Wesley T WT Raggi Paolo P Quyyumi Arshed A AA Vaccarino Viola V
Psychosomatic medicine 20190101 1
<h4>Objective</h4>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.<h4>Methods</h4>We studied 276 patients 61 years and younger with recent myocardial infarction. CAD severity was quantified usin ...[more]
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Project description:BACKGROUND:Mental stress-induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease. Women with coronary artery disease tend to have more mental stress-induced myocardial ischemia and more chest pain/anginal symptoms than men, but whether the association between mental stress-induced myocardial ischemia and angina burden differs in women and men is unknown. METHODS:This was a cross-sectional study with experimental manipulation of 950 individuals with stable coronary artery disease. Chest pain/angina frequency in the previous 4 weeks was assessed with the Seattle Angina Questionnaire's angina-frequency subscale. Mental stress-induced myocardial ischemia was assessed with myocardial perfusion imaging during mental stress (standardized public speaking task). Presence of mental stress-induced myocardial ischemia was based on expert readers and established criteria. A conventional (exercise or pharmacologic) stress test was used as a control condition. RESULTS:Overall, 338 individuals (37%) reported angina; 112 (12%) developed mental stress-induced myocardial ischemia, and 256 (29%) developed conventional stress ischemia. Women who reported angina had almost double the probability to develop mental stress-induced myocardial ischemia (19% vs 10%, adjusted prevalence rate ratio, 1.90; 95% confidence interval, 1.04-3.46), whereas there was no such difference in men (11% vs 11%, adjusted prevalence rate ratio, 1.09; 95% confidence interval, 0.66-1.82). No association was found between angina symptoms and conventional stress ischemia for women or men. Results for ischemia as a continuous variable were similar. CONCLUSIONS:In women, but not in men, anginal symptoms may be a marker of vulnerability toward ischemia induced by psychologic stress. These results highlight the psychosocial origins of angina in women and may have important implications for the management and prognosis of women with angina.
| S-EPMC5910270 | biostudies-literature
Project description: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.
| S-EPMC4126399 | biostudies-literature
Project description:ImportanceMental stress-induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated.ObjectiveTo compare the association of mental stress-induced or conventional stress-induced ischemia with adverse cardiovascular events in patients with CHD.Design, setting, and participantsPooled analysis of 2 prospective cohort studies of patients with stable CHD from a university-based hospital network in Atlanta, Georgia: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 (last follow-up, February 2020).ExposuresProvocation of myocardial ischemia with a standardized mental stress test (public speaking task) and with a conventional (exercise or pharmacological) stress test, using single-photon emission computed tomography.Main outcomes and measuresThe primary outcome was a composite of cardiovascular death or first or recurrent nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure.ResultsOf the 918 patients in the total sample pool (mean age, 60 years; 34% women), 618 participated in MIPS and 300 in MIMS2. Of those, 147 patients (16%) had mental stress-induced ischemia, 281 (31%) conventional stress ischemia, and 96 (10%) had both. Over a 5-year median follow-up, the primary end point occurred in 156 participants. The pooled event rate was 6.9 per 100 patient-years among patients with and 2.6 per 100 patient-years among patients without mental stress-induced ischemia. The multivariable adjusted hazard ratio (HR) for patients with vs those without mental stress-induced ischemia was 2.5 (95% CI, 1.8-3.5). Compared with patients with no ischemia (event rate, 2.3 per 100 patient-years), patients with mental stress-induced ischemia alone had a significantly increased risk (event rate, 4.8 per 100 patient-years; HR, 2.0; 95% CI, 1.1-3.7) as did patients with both mental stress ischemia and conventional stress ischemia (event rate, 8.1 per 100 patient-years; HR, 3.8; 95% CI, 2.6-5.6). Patients with conventional stress ischemia alone did not have a significantly increased risk (event rate, 3.1 per 100 patient-years; HR, 1.4; 95% CI, 0.9-2.1). Patients with both mental stress ischemia and conventional stress ischemia had an elevated risk compared with patients with conventional stress ischemia alone (HR, 2.7; 95% CI, 1.7-4.3). The secondary end point occurred in 319 participants. The event rate was 12.6 per 100 patient-years for patients with and 5.6 per 100 patient-years for patients without mental stress-induced ischemia (adjusted HR, 2.0; 95% CI, 1.5-2.5).Conclusions and relevanceAmong patients with stable coronary heart disease, the presence of mental stress-induced ischemia, compared with no mental stress-induced ischemia, was significantly associated with an increased risk of cardiovascular death or nonfatal myocardial infarction. Although these findings may provide insights into mechanisms of myocardial ischemia, further research is needed to assess whether testing for mental stress-induced ischemia has clinical value.
