Relationship of Psychological Characteristics to Daily Life Ischemia: An Analysis From the National Heart, Lung, and Blood Institute Psychophysiological Investigations in Myocardial Ischemia.

OBJECTIVE: Cardiac ischemia during daily life is associated with an increased risk of adverse outcomes. Mental stress is known to provoke cardiac ischemia and is related to psychological variables. In this multicenter cohort study, we assessed whether psychological characteristics were associated with ischemia in daily life. METHODS: This study examined patients with clinically stable coronary artery disease (CAD) with documented cardiac ischemia during treadmill exercise (n = 196, mean [standard deviation] age = 62.64 [8.31] years; 13% women). Daily life ischemia (DLI) was assessed by 48-hour ambulatory electrocardiophic monitoring. Psychological characteristics were assessed using validated instruments to identify characteristics associated with ischemia occurring in daily life stress. RESULTS: High scores on anger and hostility were common in this sample of patients with CAD, and DLI was documented in 83 (42%) patients. However, the presence of DLI was associated with lower anger scores (odds ratio [OR] = 2.03; 95% confidence interval [CI] = 1.12-3.69), reduced anger expressiveness (OR = 2.04; 95% CI = 1.10-3.75), and increased ratio of anger control to total anger (OR = 2.33; 95% CI = 1.27-4.17). Increased risk of DLI was also associated with lower hostile attribution (OR = 2.22; 95% CI = 1.21-4.09), hostile affect (OR = 1.92; 95% CI = 1.03-3.58), and aggressive responding (OR = 2.26; 95% CI = 1.25-4.08). We observed weak inverse correlations between DLI episode frequency and anger expressiveness, total anger, and hostility scores. DLI was not associated with depression or anxiety measures. The combination of the constructs low anger expressiveness and low hostile attribution was independently associated with DLI (OR = = 2.59; 95% CI = 1.42-4.72). CONCLUSIONS: In clinically stable patients with CAD, the tendency to suppress angry and hostile feelings, particularly openly aggressive behavior, was associated with DLI. These findings warrant a study in larger cohorts, and intervention studies are needed to ascertain whether management strategies that modify these psychological characteristics improve outcomes.

Peripheral Vasoconstriction During Mental Stress and Adverse Cardiovascular Outcomes in Patients With Coronary Artery Disease.

RATIONALE: Excessive vasoconstriction in response to mental stress may be a potential mechanism by which acute psychological stress leads to adverse cardiac events. OBJECTIVES: We investigated whether excessive digital vasoconstriction during acute mental stress predicts adverse cardiovascular outcomes among patients with coronary artery disease. METHODS AND RESULTS: Five hundred forty-nine patients with stable coronary artery disease (age 63±9, 76% male, 29% black) underwent mental stress testing with a standardized public speaking stressor and followed prospectively for cardiovascular end points. Digital pulse wave amplitude was continuously measured using peripheral artery tonometry (PAT, Itamar Inc). Stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated and dichotomized by the median value into low and high sPAT ratio groups. Upon 3-year follow-up, Fine and Gray's subdistribution hazard ratios were used to examine the association between sPAT ratio and the composite end point of cardiovascular death, myocardial infarction, revascularization, and hospitalization for heart failure. The median sPAT ratio was 0.68 (interquartile range, 0.48-0.88), indicating 32% vasoconstriction with mental stress. Men were more likely to have low sPAT ratio than women (odds ratio, 1.79; P=0.007) while those on ß-blockers were less likely to have low sPAT ratio (odds ratio, 0.52; P=0.003). After adjusting for demographic and cardiovascular risk factors, medications, and rate-pressure product change during mental stress, those with low sPAT ratio were at significantly higher risk of adverse outcomes (subdistribution hazard ratio, 1.77 [95% CI, 1.12-2.80]). CONCLUSIONS: Greater peripheral vasoconstriction with mental stress, denoted by a low sPAT ratio, is associated with a higher risk of adverse cardiovascular outcomes in patients with coronary artery disease.

Association of Mental Stress-Induced Myocardial Ischemia With Cardiovascular Events in Patients With Coronary Heart Disease.

