Richard Nelesen - Academia.edu (original) (raw)
Papers by Richard Nelesen
Hypertension, Aug 1, 1992
There is considerable interest in blood pressure reactivity to psychological stressors. Because t... more There is considerable interest in blood pressure reactivity to psychological stressors. Because the sympathetic nervous system and the renin-angiotensln system are so responsive to stressors and are themselves the targets of many antihypertensive medications, many investigators have wondered if such medications decrease the blood pressure response to stressful stimuli. We studied 25 normotensive and 21 hypertensive men in a double-blind crossover study during which they received either placebo for 4 days or captopril (25 mg b.i.d.) for 4 days while they were hospitalized in a clinical research center. Patients were studied at resting baseline, while performing a mathematics task, and while reading out loud a disturbing newspaper article. Although captopril lowered the resting blood pressure levels, it had no effect on the amplitude of reactivity to stressors.
Psychosomatic Medicine, 1998
Psychosomatic Medicine, 1999
Springer eBooks, 1986
Anger is commonly believed to be involved in the development of hypertension, atherosclerosis, co... more Anger is commonly believed to be involved in the development of hypertension, atherosclerosis, coronary heart disease (CHD), and sudden cardiac death. In contrast, a program of moderate, sustained aerobic exercise is thought to retard this development. The paradox is that both the expression of anger and aerobic exercise are both known to elicit enhanced sympathetic nervous system (SNS) and cardiovascular activity. Therefore, in the present chapter we shall review the evidence that anger/hostility and aerobic activity can modulate autonomic functions and/or cardiovascular disease. We shall also discuss some of the biobehavioral variables associated with anger and hostility that might contribute towards cardiovascular disorders and explore some of the variables associated with aerobic activity that might improve cardiovascular functioning and/or retard cardiovascular disease processes.
Psychophysiology, Mar 1, 1993
This study examined the test‐retest reliability of task‐induced responses of blood pressure, hear... more This study examined the test‐retest reliability of task‐induced responses of blood pressure, heart rate, norepinephrine, epinephrine, anger, and anxiety in 98 black and white normotensive and hypertensive individuals. Subjects completed three laboratory tasks (standing, mental arithmetic, and cold pressor) on two occasions 10 days apart. For all subjects, all baseline and test‐retest correlation coefficients were significant (rs = .23–.71; median = .58). Baseline‐adjusted (residual scores) reactivity test‐retest correlation coefficients were consistently smaller (rs = .02–.55; median = .36). In contrast to the white hypertensives, white normotensives, and black normotensives, the black hypertensives showed no significant baseline‐adjusted test‐retest correlation coefficients (rs =−.21–.40; median = .12). Epinephrine responses revealed a significant session by race interaction; blacks had 20% higher mean values and whites had 10% lower mean values upon retesting. The data suggest that race and hypertension may interact to affect the temporal stability of task‐induced responses to stressors.
Journal of Hypertension, Aug 1, 2001
Objective Obstructive sleep apnea (OSA) is associated with increased prevalence of atheroscleroti... more Objective Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. Design Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32±64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classi®ed as having hypertension. Three hypercoagulability markers were measured: thrombin/ antithrombin III complex (TAT), ®brin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). Results Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n 19), (2) normotensive apneics (n 38), (3) hypertensive non-apneics (n 11), and (4) hypertensive apneics (n 19). OSA (groups 2 and 4) had no signi®cant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59±188 versus 77/53±108 pmol/l; P 0.009) and of DD (376/265±721 versus 303/190±490 ng/ml; P 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only signi®cant predictor of TAT (P 0.001) and of DD (P 0.004), whereas DBP was the only signi®cant predictor of vWF:ag (P 0.029). These ®ndings persisted even after controlling for gender, age, body mass index, RDI, mean S a O 2 , and hematocrit. Conclusion Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.
Metabolism-clinical and Experimental, Dec 1, 2001
Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increa... more Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance.
Fertility and Sterility, Feb 1, 2004
The impact of body fat distribution on cardiovascular hemodynamics in postmenopausal women is not... more The impact of body fat distribution on cardiovascular hemodynamics in postmenopausal women is not clear. In a sample of healthy postmenopausal women, greater central body fat distribution was associated with higher peripheral resistance, triglycerides, and total cholesterol as well as lower cardiac and stroke indexes.