| S-EPMC8579237 | biostudies-literature
Project description:ImportanceThe long-term prognostic implications of myocardial ischemia documented during stress testing in patients with multivessel coronary artery disease (CAD) are unclear.ObjectiveTo assess whether documented stress testing-induced myocardial ischemia is associated with major adverse cardiovascular events or ventricular function changes in patients with stable multivessel CAD.Design, setting, and participantsA prospective cohort study was conducted using data from a single-center randomized clinical trial (Medicine, Angioplasty, or Surgery Study [MASS] II) to examine the association of myocardial ischemia documented during stress testing at baseline with cardiovascular events and ventricular function changes during follow-up. Participants were previously randomized (May 1, 1995, to May 31, 2000) to medical therapy, percutaneous coronary intervention with bare metal stents, or coronary artery bypass grafting. Event-free survival was estimated by the Kaplan-Meier method, and multivariable Cox regression models were calculated to assess the association between ischemia and the primary composite end point. The vital status was determined on February 28, 2011. Data were analyzed from February 1, 2016, to April 1, 2017.Main outcomes and measuresCardiovascular events (overall mortality, myocardial infarction, and revascularization for refractory angina) were tracked from the time of randomization to the end of the 10-year follow-up (mean [SD] duration, 11.4 [4.3] years). Myocardial ischemia was assessed at baseline and at 1-year intervals by exercise stress testing, and ventricular function (left ventricular ejection fraction) was assessed by echocardiography at baseline and after 10 years. Patients with documented ischemia were compared with those without ischemia regarding the outcomes and changes in ventricular function.ResultsOf 611 participants, 535 underwent exercise stress testing at baseline: 270 with documented ischemia and 265 without. Of these 535 patients, 373 (69.7%) were men, and the mean (SD) age for the entire cohort was 59.7 (9.2) years. No association was found between the presence of ischemia at baseline and survival free of combined cardiovascular events (hazard ratio, 1.00; 95% CI, 0.80-1.27; P = .95) after multivariable adjustment that included CAD initial randomized treatments. In addition, among 320 patients who underwent echocardiographic evaluation, the slight decline in left ventricular ejection fraction after 10 years was similar in both groups (median [SD] difference, -4.9% [18.7%] vs -6.6% [20.0%], respectively, for groups with and without ischemia; P = .97).Conclusions and relevanceIn this study, regardless of the therapeutic strategy applied, the presence of documented myocardial ischemia did not appear to be associated with an increased occurrence of major adverse cardiovascular events or changes in ventricular function in patients with multivessel CAD during a long-term follow-up.
