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ORIGINAL ARTICLES |
From Cardiovascular Research (K.M.Y., M.H., D.L., M.B., D.S.S.), Department of Medicine, University of Florida, Gainesville, Florida; North Florida/South Georgia VA Healthcare System (K.M.Y., M.H., D.L., M.B., D.S.S.), Gainesville, Florida; Department of Biostatistics (Q.L., H.L.), University of Florida, Gainesville, Florida; and Department of Community Dentistry and Behavioral Science (R.B.F.), College of Dentistry, University of Florida, Gainesville, Florida.
Address correspondence and reprint requests to Kaki M. York, PhD, Psychology Service (116B), 1601 SW Archer Rd, Gainesville, FL 32608. E-mail: kaki.york{at}va.gov
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ABSTRACT |
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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.
Key Words: gender • mental stress • myocardial ischemia • hemodynamic • single photon emission computed tomography
Abbreviations: ACE = angiotensin-converting enzyme; BMI = body mass index; CABG = coronary artery bypass graft; CAD = coronary artery disease; DBP = diastolic blood pressure; 
DBP = change in diastolic blood pressure; LVEF = left ventricular ejection fraction; HR = heart rate; HR = change in heart rate; MI = myocardial infarction; SBP = systolic blood pressure; SBP = change in systolic blood pressure; SDS = summed difference score; VAMS = Visual Analogue Mood Scale.
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INTRODUCTION |
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However, little is known about the effects of mental stress-induced ischemia in women. Many studies examining cardiovascular responses to mental stress have used only male participants (12–16). Previous studies which included both genders still had few women. For example, the Psychological Investigations of Myocardial Ischemia Study investigated the effects of mental stress on myocardial perfusion in 196 people with stable CAD (5). This study reported data from one of the largest known samples of women to date. However, only 13% (n = 25) of the participants were female (5). Other studies reported data from as few as two women (5,10,11). As there were so few women included in the previous samples, results were not examined separately for males and females. In their recent systematic review of the literature, Strike and Steptoe cited insufficient information about the effect of mental stress on women as one of the primary limitations of the current literature (17). A more recent study by Blumenthal and colleagues (18) included 42 women (approximately 31% of the sample). However, this was an interventional study and baseline frequency of abnormal response to mental stress procedures was not reported separately by gender. Furthermore, all of these studies required a positive exercise stress test before inclusion, although recent reports suggest that mental stress-induced ischemia also occurs in patients without exercise- or adenosine-induced ischemia (9,10). Therefore, the purpose of the current study was to consider the effect of mental stress and gender on myocardial perfusion in a larger sample with broadly defined CAD.
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METHODS |
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Design and Procedure
Before beginning this study, all participants were informed of their rights and responsibilities and briefed on the research protocol. They provided informed consent in accordance with the procedure approved by the University of Florida Institutional Review Board. All participants were tested in the morning after a 12-hour fast. Participants were also specifically asked to refrain from consuming caffeine. Anti-anginal medications were withheld for 24 hours before testing.
On the day of each study, participants reported to the laboratory and entered a cool, dark, and quiet room, where they were placed in a reclined position and asked to rest for 30 minutes during which time baseline hemodynamic data (heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure) were obtained. At the end of the 30-minute resting period, mental stress was induced via a public speaking task. Participants were given a brief description of a real-life hassle and were instructed to spend 2 minutes preparing their story. They were then asked to role play the events described in the scenario for 3 minutes. Participants were provided with a clock so that they could time their speech. They were told that their speech would be recorded and replayed later by the laboratory staff who would rate it for content, quality, and duration. Participants received a radioisotope injection intravenously at 1 minute into the speech. Hemodynamic data were also obtained at 1-minute intervals throughout the mental stress task and immediately after the speech. Peak stress values were compared with baseline levels in subsequent analyses.
The Visual Analogue Mood Scale (VAMS), a brief Likert type rating scale, was administered immediately before and after the mental stress procedure. For study purposes, VAMS was used to determine change in current emotion/activation ratings in response to the mental stress procedure.
Myocardial Perfusion Imaging
Technetium-99m Sestamibi was used in all radionuclide imaging procedures. On the day of the resting study, participants were brought to the laboratory and seated in cool, dark, quiet room where they were asked to rest for 30 minutes. The radionuclide was administered at the end of this rest period and images were obtained after adequate clearance, typically at least 45 minutes later. Similarly, stress study images were obtained approximately 45 minutes after completion of the mental stress procedure. Rest and stress images were either obtained on the same day or on another day within a week of each other.