Importance: Mental 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. Objective: To compare the association of mental stress-induced or conventional stress-induced ischemia with adverse cardiovascular events in patients with CHD. Design, Setting, and Participants: Pooled 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). Exposures: Provocation 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 Measures: The 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. Results: Of 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 Relevance: Among 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.

The Impact of Past and Current Alcohol Consumption Patterns on Progression of Carotid Intima-Media Thickness Among Women and Men Living with HIV Infection.

BACKGROUND: The relationship between alcohol consumption and atherosclerosis has not been sufficiently examined among people living with HIV (PLWH). METHODS: We analyzed data from PLWH in the Women's Interagency HIV Study (WIHS; n = 1,164) and the Multicenter AIDS Cohort Study (MACS; n = 387) with no history of cardiovascular disease (CVD). Repeated measures of intima-media thickness of the right common carotid artery (CCA-IMT) were assessed using B-mode ultrasound from 2004 to 2013. Current alcohol consumption was collected at time of CCA-IMT measurement and was categorized according to gender-specific weekly limits. Group-based trajectory models categorized participants into past 10-year consumption patterns (1994 to 2004). Multivariate generalized estimating equations were conducted to assess the association of past and current alcohol use patterns on change in CCA-IMT by cohort, controlling for age, race, cigarette and illicit drug use, probable depression, HIV RNA viral load, antiretroviral therapy exposure, and hepatitis C coinfection. RESULTS: Among the WIHS, past heavy alcohol consumption was associated with increased CCA-IMT level over time (ß = 8.08, CI 0.35, 15.8, p = 0.04), compared to abstinence. Among the MACS, compared to abstinence, all past consumption patterns were associated with increased CCA-IMT over time (past low: ß = 15.3, 95% CI 6.46, 24.2, p < 0.001; past moderate: ß = 14.3, CI 1.36, 27.2, p = 0.03; past heavy: ß = 21.8, CI 4.63, 38.9, p = 0.01). Current heavy consumption was associated with decreased CCA-IMT among the WIHS (ß = -11.4, 95% CI -20.2, -2.63, p = 0.01) and MACS (ß = -15.4, 95% CI -30.7, -0.13, p = 0.04). No statistically significant time by consumption pattern effects were found. CONCLUSIONS: In both cohorts, 10-year heavy consumption was associated with statistically significant increases in carotid artery thickness, compared to abstinence. Long-term patterns of drinking at any level above abstinence were particularly significant for increases in IMT among men, with heavy consumption presenting with the greatest increase. Our results suggest a potentially different window of risk among past and current heavy drinkers. Further studies are needed to determine whether alcohol consumption level is associated with intermediate measures of atherosclerosis. Alcohol screening and interventions to reduce heavy consumption may benefit PLWH who are at risk of CVD.

Use of High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia: A Cohort Study.

Background: Many patients with coronary artery disease (CAD) are routinely referred for surveillance stress testing despite recommendations against it. Objective: To determine whether low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can identify persons without inducible myocardial ischemia. Design: Observational study. Setting: A university-affiliated hospital network. Patients: Persons with stable CAD: 589 in the derivation group and 118 in the validation cohort. Measurements: Presence of inducible myocardial ischemia was determined by myocardial perfusion imaging with technetium-99m single-photon emission computed tomography during either treadmill or pharmacologic stress testing. Resting plasma hs-cTnI was measured within 1 week of the stress test, and the negative predictive value (NPV) for inducible ischemia was calculated. The derivation cohort was followed for 3 years for incident cardiovascular death and myocardial infarction. Results: In the derivation cohort, 10 of 101 patients with an hs-cTnI level below 2.5 pg/mL had inducible myocardial ischemia (NPV, 90% [95% CI, 83% to 95%]) and 3 of 101 had inducible ischemia involving at least 10% of the myocardium (NPV, 97% [CI, 92% to 99%]). In the validation cohort, 4 of 32 patients with an hs-cTnI level below 2.5 pg/mL had inducible ischemia (NPV, 88% [CI, 71% to 96%]) and 2 of 32 had ischemia of 10% or greater (NPV, 94% [CI, 79% to 99%]). After a median follow-up of 3 years in the derivation cohort, no adverse events occurred in patients with an hs-cTnI level below 2.5 pg/mL, compared with 33 (7%) cardiovascular deaths or incident myocardial infarctions among those with an hs-cTnI level of 2.5 pg/mL or greater. Limitation: The data may not be applicable to a population without known CAD or to persons with unstable angina, and the modest sample sizes warrant further validation in a larger cohort. Conclusion: Very low hs-cTnI levels may be useful in excluding inducible myocardial ischemia in patients with stable CAD. Primary Funding Source: National Institutes of Health.

