doi: 10.1161/hy1101.095009
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(Hypertension. 2001;38:997.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Gender Differences in Associations of Diurnal Blood Pressure Variation, Awake Physical Activity, and Sleep Quality With Negative Affect
The Work Site Blood Pressure Study
From the Zena and Michael A. Wiener Cardiovascular Center, Behavioral and Integrative Cardiology Program, Mount Sinai School of Medicine (K.K., K.W.D., T.G.P.), New York, NY; and the Department of Psychiatry, State University of New York (J.E.S.), Stony Brook.
Correspondence to Kazuomi Kario, MD, PhD, FACC, or Joseph E. Schwartz, PhD, Integrative and Behavioral Cardiology Program, Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, 50 East 98th St, Suite 1B, New York, NY 10029. E-mail kkario{at}jichi.ac.jp or jschwartz@mail.psychiatry.sunysb.edu
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Abstract |
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Abstract—— This study reports on the associations among depression, anxiety, awake physical activity, sleep quality (assessed by nocturnal physical activity), and diurnal blood pressure (BP) variation in a nonpsychiatric sample (The Work Site Blood Pressure Study). We conducted ambulatory BP (ABP) monitoring and actigraphy in 231 working men and women. Depression and anxiety were measured by the Brief Symptom Inventory. There were gender-specific associations between depression or anxiety and ABP parameters. In men, depression was associated positively with the sleep/awake systolic BP (SBP) ratio (r=0.24, P=0.006). After controlling for age, body mass index, and awake and sleep activity, depression remained significantly associated with the sleep/awake SBP ratio (r=0.25, P=0.005) and was also significantly related to sleep SBP (r=0.21, P=0.02). Anxiety, which was related to depression (r=0.73, P<0.0001), had a similar but slightly weaker pattern of associations with ABP and activity. These associations were not found in women, but there were associations of anxiety with awake SBP (r=0.24, P=0.01) and pulse rate (r=0.27, P=0.006). In conclusion, depression is associated with disrupted diurnal BP variation independent of ambulatory physical activity in working men, whereas anxiety is associated with awake SBP and pulse rate in women.
Key Words: blood pressure • blood pressure monitoring, ambulatory • gender
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Introduction |
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There is growing evidence that depression is one of the most important psychological predictors of cardiovascular disease.1 Depression and depressive symptoms are exceedingly common in the general population.2 A large epidemiological study of >18 500 persons reported the lifetime prevalence rate of subthreshold depressive symptoms to be 23%.3 Recent clinical studies have shown that depression and related conditions, such as anxiety, even at subthreshold levels, are independent predictors of hypertension and cardiovascular events (both coronary heart disease and stroke).1,3–8 In addition to activating the neuroendocrine system (sympathetic activity and hypothalamus-pituitary-adrenal [HPA] axis), major depression has also been reported to disrupt the diurnal rhythm of these neuroendocrine factors, which, in turn, are closely associated with blood pressure (BP).2,6
There are clear gender differences in the prevalence of depression and related disorders.9 Depressive symptoms and major depression are more common in women.9 On the other hand, cardiovascular events and hypertension are less frequent in women, particularly before menopause.10 Thus, the impact of depression on the cardiovascular system may be different between women and men.
Ambulatory BP (ABP) monitoring (ABPM) performed in healthy subjects has shown that BP levels typically decrease during sleep, by 10% to 20% of the mean awake BP.11 Several studies have recently found that an abnormal diurnal BP variation, characterized by diminished nocturnal BP dipping, is associated with silent and clinical cardiovascular disease.12–17 This diminished nocturnal BP dipping is hypothesized to be caused by various factors, including autonomic nervous system activity and the HPA axis.18–23 We have recently demonstrated that ambulatory physical activity, monitored by use of actigraphy, is one of the determinants of nocturnal BP dipping. An increase in nocturnal physical activity, which is sometimes used as an indicator of sleep quality,24 and a decrease in awake physical activity are associated with less dipping of BP.25 Major depression and anxiety are often characterized by poor sleep quality and altered physical activity levels,2,26,27 which might predict disruption of the diurnal BP variation and an increased risk of cardiovascular disease. However, the relationship between depression and diurnal BP variation in nonpsychiatric samples is not clear.