| S-EPMC6647357 | biostudies-literature
Project description:ImportancePosttraumatic stress disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear.ObjectiveTo evaluate the association of PTSD with mental stress-induced myocardial ischemia among individuals who survived a myocardial infarction (MI).Design, setting, and participantsThis cross-sectional study included 303 patients aged 18 to 60 years enrolled from a university-affiliated network. Participants had a verified history of MI within 8 months. Data were collected from June 2011 to March 2016, and data analysis was conducted from March to June 2019.ExposuresA clinical diagnosis of PTSD (lifetime and current) was obtained using the Structured Clinical Interview from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and PTSD symptom subscales were assessed with the civilian version of the PTSD Symptom Checklist.Main outcomes and measuresPatients received technetium 99m-labeled sestamibi myocardial perfusion imaging at rest, with mental stress (ie, a speech task) and conventional stress (ie, exercise or pharmacologic). A summed difference score (ie, the difference between stress and rest scores) was used to assess ischemia under both stress conditions.ResultsAmong 303 participants (148 [48.8%] women; 198 [65.3%] African American; mean [SD] age, 51 [7] years), the prevalence of PTSD was 14.5% (44 patients). Patients with PTSD had a higher rate of ischemia with mental stress than those without PTSD (12 of 44 [27.3%] vs 38 of 259 [14.7%]; P = .04) and more than twice the mean number of ischemic segments (1.2 [95% CI, 0.5-1.8] vs 0.5 [95% CI, 0.3-0.7]; P < .001), but there was no difference in conventional stress ischemia (10 of 44 [22.7%] vs 60 of 259 [23.2%]; P = .91). Increasing levels of PTSD symptoms were associated with higher odds of ischemia with mental stress (adjusted odds ratio [OR] per 5-point score increase, 1.18; 95% CI 1.04-1.35; P = .01) but not with conventional stress (adjusted OR per 5-point score increase, 1.05; 95% CI, 0.92-1.21; P = .47). Reexperiencing trauma was the symptom cluster most robustly associated with the presence of ischemia with mental stress (adjusted OR per 5-point score increase, 1.87; 95% CI 1.21-2.91; P = .005), followed by avoidance and numbing (adjusted OR per 5-point score increase, 1.51; 95% CI, 1.07-2.14; P = .02).Conclusions and relevanceIn this study of young and middle-aged individuals with MI, with a large representation of women and patients from racial/ethnic minority groups, PTSD was associated with the development of myocardial ischemia with mental stress. A higher ischemic response to mental stress represents a potential pathway associating PTSD with adverse outcomes after MI.
| S-EPMC7156990 | biostudies-literature
Project description:ImportanceWhile many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.ObjectiveTo describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.Design, setting, and participantsThis secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.InterventionsCCTA and angina assessment.Main outcomes and measuresSex differences in stress test, CCTA findings, and symptom severity.ResultsOf 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).Conclusions and relevanceWomen in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.Trial registrationClinicalTrials.gov Identifier: NCT01471522.
| S-EPMC7105951 | biostudies-literature
Project description:BACKGROUND:Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothesized that patients with MSIMI would have a higher inflammatory response to mental stress in comparison to those without ischemia. METHODS:Patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during mental stress testing using a public speaking stressor. MSIMI was determined as impaired myocardial perfusion using a 17-segment model. Inflammatory markers including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metallopeptidase 9 (MMP-9) and high-sensitivity C reactive protein (hsCRP) were measured at rest and 90?min after mental stress. Results were validated in an independent sample of 228 post-myocardial infarction patients. RESULTS:Of 607 patients analyzed in this study, (mean age 63?±?9?years, 76% male), 99 (16.3%) developed MSIMI. Mental stress resulted in a significant increase in IL-6, MCP-1, and MMP-9 (all p?<0.0001), but not hsCRP. However, the changes in these markers were similar in those with and without MSIMI. Neither resting levels of these biomarkers, nor their changes with mental stress were significantly associated with MSIMI. Results in the replication sample were similar. CONCLUSION:Mental stress is associated with acute increases in several inflammatory markers. However, neither the baseline inflammatory status nor the magnitude of the inflammatory response to mental stress over 90?min were significantly associated with MSIMI.