Inflammatory response to mental stress and mental stress induced myocardial ischemia.

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 ±â€¯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.

The Mental Stress Ischemia Prognosis Study: Objectives, Study Design, and Prevalence of Inducible Ischemia.

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 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. RESULTS: 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). CONCLUSIONS: The MIPS data will provide useful information to assess the prognostic significance and underlying mechanisms of MSIMI.

Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

BACKGROUND: Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. METHODS AND RESULTS: Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. CONCLUSIONS: Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

The association between alcohol use and cardiovascular disease among people living with HIV: a systematic review.

BACKGROUND: People living with HIV-infection (PLWH) have higher prevalence and earlier onset of cardiovascular disease (CVD), compared to uninfected populations. It is unclear how alcohol consumption is related to CVD among PLWH. OBJECTIVES: To summarize the current literature and strength of evidence regarding alcohol consumption as a risk factor for CVD among PLWH, to generate summary estimates for the effect of alcohol consumption on CVD outcomes, and to make recommendations for clinical practice and future research based on the findings and limitations of existing studies. METHODS: A systematic review was conducted using Pubmed/Medline to identify relevant peer-reviewed articles published between 1 January 1999 and 1 January 2014. After critical review of the literature, 13 studies were identified. Risk ratios were extracted or calculated and sample size weighted summary estimates were calculated. RESULTS: The prevalence of a CVD diagnosis or event ranged from 5.7-24.0%. The weighted pooled crude effect sizes were 1.75 (95% CI 1.06, 3.17) for general and 1.78 (95% CI 1.09, 2.93) for heavy alcohol use on CVD. The pooled adjusted effect size was 1.37 (95% CI 1.02, 1.84) for heavy alcohol use on CVD. Pooled estimates differed by CVD outcome and alcohol measure; alcohol consumption was most significant for cerebral/ischemic events. CONCLUSION: HIV clinicians should consider risk factors that are not included in the traditional risk factor framework, particularly heavy alcohol consumption. Neglect of this risk factor may lead to underestimation of risk, and thus under-treatment among PLWH.

Association of vitamin D status with mental stress-induced myocardial ischemia in patients with coronary artery disease.

BACKGROUND: Mental stress-induced (MSIMI) or physical stress-induced (PSIMI) myocardial ischemia portends a worse prognosis in patients with coronary artery disease (CAD). Vitamin D insufficiency is associated with adverse cardiovascular outcomes, but its relationship to myocardial ischemia remains unclear. We hypothesized that vitamin D insufficiency will be associated with a higher prevalence of myocardial ischemia in patients with CAD. METHODS: In 255 patients with stable CAD, myocardial perfusion imaging was performed to assess ischemia in response to mental and physical stress protocols. Vitamin D insufficiency was defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 30 ng/ml, collected on the day of stress testing. RESULTS: Mean (standard deviation) 25(OH)D level was 30.8 (12.8) ng/ml, and 139 (55%) patients had vitamin D insufficiency. MSIMI occurred in 30 (12%) patients and PSIMI in 67 (27%). Individuals with MSIMI had significantly lower levels of 25(OH)D as compared with those without MSIMI (24.0 [8.6] versus 31.7 [12.9], p = .002). The prevalence of MSIMI was higher in those with as compared with those without vitamin D insufficiency (17% versus 6%, p = .009). Moreover, low 25(OH)D levels remained independently associated with MSIMI after adjusting for potential confounders. Conversely, 25(OH)D levels were similar between those with or without PSIMI (29.8 [13.0] versus 31.4 [12.7], p = .37), as was the prevalence of PSIMI in those with or without vitamin D insufficiency (29% versus 24%, p = .42). CONCLUSIONS: Vitamin D insufficiency is associated with a higher prevalence of MSIMI but not PSIMI among stable patients with CAD. Whether this association serves as a potential mechanism linking low vitamin D status to adverse cardiovascular outcomes warrants further investigation.

Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress.

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.

Relation of High-sensitivity Cardiac Troponin I Elevation With Exercise to Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

High sensitive cardiac troponin I (hs-cTnI) increases with inducible myocardial ischemia in patients with coronary artery disease (CAD). We aimed to assess if the change in hs-cTnI levels with exercise stress testing is associated with major adverse cardiac events (MACE). A cohort of 365 (age 62 ± 9 years, 77% men) patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging with treadmill testing. Plasma hs-cTnI level was measured at rest and at 45 min after stress. Multivariable Fine & Gray's subdistribution hazards models were used to determine the association between the change in hs-cTnI and MACE, a composite end point of cardiovascular death, myocardial infarction, and unstable angina requiring revascularization. During a median follow-up of 3 years, 39 (11%) patients experienced MACE. After adjustment, for each two-fold increment in hs-cTnI with stress, there was a 2.2 (95% confidence interval 1.3-3.6)-fold increase in the hazard for MACE. Presence of both a high resting hs-cTnI level (>median) and ≥ 20% stress-induced hs-cTnI elevation was associated with the highest incidence of MACE (subdistribution hazards models 4.6, 95% confidence interval 1.6 to 13.0) compared with low levels of both. Risk discrimination statistics significantly improved after addition of resting and change in hs-cTnI levels to a model including traditional risk factors and inducible ischemia (0.67 to 0.71). Conversely, adding inducible ischemia by SPECT did not significantly improve the C-statistic from a model including traditional risk factors, baseline and change in hs-cTnI (0.70 to 0.71). In stable CAD patients, higher resting levels and elevation of hs-cTnI with exercise are predictors of adverse cardiovascular outcomes beyond traditional cardiovascular risk factors and presence of inducible ischemia.

Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.

Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

Psychobiology of depression/distress in congestive heart failure.

Heart failure affects millions of Americans and new diagnosis rates are expected to almost triple over the next 30 years as our population ages. Affective disorders including clinical depression and anxiety are common in patients with congestive heart failure. Furthermore, the presence of these disorders significantly impacts quality of life, medical outcomes, and healthcare service utilization. In recent years, the literature has attempted to describe potential pathophysiologic mechanisms relating affective disorders and psychosocial stress to heart failure. Several potential mechanisms have been proposed including autonomic nervous system dysfunction, inflammation, cardiac arrhythmias, and altered platelet function. These mechanisms are reviewed in this article. Additional novel mechanisms such as mental stress-induced myocardial ischemia are also discussed.

The effect of acute psychological stress on QT dispersion in patients with coronary artery disease.

BACKGROUND: An acute psychological stress can precipitate ventricular arrhythmias and sudden cardiac death in patients with coronary artery disease (CAD). However, the physiologic mechanisms by which these effects occur are not entirely clear. Mental stress-induced myocardial ischemia occurs in a significant percentage of the CAD population. It is unknown if the proarrhythmic effects of psychological stress are mediated through the development of myocardial ischemia. OBJECTIVES: To examine the effects of psychological stress on QT dispersion (QTd) among CAD patients and whether these effects are mediated via the development of myocardial ischemia. METHODS: Psychological stress was induced using a public speaking task. Twelve-lead electrocardiograms (ECG) were recorded at rest, during mental stress, and during recovery. QTd was calculated as the difference between the longest and the shortest QT interval in the 12-lead ECG. Rest-stress myocardial perfusion imaging was also performed to detect mental stress-induced myocardial ischemia. RESULTS: Mental stress induced a significant increase in QTd compared to the resting condition (P < 0.001). This effect persisted beyond the first 10 minutes of recovery (P < 0.001). QTd was significantly associated with the development of mental stress ischemia with ischemic patients having significantly higher QTd during mental stress than nonischemic patients (P = 0.006). This finding remained significant after controlling for possible confounding factors (P = 0.01). CONCLUSION: An acute psychological stress induces a significant increase in QTd, which persists for more than 10 minutes after the cessation of the stressor. This effect seems to be, at least partially, mediated by the development of mental stress-induced myocardial ischemia.