To study the gender-specific associations among depression and anxiety, awake physical activity, sleep quality (assessed by nocturnal physical activity), and diurnal BP variation, we analyzed ABPM and actigraphic data collected from 231working men and women enrolled in the Work Site Blood Pressure Study.18,21,22
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Methods |
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Subjects
We studied 126 men and 105 women age 30 to 66 years (mean±SD 46±8.9 years) (Table 1). The subjects for the present study were recruited as part of the larger Work Site Blood Pressure Study. The data reported herein were collected between 1992 and 1996, during the third assessment for those enrolled in the study from the initial 8 work sites, the second assessment for those enrolled from the ninth work site, and the initial assessment for those enrolled from the 10th work site. This study population has been described more fully elsewhere.22,25,28 Selection criteria for the present investigation included the following: (1) subjects were taking no medication for hypertension, depression, or anxiety; (2) subjects had completed the Brief Symptom Inventory (BSI); (3) subjects had completed actigraphic data; and (4) subjects had a minimum of 15 valid awake and 4 valid sleep BP readings. Shift workers were excluded from the present study. Depression and anxiety were assessed by the BSI,29 a shortened version of the SCL-90-R (Symptom Rating Checklist-90-Revised), which has 6 items for each scale. Response options range from 0 to 4 (ranging from "not at all" to "extremely"), and the scale score is the mean of the 6 items. The depression and anxiety scales were quite highly correlated (0.73 in men, 0.50 in women, and 0.62 in the total sample).
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24-Hour ABPM
Noninvasive ABPM was performed on a normal weekday with an automatic ABP monitor (SpaceLabs 90207), which was programmed to measure BP and heart rate every 15 minutes during the anticipated awake period and every 60 minutes during anticipated sleep. Sleep BP was defined as the mean BP from the time at which the participant went to bed until the time of awakening, and the awake BP was defined as the mean BP during the remaining portion of the day. The sleep/awake BP ratios were defined as the ratio of sleep BP to awake BP.
Assessment of Physical Activity by Actigraphy
Subjects wore an actigraph (Ambulatory Monitoring Inc) on the waist while they were awake and on the wrist during sleep. On the basis of preliminary analyses of the within-person relation of activity to awake ABP readings,25 a weighted average of activity during the 6-minute period before and including each BP measurement was used as the summary measure of current/recent physical activity that best predicts within-person fluctuations in ABP. Mean awake (sleep) activity was defined as the mean activity score of the 6-minute periods that corresponded to all awake (sleep) BP assessments. The square root transformation was applied to all activity measures to reduce the positive skew of the distribution and make it more normal.
Statistical Analysis
The Mann-Whitney U test was used to test the difference of the mean values between men and women, and the Spearman nonparametric rank order correlation and partial correlation coefficients were used to measure the relationships among continuous measures. ANCOVA was used to test the difference between men and women in the slope of the ranked sleep/awake systolic BP (SBP) ratios and depression scores.
An expanded Methods section can be found in an online data supplement available at http://www.hypertensionaha.org.
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Results |
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The mean levels of awake and sleep BPs were higher in men than in women: respective awake and sleep SBPs were 130 and 111 mm Hg for men and 119 and 104 mm Hg for women, and respective awake and sleep diastolic BPs (DBPs) were 84 and 76 mm Hg for men and 78 and 62 mm Hg for women (all P<0.001). The sleep/awake ratios were comparable between men and women (SBP, 0.86 versus 0.87, respectively; DBP, 0.80 versus 0.80, respectively). The average scores on depression tended to be higher for women (0.35 for men versus 0.44 for women, P=0.07), whereas average anxiety scores were comparable between men and women (0.44 versus 0.44, respectively; P=NS).
Correlations of Depression and Anxiety With ABP
In the full sample, anxiety was positively correlated with awake and sleep pulse rate (PR) and sleep SBP (Table 2). After controlling for age, body mass index (BMI), gender, and awake and sleep activity, the associations with awake and sleep PR remained significant (Table 3). Depression was not associated with any cardiovascular parameters in the total sample.
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Men
In the separate analysis for men and women, marked gender differences were observed. In men, the depression (r=0.24, P=0.006) and anxiety (r=0.20, P=0.02) scales were positively and significantly correlated with the sleep/awake SBP ratio. After controlling for age, BMI, and awake and sleep activity (Table 3), the associations of depression and anxiety with the sleep/awake SBP ratio remained significant (r=0.25, P=0.005, and r=0.19, P=0.03, respectively), and depression was correlated with sleep SBP (r=0.19, P=0.03).
