Kaki M. York

Coronary artery disease and depression : Patients with more depressive symptoms have lower cardiovascular reactivity during laboratory-induced mental stress

Objective: To investigate the relationship between symptoms of depression and cardiovascular reactivity during mental stress in patients with coronary artery disease (CAD). Depressive symptoms are common in patients with CAD and are related to an increased risk of cardiac events and death. Some researchers have proposed that negative outcomes in depressed patients with CAD may be related to exaggerated cardiovascular reactivity and psychological stress. However, the data are unclear. Methods: Patients with CAD (n = 128; mean age = 64 years) were recruited for this study. Participants underwent psychological stress testing and 2-day (stress/rest) radionuclide imaging. The Beck Depression Inventory (BDI) results were collected at baseline. Cardiac function data were also gathered and stress data were compared with baseline findings. Results: The change in systolic blood pressure (SBP) from rest to stress was 47 ± 18 (mean ± standard deviation) mm Hg, diastolic blood pressure (DBP) = 30 ± 11 mm Hg, double product difference (DP) = 5887 ± 3095, and heart rate (HR) = 20 ± 13 beats/minute (p < .001 for all). The BDI score was 8.7 ± 5.6. The BDI score was negatively correlated with all hemodynamic variables, although only significant with stress SBP and DP, and HR and DP changes. BDI scores also predicted changes in HR and DP. HR remained significant in regression analyses controlling for other sample characteristics. Conclusions: This study showed a negative relationship between depressive symptoms and cardiovascular reactivity to mental stress. In contrast to the mechanism proposed by earlier researchers, this study suggests that decreased cardiovascular reactivity occurs with increased depressive symptomology. The mechanism by which this effect occurs and its clinical significance are still unknown. BDI = Beck Depression Inventory; SBP = systolic blood pressure; DBP = diastolic blood pressure; DP = double product difference; HR = heart rate.

Social networks and incident stroke among women with suspected myocardial ischemia

Objective: To describe the prospective relationship between social networks and nonfatal stroke events in a sample of women with suspected myocardial ischemia. Social networks are an independent predictor of all-cause and cardiovascular mortality, but their relationship with stroke events in at-risk populations is largely unknown. Method: A total of 629 women (mean age = 59.6 ± 11.6 years) were evaluated at baseline for cardiovascular disease risk factors as part of a protocol including coronary angiography; the subjects were followed over a median 5.9 years to track the incidence of cardiovascular events including stroke. Participants also completed the Social Network Index (SNI), measuring the presence/absence of 12 types of common social relationships. Results: Stroke events occurred among 5.1% of the sample over follow-up. More isolated women were older and less educated, with higher rates of smoking and hypertension, and increased use of cardiovascular medications. Women with smaller social networks were also more likely to show elevations (scores of ≥10) on the Beck Depression Inventory (54% versus 41%, respectively; p = .003). Relative to women with higher SNI scores, Cox regression results indicated that more isolated women experienced strokes at greater than twice the rate of those with more social relationships after adjusting for covariates (hazard ratio = 2.7; 95% Confidence Interval = 1.1–6.7). Conclusions: Smaller social networks are a robust predictor of stroke in at-risk women, and the magnitude of the association rivals that of conventional risk factors. CAD = coronary artery disease; SES = socioeconomic status; CVD = cardiovascular disease; WISE = Womens Ischemia Syndrome Evaluation; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; SNI = Social Network Index; BDI = Beck Depression Inventory; HR = hazard ratio.

Psychotropic medication use and risk of adverse cardiovascular events in women with suspected coronary artery disease: outcomes from the Women’s Ischemia Syndrome Evaluation (WISE) study

Objective: This study investigated the relation between psychotropic medication use and adverse cardiovascular (CV) events in women with symptoms of myocardial ischaemia undergoing coronary angiography. Method: Women enrolled in the Women’s Ischemia Syndrome Evaluation (WISE) were classified into one of four groups according to their reported antidepressant and anxiolytic medication usage at study intake: (1) no medication (n = 352); (2) anxiolytics only (n = 67); (3) antidepressants only (n = 58); and (4) combined antidepressant and anxiolytics (n = 39). Participants were followed prospectively for the development of adverse CV events (for example, hospitalisations for non-fatal myocardial infarction, stroke, congestive heart failure and unstable angina) or all-cause mortality over a median of 5.9 years. Results: Use of antidepressant medication was associated with subsequent CV events (HR 2.16, 95% CI 1.21 to 3.93) and death (HR 2.15, 95% CI 1.16 to 3.98) but baseline anxiolytic use alone did not predict subsequent CV events and death. In a final regression model that included demographics, depression and anxiety symptoms, and risk factors for cardiovascular disease, women in the combined medication group (that is, antidepressants and anxiolytics) had higher risk for CV events (HR 3.98, CI 1.74 to 9.10, p = 0.001 and all-cause mortality (HR 4.70, CI 1.7 to 2.97, p = 0.003) compared to those using neither medication. Kaplan-Meier survival curves indicated that there was a significant difference in mortality among the four medication groups (p = 0.001). Conclusions: These data suggest that factors related to psychotropic medication such as depression refractory to treatment, or medication use itself, are associated with adverse CV events in women with suspected myocardial ischaemia.