Association of beta1-adrenergic receptor genetic polymorphism with mental stress-induced myocardial ischemia in patients with coronary artery disease.

BACKGROUND: Mental stress is associated with sympathetic adrenergic stimulation and concomitant increases in blood pressure and heart rate. Heritable individual differences in cardiovascular functional response to mental stress may arise from genetic variations in adrenergic receptors, which might produce excessive hemodynamic response to mental stress or create other conditions favoring the development of myocardial ischemia. METHODS: We examined the relationship between hemodynamic response to mental stress and mental stress-induced myocardial ischemia (MSIMI) and 5 common functional polymorphisms of beta1-adrenergic receptors (ADRB1 [OMIM 109630, accession No. 153]) and beta2-adrenergic receptors (ADRB2 [OMIM 109690, accession No. 154]). Participants were 148 patients (45 female [30.4%]) with a documented history of coronary artery disease and a mean (SD) age of 64 (9) years. Patients were enrolled between December 9, 2004, and February 21, 2007. Mental stress was induced via a public-speaking task. Rest and stress myocardial perfusion imaging was performed. Blood samples were collected and genotyped for 5 common functional polymorphisms of ADRB1 (codons 49 and 389) and ADRB2 (codons 16 and 27 and nucleotide 523). The main outcome measures were hemodynamic and myocardial ischemic responses to mental stress. Mental stress-induced myocardial ischemia was defined as new or worsening perfusion defects during mental stress with a summed (stress to rest) difference score of at least 3. RESULTS: A statistically significant difference was noted in the prevalences of MSIMI between genotype groups for codon 49 of ADRB1. Mental stress-induced myocardial ischemia occurred 3 times more frequently among patients homozygous for the Ser49 allele (31 of 104 patients [29.8%]) compared with 4 of 39 patients (10.3%) among the Gly49 allele carriers (P=.02). The adjusted odds ratio for the effect of genotype (Ser/Ser vs Gly carriers) on MSIMI was 3.9 (95% confidence interval, 1.2-12.5) (P=.02). CONCLUSIONS: Our findings indicate an association between a common genetic variation in ADRB1 and myocardial ischemic response to mental stress in patients with coronary artery disease. This polymorphic genetic marker may help identify patients at increased risk for mental stress-induced adverse outcomes.

AHA science advisory. Depression and coronary heart disease. Recommendations for screening, referral, and treatment. A science advisory from the American Heart Association Prevention Committee to the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care Outcomes Research. Endorsed by the American Psychiatric Association.

Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

Association of Transient Endothelial Dysfunction Induced by Mental Stress With Major Adverse Cardiovascular Events in Men and Women With Coronary Artery Disease.

Importance: Acute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown. Objective: To determine the association between mental stress-induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes among individuals with stable coronary artery disease. Design, Setting, and Participants: This cohort study was conducted at a university-affiliated hospital network between June 2011 and August 2014. A cohort of individuals with stable coronary artery disease were included. Data analysis took place from November 2018 to May 2019. Exposures: Study participants were subjected to a laboratory mental stress task (public speaking). Main Outcomes and Measures: Flow-mediated vasodilation was measured before and 30 minutes after a public-speaking mental stress task. We examined the association of the rest (prestress), poststress, and δ flow-mediated vasodilation (poststress minus prestress levels) with an adjudicated composite end point of adverse events, including cardiovascular death, myocardial infarction, unstable angina leading to revascularization, and heart failure hospitalization, after adjusting for sociodemographic factors, medical history, and depression. Results: A total of 569 patients were included (mean [SD] age, 62.6 [9.3] years; 420 men [73.8%]). Flow-mediated vasodilation decreased from a mean (SD) of 4.8% (3.7%) before mental stress to 3.9% (3.6%) after mental stress (a 23% reduction; P < .001), and 360 participants (63.3%) developed transient endothelial dysfunction (a decrease in flow-mediated vasodilation). During a median (interquartile range) follow-up period of 3.0 (2.9-3.1) years, 74 patients experienced a major adverse cardiovascular event. The presence of transient endothelial dysfunction with mental stress was associated with a 78% increase (subdistribution hazard ratio [sHR], 1.78 [95% CI, 1.15-2.76]) in the incidence of major adverse cardiovascular event. Both the δ flow-mediated vasodilation (sHR, 1.15 [95% CI, 1.03-1.27] for each 1% decline) and poststress flow-mediated vasodilation (sHR, 1.14 [95% CI, 1.04-1.24] for each 1% decline) were associated with major adverse cardiovascular event. Risk discrimination statistics demonstrated a significant model improvement after addition of either poststress flow-mediated vasodilation (change in the area under the curve, 0.05 [95% CI, 0.01-0.09]) or prestress plus δ flow-mediated vasodilation (change in the area under the curve, 0.04 [95% CI, 0.00-0.08]) compared with conventional risk factors. Conclusions and Relevance: In this study, transient endothelial dysfunction with mental stress was associated with adverse cardiovascular outcomes in patients with coronary artery disease. Endothelial responses to stress represent a possible mechanism through which psychological stress may affect outcomes in patients with coronary artery disease.