ABP in the More Depressed Group of Men
We divided the 126 male subjects into a more depressed group (Q5, n=21) and a less depressed group (Q1–4, n=105) based on quintiles of the depression scale. Figure 1 shows the pattern of ABP and physical activity in men stratified by more depressed and less depressed groups. The sleep/awake SBP ratio was higher in the more depressed group than in the less depressed group (0.98 versus 0.85, respectively; P=0.005), although the differences in the numbers of those with no BP dipping (ie, those with sleep/awake SBP ratio >0.9) did not reach statistical significance (33% versus 21%, respectively; P=0.219). Sleep SBP tended to be higher in the more depressed group than in the less depressed group (115 versus 111 mm Hg, respectively; P=0.13). There were no significant differences in either the awake BPs or in the awake or sleep physical activity levels between the 2 groups. There were no significant differences between the more depressed and less depressed groups in duration of sleep time, based on ABP diary (6.6 versus 6.9 hours, respectively), or in sleep activity.
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In contrast, the degree of the nocturnal BP dipping was comparable between the more anxious (the Q5 of the anxiety scale) and less anxious (Q1–4) groups. We note that 62% of the more depressed group was also classified into the more anxious group.
Women
There were no significant associations between the depression scale and cardiovascular parameters. There was also not a significant difference in ABP between the more (Q5) and less (Q1–4) depressed groups (Figure 2). Consistent with this finding, the ANCOVA found that the slope of the sleep/awake BP ratio/depression relationship was significantly greater (P=0.007) for men than for women.
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In contrast, the anxiety scale was positively correlated with awake SBP (r=0.24, P=0.01) and PR (r=0.27, P=0.008) in women. These associations remained significant after controlling for age, BMI, and awake and sleep activity. Although physical activity in the evening was decreased in the more anxious group, the ABP and diurnal variation were comparable between the more (Q5) and less (Q1–4) anxious groups (Figure 2). The more anxious group compared with the less anxious group tended to have higher levels of awake SBP (121 versus 119 mm Hg, respectively; P=0.31) and PR (83 versus 80 bpm, respectively; P=0.19), but these differences did not approach statistical difference.
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Discussion |
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In the present study, we found gender-specific associations of ABP and its diurnal variation with negative-affect symptoms in a nonpsychiatric sample of working adult subjects who were normotensive or mildly hypertensive. In men, depression was associated with a diminished diurnal rhythm of BP, whereas in women, the mean awake SBP and PR were associated with anxiety symptomatology. In both men and women, these associations were independent of awake physical activity and sleep quality (assessed by actigraphy).
In a previous study involving the onset of acute myocardial infarctions, 53% of depressed patients, compared with 20% of nondepressed patients, reported an onset of symptoms between 10:00 PM and 6:00 AM In contrast, 48% of the nondepressed patients, compared with 20% of the depressed patients, reported an onset between 6:00 AM and 2:00 PM.30 It is possible that this difference in the time of onset between depressed and nondepressed patients is related to the difference in diurnal rhythm of BP found in the present study.
Gender-Specific Association Between Depressive Symptoms and Nocturnal BP Fall
In the present study, we found an association between depressive and anxiety symptoms and the sleep/awake ratio of BPs in men. In addition, this association was significantly greater for men than for women. It is possible that depression has a less deleterious effect on cardiovascular disease progression in women, although our review of the depression and heart disease literature indicates that few studies stratify their samples to examine gender differences. In a previous study that examined men and women separately, the association between depression status and cardiovascular events and related death was substantially greater in men than in women.31 In that study of 1003 community-dwelling persons, the relative risk of cardiovascular disease–related death in depressed (versus nondepressed) individuals was 2.5 for men and 1.5 for women. In another study of 5355 men and women age 45 to 77 years, the relative risk was 2.6 for men and 1.9 for women.32 The nondipping pattern of BP that we observed in depressed men has in several studies been related to a high cardiovascular morbidity,16 and it may be that if depressed women are less likely to show changes in the diurnal rhythm of BP than are men, this contributes to their lower risk of depression-associated cardiovascular morbidity. Additionally, menopause reduces the nocturnal BP fall in women,33 whereas hormone replacement therapy inhibits this reduction.34 Thus, estrogen may play a significant protective role against the effect of depression on nocturnal BP dipping.