Blood Pressure Monitoring, Apr 1, 2003
Objective Controversies surrounding the physiological effects of hormone replacement therapy (HRT... more Objective Controversies surrounding the physiological effects of hormone replacement therapy (HRT) currently lie at the forefront of medicine. Important interindividual factors that affect blood pressure, such as smoking, body mass and sodium intake, may account for the conflicting findings seen in studies examining the effects of HRT on blood pressure. Design The study was a randomized, double-blind, placebo-controlled trial. Methods The effect of combination HRT and estrogen-only replacement therapy (ERT) on ambulatory blood pressure was examined in a sample of 46 healthy, normotensive, non-smoking, non-obese postmenopausal women between 45 and 65 years of age. Twenty-four hour urinary sodium excretion was examined prior to and following treatment. The women were randomized to 3 months' treatment with HRT, ERT or placebo. Results After treatment, there were no significant effects of either HRT or ERT on daytime or night-time systolic or diastolic blood pressure. Sodium excretion was similar across the groups. There were no effects of treatment on night-time blood pressure dipping. Conclusions The findings from this prospective treatment study support the conclusion that HRT has no significant effect on daytime or night-time blood pressure in a sample of healthy, non-smoking postmenopausal women. Blood Press Monit 8:57-61 c 2003 Lippincott Williams & Wilkins.
Psychophysiology, 1999
Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to ... more Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to evaluate the ability of impedance cardiography (IC) to track the rapid hemodynamic (HD) changes elicited by these drugs. The AN response was measured after inhalation and the PE response was measured after a bolus injection in 19 subjects on two occasions. High reliability was observed for all of the HD measures. Blood pressure (BP), peripheral resistance (PR), and preejection period (PEP) decreased significantly after administration of AN, whereas heart rate (HR) and cardiac output (dotted Q) increased. BP and total PR increased significantly after administration of PE; HR and dotted Q decreased and PEP did not change significantly. Stroke volume did not change significantly with either drug. The BR slope was reliably elicited with AN and PE. The IC and Finapres BP consistently detected short‐term changes in HD responses to AN and PE. The pharmacological interventions demonstrated that IC measures followed the course predicted by the actions of the drugs. Change in PEP and dZ/dt reflected increased contractility. The BR sensitivity was also reproducible.
Sleep, Mar 1, 1996
Adrenergic regulation in sleep apnea is a complex process because adrenergic physiology is diffic... more Adrenergic regulation in sleep apnea is a complex process because adrenergic physiology is difficult to summarize with one measure. Furthermore, the role of the adrenergic system in sleep apnea is often confounded with hypertension, making interpretation difficult in hypertensive apneics. Sixty-six people with and without apnea and/or hypertension (all were off antihypertensive medication) participated in this study. Cardiac [3-adrenergic drive, as assessed by systolic time intervals, was examined at rest and in response to a mild laboratory stressor. These measures of cardiac contractility included the pre-ejection period, electrical systole (QT) interval and the cardiac acceleration index. At rest, apneics showed elevated myocardial contractility on all measures (p = 0.001). In response to the laboratory stressor, non-apneics showed an increase in cardiac [3-adrenergic drive (p = 0.001), whereas the contractility in apneics did not change or decreased relative to baseline. These findings suggest disrupted cardiac adrenergic regulation in people with sleep apnea. Apnea appears to increase resting sympathetic activity and down regulate [32-adrenergic receptors. The downregulation of cardiac [3-adrenergic receptor activity may explain the inability of people with sleep apnea to respond with appropriate cardiac contractility to a mild perturbation.