Depressive symptoms predict heart rate recovery after exercise treadmill testing in patients with coronary artery disease: results from the Psychophysiological Investigation of Myocardial Ischemia study.

BACKGROUND: Depression is associated with increased risk of death among patients with coronary disease. Cardiovascular autonomic dysregulation may be one of the mechanisms by which depression exerts its effects on cardiovascular function. The purpose of this study was to determine whether depressive symptoms are associated with low heart rate variability (HRV) and prolonged HR recovery after exercise testing in patients with coronary artery disease (CAD). METHODS: The Psychophysiological Investigation of Myocardial Ischemia (PIMI) was a large, multicenter study designed to assess psychological and physiological correlates of stress in patients with CAD. One hundred and eighty-eight patients with CAD as evidenced by at least 50% blockage of one major artery and a previous positive exercise stress test were included in this study. Patients included in this report were not taking beta blockers. Cardiovascular functioning was assessed by a modified Bruce protocol treadmill stress test. Measures of psychological functioning, including the Beck Depression Inventory (BDI), were also obtained. RESULTS: BDI scores were negatively correlated with HR recovery (r = -0.15, p = .04). Depression scores accounted for 3.5% of the variance in HR recovery when controlling for participant age (p < .01). Depressive symptoms were related to two HRV indices (ultra-low frequency, high frequency). CONCLUSIONS: Depressive symptoms are associated with cardiovascular autonomic nervous system dysfunction as assessed by HR recovery. This relationship is not merely due to an association of depression severity with beta blocker usage or a failure of depressed patients to achieve an adequate chronotropic response.

Depression, the metabolic syndrome and cardiovascular risk.

BACKGROUND: The relationship between depression and the metabolic syndrome is unclear, and whether metabolic syndrome explains the association between depression and cardiovascular disease (CVD) risk is unknown. METHODS: We studied 652 women who received coronary angiography as part of the Women's Ischemia Syndrome Evaluation (WISE) study and completed the Beck Depression Inventory (BDI). Women who had both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression were considered at highest risk, whereas those with one of the two conditions represented an intermediate group. The metabolic syndrome was defined according to the ATP-III criteria. The main outcome was incidence of adverse CVD events (hospitalizations for myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over a median follow-up of 5.9 years. RESULTS: After adjusting for demographic factors, lifestyle and functional status, both depression categories were associated with about 60% increased odds for metabolic syndrome compared with no depression (p = .03). The number of metabolic syndrome risk factors increased gradually across the three depression categories (p = .003). During follow-up, 104 women (15.9%) experienced CVD events. In multivariable analysis, women with both elevated symptoms and a previous diagnosis of depression had 2.6 times higher risk of CVD. When metabolic syndrome was added to the model, the risk associated with depression only decreased by 7%, and both depression and metabolic syndrome remained significant predictors of CVD. CONCLUSIONS: In women with suspected coronary artery disease, the metabolic syndrome is independently associated with depression but explains only a small portion of the association between depression and incident CVD.