Depression and Physical Activity
In previous studies using actigraphy, lower levels of daytime physical activity have been found to be directly related to the severity of depression, and increasing physical activity accurately mirrors recovery in patients with major depression.26,27 In addition, in symptomatic patients with major depression, the severity of depression is associated with greater nocturnal activity assessed by actigraphy and also poorer self-reported sleep quality.35 However, in the present study on a nonpsychiatric sample, there was no significant association between depressive symptoms and awake physical activity assessed by actigraphy. In addition, sleep activity, an indicator of sleep quality, was also not associated with depressive symptoms. These results may indicate that awake behavior and sleep quality are not changed until depression becomes sufficiently severe to be clinically overt. Otherwise, they may not act as mediators of the effect of subclinical depression on cardiovascular functioning/disease.
Mechanism of the Association Between Depression and Nocturnal BP Fall
The positive association between depression and the sleep/awake SBP ratio in men was significant even after controlling for age, BMI, and physical activity. In addition, the depression scale tended to be positively associated with sleep SBP, and after controlling for the above factors, this association became statistically significant. Thus, in contrast to the changes in physical activity and sleep quality, the nocturnal nondipping BP pattern may be more closely related to the pathophysiology of depression. These results may indicate that there are factors other than physical activity and sleep quality that mediate the association between depression and nocturnal BP dipping. Depression is thought to disrupt autonomic balance (especially to increase sympathetic activity and decrease parasympathetic activity) and to activate the HPA axis.1,6 These neurohormonal factors might be possible mediators of the association between depression and less nocturnal BP dipping. Both abnormal autonomic nervous system activity and increased HPA axis are associated with diminished nocturnal BP fall.18,20,21 Because estrogen is known to weaken the effects of these mediators on target organs,1 this might explain why the positive association between depressive symptoms and nondipping of nocturnal BP is only found in men.
Depression Versus Anxiety on Nocturnal BP Fall in Men
The depression and anxiety symptom subscales are highly correlated measures of negative affect. When depression and anxiety were included in the same multiple linear regression model, the sleep/awake SBP ratio (dependent variable) remained independently associated with the depression scale (standardized ß coefficient=0.219, P=0.08), whereas the association with anxiety disappeared. Although it is difficult to separate completely these 2 constructs, this result suggests that it is the depressive symptoms that impact nocturnal BP dipping.
Association Between Anxiety Symptoms and Ambulatory BP and PR in Women
There was a positive association of anxiety with awake SBP and PR. After controlling for awake and sleep activity, the association with awake SBP and PR remained significant. Anxiety may be associated with short-term sympathetic activation predominantly during the awake period, but this effect may not persist throughout a 24-hour period, leading to elevated PR. This effect was significant only in women. Furthermore, anxiety was not associated with nondipping in women. This is consistent with previous reports of gender differences in hemodynamic response patterns to behavioral stressors. In 1 study, women exhibited significantly greater cardiac output increase during a psychological stress task, whereas men tended to respond with greater increases in total peripheral resistance.36
Study Limitations
The magnitude of the associations between psychological factors and ABP were relatively small, even in this well-defined nonpsychiatric sample in which standardized 24-hour ABP and actigraphy data were collected. This might be due to the following limitations of the present study.
The BSI used to assess depressive and anxiety symptoms includes only 6 items for each scale, selected from the 10 items used in the SCL-90-R. Although a longer questionnaire would probably yield scores with better psychometric properties, an analysis of SCL-90-R data collected in the first 2 assessments (1985 to 1991) of the Work Site Blood Pressure Study reveal that in this nonclinical sample, the correlation between the total score calculated from all 10 items and the score calculated from the 6 items included in the BSI is good: 0.784 for depression and 0.891 for anxiety.
Another potential limitation is the healthy nature of our study sample of working individuals. Few, if any, individuals in the present study would meet criteria for a clinical diagnosis of major depression or an anxiety disorder. Thus, in contrast to much of the literature cited above, the relationships reported herein exist within the normal (ie, nonclinical) range of negative affect symptomatology. The present study, although probably more representative of the general population than a clinic sample, may have less variance of the psychological measures, which would tend to attenuate (relative to clinical samples) the estimated strength of the associations with the cardiovascular measures.
Conclusions
Depression is associated with disrupted diurnal BP variation independent of awake physical activity and sleep quality in working men, whereas anxiety is associated with awake BP and PR in working women. The effect of depression on ABP and its diurnal variation may not be mediated by physical activity and sleep quality in subclinical depression and may precede changes in these behavioral factors.
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Acknowledgments |
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This study was supported in part by grant HL-47540 from the National Heart, Lung, and Blood Institute and by grants in-aid (1992–1999) from the Foundation for the Development of the Community, Tochigi, Japan.
Received November 9, 2000; first decision February 1, 2001; accepted May 14, 2001.
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