Hypertension, Apr 1, 1996
This study examined cardiovascular and catecholamine responses to two standardized laboratory str... more This study examined cardiovascular and catecholamine responses to two standardized laboratory stressors in 33 healthy age- and weight-matched black and white normotensive women (mean age, 32 years) during two phases of the menstrual cycle. Subjects were studied in a randomized order at the same time of day on two separate occasions approximately 6 weeks apart, once during the follicular phase (days 7 to 10 after menses) and once during the luteal phase (days 7 to 10 after the leutenizing hormone surge) of the menstrual cycle. Black women had higher systolic ( P =.01) and diastolic ( P =.01) pressures compared with white women. Black women showed greater diastolic pressure ( P <.01) and plasma epinephrine ( P <.05) responses to stress during the follicular compared with the luteal phase of the menstrual cycle; white women showed no significant changes in these variables. The findings extend the literature on race differences in responsivity to stress and indicate that in contrast to white women, reproductive hormones do influence cardiovascular and catecholamine responsivity to stress in black women.
Annals of Behavioral Medicine, Oct 1, 2003
Cardiovascular disease is the leading killer of women in developed countries. Menopause, stress, ... more Cardiovascular disease is the leading killer of women in developed countries. Menopause, stress, and lack of social support may contribute to the increased risk of heart disease morbidity and mortality in women. This study examined the effects of psychological stress and social support on autonomic nervous system control of the heart in 18 pre-and 34 postmenopausal women. Autonomic activity, as indexed by high-frequency heart rate variability and pre-ejection period, was assessed at rest and during a public speech task. Social support was determined using the Berkman Social Support Inventory. Postmenopausal women had higher heart rate (F = 4.4, p ≤ .04) and less parasympathetic activity (F = 11.9, p ≤ .001) compared with premenopausal women at rest. In response to stress, sympathetic nervous system activity increased in postmemopausal women (F = 6.1, p ≤ .02); however, this effect was no longer significant when age was used as a covariate in the analysis. Social support did not significantly affect measures of autonomic activity in either the pre-or postmenopausal women. Postmenopausal women have greater sympathetic and less parasympathetic activity than premenopausal women, which may account for their increased risk of coronary artery disease.
Blood Pressure Monitoring, Aug 1, 2000
Background Increasing evidence documents the fact that individuals whose blood pressure drops or ... more Background Increasing evidence documents the fact that individuals whose blood pressure drops or 'dips' relatively little at night have a higher risk of numerous cardiovascular illnesses. Objective To examine the reliability of various measures of nocturnal blood pressure dipping. Methods This study examined 17 individuals with ambulatory blood pressure monitoring on three 24 h recordings while they pursued a schedule similar to that of in-patients on a clinical research unit. Nocturnal dipping of blood pressure was scored three ways: as the drop in blood pressure between 10 p.m. and 6 a.m. () 'clocktime' , as the drop in blood pressure tailored to () each individual's reported bedtime 'bedtime' , and as the drop in blood pressure accompanying () polysomnographically verified sleep 'sleeptime'. Results Adequate reliability was obtained for all three measures of dipping. There was, in general, a significant () correlation across testing occasions P-0.05. The correlation coefficient ranged from 0.5 to 0.8, depending on which criterion of dipping was selected and whether the endpoint was systolic blood pressure, diastolic blood pressure, or mean arterial blood pressure. Conclusions The reliability of systolic blood pressure dipping was somewhat lower than that of diastolic or mean arterial blood pressure dipping. Dipping appears to be a reliable construct. While no one definition of dipping was demonstrably better than another, the most sensible definition of dipping would allow some adjustment for defining 'night' on the basis of each individual's idiosyncratic bed time.
American Journal of Obstetrics and Gynecology, May 1, 2002
This study examined the effects of oral estrogen (ERT) alone versus oral estrogen/medroxyprogeste... more This study examined the effects of oral estrogen (ERT) alone versus oral estrogen/medroxyprogesterone acetate (HRT) therapy on cardiovascular function, as controlled by the autonomic nervous system. Forty-three postmenopausal women received ERT, HRT, or a placebo for 3 months in a double-blind, randomized, placebo-controlled study. Cardiovascular hemodynamics and heart rate variability were assessed at rest and during stress. After 3 months of therapy, oral HRT significantly increased high-frequency power (P =.0002) and decreased total peripheral resistance (P =.04). The changes were evident at rest and during stress. Our findings suggest that combination therapy produces a more favorable alteration of autonomic cardiovascular function than estrogen alone (ie, combination therapy increases vagal activity).