Radionuclide images were analyzed by an experienced reader, blinded to condition, following guidelines established by the American Society for Nuclear Cardiology. Adequate quality of images was assured before interpretation. Processing of images was conducted (Philips Medical System JetStream Workstation, Philips Medical Systems North America, Bothell, Washington) using AutoSpect and AutoQuant version 6.0 software. The 20-segment model was utilized and reading was cross-referenced to QPS quantification of raw counts in a segmental grid as needed.
Rest and stress images were visually compared for number and severity of perfusion defects, using a scoring method from 0 to 4 (0 = normal uptake; 4 = no uptake). A summed difference score (SDS) was calculated as the difference between summed stress and rest scores. An abnormal score was defined as SDS 
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Statistical Analyses
Descriptive statistics (Table 1) were computed for all demographic characteristics of the sample. Mean and standard deviation values were obtained for all continuous variables and frequencies/ percentages were obtained for categorical variables. 
2 procedures were used to examine demographic differences on categorical variables. Analysis of variance (ANOVA) was used to test for potential differences on continuous variables. The difference between peak stress and baseline was calculated for all hemodynamic ( SBP, DBP, HR) and cardiac perfusion (SDS) variables. The data were submitted to a series of ANOVA with hemodynamic response as the dependent variable and gender as the independent variable. Covariate adjusted models controlled for the effects of disease severity, as indicated by number of vessels with at least 50% stenosis on angiogram, comorbidities (hypertension and diabetes), current medications (calcium-channel blockers, ß blockers, and angiotensin-converting enzyme (ACE) inhibitors), and smoking history. Statistical significance was determined using 
= 0.05.
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RESULTS |
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= 8.58). Participants had a number of comorbid conditions including hypertension (75%), hyperlipidemia (88%), and diabetes mellitus (29%). Participants were also taking a variety of cardiovascular medications (ß blockers, 75%; calcium-channel blockers, 21%; ACE inhibitors, 56%; and statins, 79%). However, these medications were withheld for 24 hours before testing. Additionally, 20% of participants reported that they were taking antidepressant medications at the time of this study. Antidepressants were not withheld before testing.
Statistically significant differences between male and female participants were observed on several baseline characteristics. Women were more likely to report current use of calcium- channel blockers (2 = 6.60, p = .01). Men were more likely to report tobacco use (2 = 13.96, p < .01) as well as current use of ß blockers (2 = 14.45, p < .01) and ACE inhibitors (2 = 4.05, p = .04). Men were more likely to report both former (2 = 9.72, p = .002) and current smoking (2 = 8.33, p = .004) than women. Men also had higher summed rest scores (F(1,152) = 13.80, p = .01) and lower baseline left ventricular LVEF (F(1,152) = 28.55, p < .01). However, no significant gender differences were observed for frequency of entry criteria (abnormal angiogram, abnormal nuclear stress test, abnormal exercise stress test, history of MI, history of CABG, history of percutaneous transluminal coronary angioplasty), or comorbid conditions (diabetes, hypertension, or hyperlipidemia).
Preliminary analyses revealed that approximately 32% (50 participants) of the sample exhibited significant myocardial ischemia in response to mental stress. When the sample was divided by gender, myocardial ischemia was observed in 33% (31) of male and 31% (19) of female participants, respectively. This difference was not statistically significant (2 = 0.08, p = .77).
Preliminary results also revealed significant increases in SBP, DBP, and HR from rest to stress. All changes were statistically significant at the p < .01 level (Tables 2 and 3).
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To test the primary hypothesis that there would be gender differences in hemodynamic variables and cardiac perfusion in response to mental stress, a series of ANOVAs were performed. The results of these analyses revealed no statistically significant differences between male and female participants on any measure of hemodynamic function. The mean change in SBP in mm Hg was 45 for males and 46 for females (F(1,160) = 0.02, p = .90) (Figure 1). The mean change in DBP in mm Hg was 29 for men and 30 for women (F(1, 160) = 0.10, p = .75) (Figure 1). The mean change in HR in beats/minute was 19 for men and 23 for women (F(1,160) = 3.38, p = .07) (Figure 1). Similarly, no significant differences between men and women were observed on a radionuclide imaging measure of cardiac perfusion (SDS (meanmale = 2.05, meanfemale = 2.04), F(1,160) = 0.00, p = .99) (Figure 1). Furthermore, a Wilcoxon test revealed no significant difference in SDS scores between genders (p = .27) within the 50 patients exhibiting mental stress-induced myocardial ischemia. Nor were there gender differences in hemodynamic function (SBP, p = .90; DBP, p = .21; HR, p = .50) within the mental stress positive group.