Depressive Symptoms Predict Heart Rate Recovery After Exercise Treadmill Testing in Patients With Coronary Artery Disease : Results From the Psychophysiological Investigations 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. ANS = autonomic nervous system; CAD = coronary artery disease; HR = heart rate; HRV = heart rate variability; PIMI = Psychophysiological Investigation of Myocardial Ischemia

Variability of myocardial ischemic responses to mental versus exercise or adenosine stress in patients with coronary artery disease.

Background. Mental stress precipitates myocardial ischemia in a significant percentage of coronary artery disease (CAD) patients. Exercise or adenosine stresses produce different physiologic responses and cause myocardial ischemia via different mechanisms. Little is known about the comparative severity and location of myocardial ischemia provoked by these different stressors. In this study we sought to compare the within-individual ischemic responses to mental versus exercise or adenosine stress in a cohort of CAD patients.Methods and Results. All patients underwent mental stress and either exercise or adenosine testing within a 1-week period. Mental stress was induced via a public speaking task. Rest-stress myocardial perfusion imaging was used with all testing protocols. Participants were 187 patients (65 women [35%]) with a documented history of CAD and a mean age of 64 ± 9 years. Mental stress-induced myocardial ischemia (MSIMI) was less prevalent and frequently of less magnitude than exercise- or adenosine-induced ischemia. Ischemia induced by exercise or adenosine testing did not accurately predict the development or the location of MSIMI. The overall concordance between these stressors for provoking ischemia was weak (percent agreement, 71%; κ [± SE], 0.26 ± 0.07). In a minority of patients (11%) mental stress provoked ischemia in the absence of exercise- or adenosine-induced ischemia. Moreover, in patients who had myocardial ischemia during both stressors, there were significant within-individual differences in the coronary artery distribution of the ischemic regions. MSIMI was more likely to occur in a single-vessel distribution (86%) compared with exercise- or adenosine-induced ischemia (54%). The stressors had moderate agreement if the ischemic region was in the right coronary artery territory (percent agreement, 76%; κ, 0.52 ± 0.19) or the left anterior descending coronary artery (percent agreement, 76%; κ, 0.51 ± 0.19) and significantly lower agreement in the left circumflex territory (percent agreement, 62%; κ, 0.22 ± 0.18).Conclusions. Our findings indicate that mental and exercise or adenosine stresses provoke different myocardial ischemic responses. These observations suggest that exercise or adenosine testing may not adequately assess the likelihood of occurrence or severity of MSIMI and that different mechanisms are operative in each condition.

Association of 1 -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.

Usefulness of Peripheral Arterial Tonometry in the Detection of Mental Stress‐Induced Myocardial Ischemia

Mental stress‐induced myocardial ischemia (MSIMI) identifies a subset of coronary arterial disease (CAD) patients at increased risk for adverse cardiovascular events. Peripheral arterial vasoconstriction has been consistently reported as an underlying mechanism for ischemia development in this setting and as such affords a unique opportunity for the noninvasive detection of this phenomenon.

Do men and women differ on measures of mental stress-induced ischemia?

Objective: To consider the effects of gender on ischemia in a larger sample, with broadly defined coronary artery disease (CAD). Mental stress has been shown to cause transient myocardial ischemia in a significant percentage of people with CAD. However, little is known about the effects of mental stress on ischemic processes in women. Most studies to date either had few women or required a positive exercise stress test. Methods: Participants (61 women, 93 men; average age = 63 years) had documented CAD (positive stress test, abnormal catheterization even with minimal disease, or previous myocardial infarction). They underwent mental stress testing and radionuclide perfusion imaging (stress/ rest). Cardiac function data were collected and stress was compared with baseline. The data were then submitted to a series of analyses of variance. Results: A total of 50 (32%) participants exhibited reversible ischemia post psychological stress. This reflects a relative rate of 33% (n = 31of 93) for men and 31% (n = 19 of 61) for women. No difference between men and women were observed on any measure of hemodynamic functioning (blood pressure, heart rate, or cardiac perfusion). Conclusions: Results of this study showed no significant differences between men and women on measures of hemodynamic functioning or cardiac perfusion. ACE = angiotensin-converting enzyme; BMI = body mass index; CABG = coronary artery bypass graft; CAD = coronary artery disease; DBP = diastolic blood pressure; &Dgr; DBP = change in diastolic blood pressure; LVEF = left ventricular ejection fraction; HR = heart rate; &Dgr; HR = change in heart rate; MI = myocardial infarction; SBP = systolic blood pressure; &Dgr; SBP = change in systolic blood pressure; SDS = summed difference score; VAMS = Visual Analogue Mood Scale.