Chest, Apr 1, 2001
We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on... more We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on cardiac contractility, heart rate variability, and hemodynamics at rest and in response to a laboratory stressor. Subjects and instrumentation: Forty-one apneic patients were studied on three occasions: before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP treatment. The subjects were randomly assigned to receive effective treatment or placebo. Contractility and hemodynamics were determined with impedance cardiography, and parasympathetic activity was assessed by analysis of heart rate variability. Measures were determined at rest and in response to a stressor. Design and results: For the cardiac sympathetic (contractility) measures (preejection period, cardiac acceleration index [CAI], and low-frequency/high-frequency ratio) significant interactions were found in the combination treatment (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline, preparation, talking) [p < 0.01]. For these measures, there were no differences between the treatment groups or responses to the stressor on day 1. Levels in placebo-treated subjects did not change or respond on the subsequent study days. In the CPAP-treated subjects, there was a decrease in these indexes at baseline, which became significantly lower by day 11 (ie, CAI levels were 24 ⍀/s 2 , 22 ⍀/s 2 , and 14 ⍀/s 2 on day 1, day 3, and day 11, respectively). These measures also became responsive to the stressor by showing increased sympathetic activity (CAI levels on day 11 were 14 ⍀/s 2 at baseline, 32 ⍀/s 2 during speech preparation, and 36 ⍀/s 2 while speaking). The parasympathetic indexes, such as high-frequency power or band of heart rate variability as determined by spectral analysis, showed a significant day-by-treatment interaction (p < 0.005), whereas the CPAPtreated group had significantly more parasympathetic activity after 1 week of treatment. For the hemodynamic measures (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]), there were significant treatment-by-study day-by-test-period interactions (p < 0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP-treated patients. Conclusions: These results indicate that CPAP normalizes contractility, increases cardiac vagal tone, and changes hemodynamic regulation from being resistance dominated to being cardiac dominated. Thus, after 1 week of treatment with CPAP, many of the indicators of poor cardiac functioning in apnea patients are improved.
Annals of Behavioral Medicine, Feb 1, 2001
Objective: This exploratory study investigated the relation between psychological mood states and... more Objective: This exploratory study investigated the relation between psychological mood states and hemodynamic variables obtained at rest. Methods: We measured resting hemodynamic variables using impedance cardiography, blood pressure, heart rate, and the Profile of Mood States (POMS) in 71 participants. Results: Mood states were not significantly associated with heart rate, systolic, diastolic, or mean arterial pressure. In comparison with these basic measures of physiology, a number of impedance derived measures of hemodynamics were associated with mood states. Log stroke volume was negatively correlated with POMS tension-anxiety (r =-.319, p = .009) and fatigue-inertia (r =-.316, p = .009). Log cardiac output was negatively associated with fatigue-inertia (r =-.346, p < .01). Log total peripheral vascular resistance was positively correlated with POMS fatigue-inertia (r = .276, p = .024). Conclusions: Our findings suggest that mood states are associated with hemodynamic variables underlying blood pressure.
Sleep and Breathing, Nov 7, 2006
Sleep, Mar 1, 1997
Patients with obstructive sleep apnea (OSA) are often hypertensive, and both apneics and hyperten... more Patients with obstructive sleep apnea (OSA) are often hypertensive, and both apneics and hypertensives are reported to have increased sympathetic nerve activity. We measured plasma norepinephrine (NE) levels, clearance, and release rate among 65 subjects who breathed room air, a hypoxic gas mixture, and the hypoxic mixture combined with intermittent breath holding. Apneics' plasma NE across all three breathing conditions was 307 pg/ml compared with the non-apneics' level of 248 pg/ml (p = 0.017). NE clearance increased from 3.2 IIminute to 3.9 IIminute when subjects breathed a hypoxic gas mixture (p < 0.001). NE clearance was similar among normal controls, apneics, and hypertensives. The rate at which NE was released from sympathetic nerves into the bloodstream was higher among hypertensives but not among apneics while subjects breathed room air. Hypoxia increased the NE-release rate from 892 ng/minute to 1,042 ng/minute (p < 0.001) and increased the NE-release rate more among apneics than non-apneics (p < 0.001). The NE-re1ease rate response to hypoxia and hreath holding differed between hypertensives and normotensives (p < 0.001) and between apneics and non-apneics (p < 0.001). Normotensive apneics had the largest increase in NE release during hypoxia. Like other investigators, we found that plasma NE levels were increased among apneics. Calculation ofNE-release rate and correction for blood pressure status revealed a more complex situation. Apneics breathing room air had a normal NE-release rate; any increase in sympathetic neuronal NE release could be attributed to apneics who were also hypertensive. However, apneics had a greater NE response to hypoxia. These results suggest that apneics are susceptible to transient increases in sympathetic nervous activity and that hypertensive apneics maintain increased sympathetic nervous release of NE in the daytime.