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Even after controlling for the effect of disease severity, comorbid conditions, current medications and smoking status, main effects for gender were not observed for either SBP (F(8,96) = 0.14, p = .71) or DBP (F(8,96) = 0.29, p = .59). Neither were gender effects observed for either HR (F(8, 96) = 0.28, p = .60) or SDS (F(8, 95) = 0.04, p = .86).
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DISCUSSION |
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The purpose of the current study was to consider the effects of gender on ischemia in a larger sample of men and women with broadly defined CAD, using perfusion imaging. A total of 154 people with CAD participated in this study. Approximately 34% (61 individuals) were women. This represents the largest known sample of women in this area of the literature to date. Results demonstrated significant differences between male and female participants on several baseline characteristics including current medications and tobacco use history. Despite these baseline differences, no statistically significant differences between male and female participants were observed on any measure of hemodynamic functioning or cardiac perfusion.
There are known differences between men and women in terms of clinical presentation of CAD (19), exercise stress results (20), and even pathological features of CAD (21). Studies suggest that women are likely to be older, with different comorbidities and treatment regimens (22). Exercise stress test results differ in men and women (20). It has also previously been shown that induction of mental stress via the Stroop Color Word Test and public speaking tasks may provoke different results in males and females (6,23). Therefore, it seemed reasonable to believe that men and women might differ in terms of mental stress-induced ischemia. However, the results of this study suggest that both the rate and frequency of MSI are comparable in men and women.
Furthermore, many previous studies that included female participants and examined the effects of mental stress on the heart used blood pool imaging techniques as opposed to the myocardial perfusion single photon emission computed tomography (SPECT) imaging procedure employed in the present study. This is problematic because even normal people without CAD can develop a drop in LVEF with mental stress (24). In contrast, we have shown that SPECT imaging has good sensitivity, specificity, and reproducibility for the detection of mental stress-induced ischemia (25) in both women and men and is probably superior to radionuclide ventriculography.
These results, nevertheless, should be interpreted cautiously. Through focused recruitment efforts, this study significantly increased the amount of information available on mental stress ischemia in women. However, the current study ultimately included only 61 women from a single site. To definitely determine whether or not men and women differ on measures of mental stress-induced ischemia, additional studies with larger numbers of women obtained from several sites across the country will be required.
It is also important to recognize that the mean age of participants in this study was similar for both men and women. Age-matched females would be expected to have less severe disease then their male counterparts. In this study, male participants had higher summed rest scores, suggesting they may have had higher initial disease severity. Nonetheless, results remained nonsignificant even after controlling for initial disease severity as indicated by number of vessels with at least 50% stenosis on angiogram. This suggests that it is unlikely that disease severity influenced the results of our study.
Furthermore, mental stress testing is still experimental in nature compared with exercise or chemical stress testing. Unlike the more commonly used clinical procedures, it is more difficult to measure the amount of stress administered during a mental stress procedure. However, HR and BP response may be used as one indicator of the degree of stress experienced. Subjective participant ratings of task engagement and immediate mood states may also provide some insight into the amount of stress administered. HR and BP measurements were included in this study and indicated that all patients experienced statistically significant increases in hemodynamics in response to the mental stress procedure. HR and BP response was comparable in both genders. Similarly, participant ratings of immediate mood state/activation also increased significantly from rest to stress in all patients. This effect was more pronounced in women, who tend to be more emotionally expressive (26), than in male participants. Whereas hemodynamic and mood state ratings are not as definite as the metabolic equivalent measure obtained during an exercise stress test, they do suggest that participants experienced a significant amount of stress.
In conclusion, the results of this study suggest that it is unlikely that men and women differ in either the frequency or severity of mental stress-induced ischemia as indicated by radionuclide perfusion imaging measures. Due to the known health risks associated with an ischemic response to mental stress in certain patients with CAD, it will be important for physicians to be aware that women are likely to experience mental stress-induced ischemia at the same rate as their male patients.
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NOTES |
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This study was supported by Grants HL 070265 and HL 072059 from the National Heart Lung and Blood Institute. This material is also the result of work supported with resources and the use of facilities at the Department of Veterans Affairs Medical Center, Gainesville, Florida.
Because co-author David S. Sheps is Editor-in-Chief of this journal, the review of this paper was overseen by a guest editor who was chosen by other editors of the journal. Dr. Sheps was not involved in the decision-making process and, like all authors, he was blinded to the identity of the peer reviewers.
DOI:10.1097/PSY.0b013e31815a9245
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