| S-EPMC5808921 | biostudies-literature
Project description:OBJECTIVE:To investigate sex-specific vascular mechanisms for mental stress-induced myocardial ischemia (MSIMI). APPROACH AND RESULTS:Baseline data from a prospective cohort study of 678 patients with coronary artery disease underwent myocardial perfusion imaging before and during a public speaking stressor. The rate-pressure product response was calculated as the difference between the maximum value during the speech minus the minimum value during rest. Peripheral vasoconstriction by peripheral arterial tonometry was calculated as the ratio of pulse wave amplitude during the speech over the resting baseline; ratios <1 indicate a vasoconstrictive response. MSIMI was defined as percent of left ventricle that was ischemic and as a dichotomous variable. Men (but not women) with MSIMI had a higher rate-pressure product response than those without MSIMI (6500 versus 4800 mm?Hg bpm), whereas women (but not men) with MSIMI had a significantly lower peripheral arterial tonometry ratio than those without MSIMI (0.5 versus 0.8). In adjusted linear regression, each 1000-U increase in rate-pressure product response was associated with 0.32% (95% confidence interval, 0.22-0.42) increase in inducible ischemia among men, whereas each 0.10-U decrease in peripheral arterial tonometry ratio was associated with 0.23% (95% confidence interval, 0.11-0.35) increase in inducible myocardial ischemia among women. Results were independent of conventional stress-induced myocardial ischemia. CONCLUSIONS: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.
| S-EPMC5785428 | biostudies-literature
Project description:BackgroundThe ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.MethodsIn total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest).ResultsRelative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar.ConclusionsIschemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.
| S-EPMC8478888 | biostudies-literature
Project description:OBJECTIVES:This study sought to investigate whether patients with mental stress-induced myocardial ischemia will have high resting and post-mental stress high-sensitivity cardiac troponin I (hs-cTnI). BACKGROUND:Hs-cTnI is a marker of myocardial necrosis, and its elevated levels are associated with adverse outcomes. Hs-cTnI levels may increase with exercise in patients with coronary artery disease. Mental stress-induced myocardial ischemia is also linked to adverse outcomes. METHODS:In this study, 587 patients with stable coronary artery disease underwent technetium Tc 99m sestamibi-single-photon emission tomography myocardial perfusion imaging during mental stress testing using a public speaking task and during conventional (pharmacological/exercise) stress testing as a control condition. Ischemia was defined as new/worsening impairment in myocardial perfusion using a 17-segment model. RESULTS:The median hs-cTnI resting level was 4.3 (interquartile range [IQR]: 2.9 to 7.3) pg/ml. Overall, 16% and 34.8% of patients developed myocardial ischemia during mental and conventional stress, respectively. Compared with those without ischemia, median resting hs-cTnI levels were higher in patients who developed ischemia either during mental stress (5.9 [IQR: 3.9 to 8.3] pg/ml vs. 4.1 [IQR: 2.7 to 7.0] pg/ml; p < 0.001) or during conventional stress (5.4 [IQR: 3.9 to 9.3] pg/ml vs. 3.9 [IQR: 2.5 to 6.5] pg/ml; p < 0.001). Patients with high hs-cTnI (cutoff of 4.6 pg/ml for men and 3.9 pg/ml for women) had greater odds of developing mental (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.5 to 3.9; p < 0.001) and conventional (OR: 2.4; 95% CI: 1.7 to 3.4; p < 0.001) stress-induced ischemia. Although there was a significant increase in 45-min post-treadmill exercise hs-cTnI levels in those who developed ischemia, there was no significant increase after mental or pharmacological stress test. CONCLUSIONS:In patients with coronary artery disease, myocardial ischemia during either mental stress or conventional stress is associated with higher resting levels of hs-cTnI. This suggests that hs-cTnI elevation is an indicator of chronic ischemic burden experienced during everyday life. Whether elevated hs-cTnI levels are an indicator of adverse prognosis beyond inducible ischemia or whether it is amenable to intervention requires further investigation.
| S-EPMC5814354 | biostudies-literature