Psychosomatic Medicine, 1999
Hypertension, Aug 1, 1992
There is considerable interest in blood pressure reactivity to psychological stressors. Because t... more There is considerable interest in blood pressure reactivity to psychological stressors. Because the sympathetic nervous system and the renin-angiotensln system are so responsive to stressors and are themselves the targets of many antihypertensive medications, many investigators have wondered if such medications decrease the blood pressure response to stressful stimuli. We studied 25 normotensive and 21 hypertensive men in a double-blind crossover study during which they received either placebo for 4 days or captopril (25 mg b.i.d.) for 4 days while they were hospitalized in a clinical research center. Patients were studied at resting baseline, while performing a mathematics task, and while reading out loud a disturbing newspaper article. Although captopril lowered the resting blood pressure levels, it had no effect on the amplitude of reactivity to stressors.
Psychosomatic Medicine, 1998
Psychosomatic Medicine, 1999
Springer eBooks, 1986
Anger is commonly believed to be involved in the development of hypertension, atherosclerosis, co... more Anger is commonly believed to be involved in the development of hypertension, atherosclerosis, coronary heart disease (CHD), and sudden cardiac death. In contrast, a program of moderate, sustained aerobic exercise is thought to retard this development. The paradox is that both the expression of anger and aerobic exercise are both known to elicit enhanced sympathetic nervous system (SNS) and cardiovascular activity. Therefore, in the present chapter we shall review the evidence that anger/hostility and aerobic activity can modulate autonomic functions and/or cardiovascular disease. We shall also discuss some of the biobehavioral variables associated with anger and hostility that might contribute towards cardiovascular disorders and explore some of the variables associated with aerobic activity that might improve cardiovascular functioning and/or retard cardiovascular disease processes.
Psychophysiology, Mar 1, 1993
This study examined the test‐retest reliability of task‐induced responses of blood pressure, hear... more This study examined the test‐retest reliability of task‐induced responses of blood pressure, heart rate, norepinephrine, epinephrine, anger, and anxiety in 98 black and white normotensive and hypertensive individuals. Subjects completed three laboratory tasks (standing, mental arithmetic, and cold pressor) on two occasions 10 days apart. For all subjects, all baseline and test‐retest correlation coefficients were significant (rs = .23–.71; median = .58). Baseline‐adjusted (residual scores) reactivity test‐retest correlation coefficients were consistently smaller (rs = .02–.55; median = .36). In contrast to the white hypertensives, white normotensives, and black normotensives, the black hypertensives showed no significant baseline‐adjusted test‐retest correlation coefficients (rs =−.21–.40; median = .12). Epinephrine responses revealed a significant session by race interaction; blacks had 20% higher mean values and whites had 10% lower mean values upon retesting. The data suggest that race and hypertension may interact to affect the temporal stability of task‐induced responses to stressors.
Journal of Hypertension, Aug 1, 2001
Objective Obstructive sleep apnea (OSA) is associated with increased prevalence of atheroscleroti... more Objective Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. Design Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32±64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classi®ed as having hypertension. Three hypercoagulability markers were measured: thrombin/ antithrombin III complex (TAT), ®brin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). Results Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n 19), (2) normotensive apneics (n 38), (3) hypertensive non-apneics (n 11), and (4) hypertensive apneics (n 19). OSA (groups 2 and 4) had no signi®cant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59±188 versus 77/53±108 pmol/l; P 0.009) and of DD (376/265±721 versus 303/190±490 ng/ml; P 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only signi®cant predictor of TAT (P 0.001) and of DD (P 0.004), whereas DBP was the only signi®cant predictor of vWF:ag (P 0.029). These ®ndings persisted even after controlling for gender, age, body mass index, RDI, mean S a O 2 , and hematocrit. Conclusion Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.
Metabolism-clinical and Experimental, Dec 1, 2001
Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increa... more Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance.
Fertility and Sterility, Feb 1, 2004
The impact of body fat distribution on cardiovascular hemodynamics in postmenopausal women is not... more The impact of body fat distribution on cardiovascular hemodynamics in postmenopausal women is not clear. In a sample of healthy postmenopausal women, greater central body fat distribution was associated with higher peripheral resistance, triglycerides, and total cholesterol as well as lower cardiac and stroke indexes.
Blood Pressure Monitoring, Apr 1, 2003
Objective Controversies surrounding the physiological effects of hormone replacement therapy (HRT... more Objective Controversies surrounding the physiological effects of hormone replacement therapy (HRT) currently lie at the forefront of medicine. Important interindividual factors that affect blood pressure, such as smoking, body mass and sodium intake, may account for the conflicting findings seen in studies examining the effects of HRT on blood pressure. Design The study was a randomized, double-blind, placebo-controlled trial. Methods The effect of combination HRT and estrogen-only replacement therapy (ERT) on ambulatory blood pressure was examined in a sample of 46 healthy, normotensive, non-smoking, non-obese postmenopausal women between 45 and 65 years of age. Twenty-four hour urinary sodium excretion was examined prior to and following treatment. The women were randomized to 3 months' treatment with HRT, ERT or placebo. Results After treatment, there were no significant effects of either HRT or ERT on daytime or night-time systolic or diastolic blood pressure. Sodium excretion was similar across the groups. There were no effects of treatment on night-time blood pressure dipping. Conclusions The findings from this prospective treatment study support the conclusion that HRT has no significant effect on daytime or night-time blood pressure in a sample of healthy, non-smoking postmenopausal women. Blood Press Monit 8:57-61 c 2003 Lippincott Williams & Wilkins.
Psychophysiology, 1999
Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to ... more Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to evaluate the ability of impedance cardiography (IC) to track the rapid hemodynamic (HD) changes elicited by these drugs. The AN response was measured after inhalation and the PE response was measured after a bolus injection in 19 subjects on two occasions. High reliability was observed for all of the HD measures. Blood pressure (BP), peripheral resistance (PR), and preejection period (PEP) decreased significantly after administration of AN, whereas heart rate (HR) and cardiac output (dotted Q) increased. BP and total PR increased significantly after administration of PE; HR and dotted Q decreased and PEP did not change significantly. Stroke volume did not change significantly with either drug. The BR slope was reliably elicited with AN and PE. The IC and Finapres BP consistently detected short‐term changes in HD responses to AN and PE. The pharmacological interventions demonstrated that IC measures followed the course predicted by the actions of the drugs. Change in PEP and dZ/dt reflected increased contractility. The BR sensitivity was also reproducible.
Sleep, Mar 1, 1996
Adrenergic regulation in sleep apnea is a complex process because adrenergic physiology is diffic... more Adrenergic regulation in sleep apnea is a complex process because adrenergic physiology is difficult to summarize with one measure. Furthermore, the role of the adrenergic system in sleep apnea is often confounded with hypertension, making interpretation difficult in hypertensive apneics. Sixty-six people with and without apnea and/or hypertension (all were off antihypertensive medication) participated in this study. Cardiac [3-adrenergic drive, as assessed by systolic time intervals, was examined at rest and in response to a mild laboratory stressor. These measures of cardiac contractility included the pre-ejection period, electrical systole (QT) interval and the cardiac acceleration index. At rest, apneics showed elevated myocardial contractility on all measures (p = 0.001). In response to the laboratory stressor, non-apneics showed an increase in cardiac [3-adrenergic drive (p = 0.001), whereas the contractility in apneics did not change or decreased relative to baseline. These findings suggest disrupted cardiac adrenergic regulation in people with sleep apnea. Apnea appears to increase resting sympathetic activity and down regulate [32-adrenergic receptors. The downregulation of cardiac [3-adrenergic receptor activity may explain the inability of people with sleep apnea to respond with appropriate cardiac contractility to a mild perturbation.
Hypertension, Apr 1, 1996
This study examined cardiovascular and catecholamine responses to two standardized laboratory str... more This study examined cardiovascular and catecholamine responses to two standardized laboratory stressors in 33 healthy age- and weight-matched black and white normotensive women (mean age, 32 years) during two phases of the menstrual cycle. Subjects were studied in a randomized order at the same time of day on two separate occasions approximately 6 weeks apart, once during the follicular phase (days 7 to 10 after menses) and once during the luteal phase (days 7 to 10 after the leutenizing hormone surge) of the menstrual cycle. Black women had higher systolic ( P =.01) and diastolic ( P =.01) pressures compared with white women. Black women showed greater diastolic pressure ( P <.01) and plasma epinephrine ( P <.05) responses to stress during the follicular compared with the luteal phase of the menstrual cycle; white women showed no significant changes in these variables. The findings extend the literature on race differences in responsivity to stress and indicate that in contrast to white women, reproductive hormones do influence cardiovascular and catecholamine responsivity to stress in black women.
Annals of Behavioral Medicine, Oct 1, 2003
Cardiovascular disease is the leading killer of women in developed countries. Menopause, stress, ... more Cardiovascular disease is the leading killer of women in developed countries. Menopause, stress, and lack of social support may contribute to the increased risk of heart disease morbidity and mortality in women. This study examined the effects of psychological stress and social support on autonomic nervous system control of the heart in 18 pre-and 34 postmenopausal women. Autonomic activity, as indexed by high-frequency heart rate variability and pre-ejection period, was assessed at rest and during a public speech task. Social support was determined using the Berkman Social Support Inventory. Postmenopausal women had higher heart rate (F = 4.4, p ≤ .04) and less parasympathetic activity (F = 11.9, p ≤ .001) compared with premenopausal women at rest. In response to stress, sympathetic nervous system activity increased in postmemopausal women (F = 6.1, p ≤ .02); however, this effect was no longer significant when age was used as a covariate in the analysis. Social support did not significantly affect measures of autonomic activity in either the pre-or postmenopausal women. Postmenopausal women have greater sympathetic and less parasympathetic activity than premenopausal women, which may account for their increased risk of coronary artery disease.
Blood Pressure Monitoring, Aug 1, 2000
Background Increasing evidence documents the fact that individuals whose blood pressure drops or ... more Background Increasing evidence documents the fact that individuals whose blood pressure drops or 'dips' relatively little at night have a higher risk of numerous cardiovascular illnesses. Objective To examine the reliability of various measures of nocturnal blood pressure dipping. Methods This study examined 17 individuals with ambulatory blood pressure monitoring on three 24 h recordings while they pursued a schedule similar to that of in-patients on a clinical research unit. Nocturnal dipping of blood pressure was scored three ways: as the drop in blood pressure between 10 p.m. and 6 a.m. () 'clocktime' , as the drop in blood pressure tailored to () each individual's reported bedtime 'bedtime' , and as the drop in blood pressure accompanying () polysomnographically verified sleep 'sleeptime'. Results Adequate reliability was obtained for all three measures of dipping. There was, in general, a significant () correlation across testing occasions P-0.05. The correlation coefficient ranged from 0.5 to 0.8, depending on which criterion of dipping was selected and whether the endpoint was systolic blood pressure, diastolic blood pressure, or mean arterial blood pressure. Conclusions The reliability of systolic blood pressure dipping was somewhat lower than that of diastolic or mean arterial blood pressure dipping. Dipping appears to be a reliable construct. While no one definition of dipping was demonstrably better than another, the most sensible definition of dipping would allow some adjustment for defining 'night' on the basis of each individual's idiosyncratic bed time.
American Journal of Obstetrics and Gynecology, May 1, 2002
This study examined the effects of oral estrogen (ERT) alone versus oral estrogen/medroxyprogeste... more This study examined the effects of oral estrogen (ERT) alone versus oral estrogen/medroxyprogesterone acetate (HRT) therapy on cardiovascular function, as controlled by the autonomic nervous system. Forty-three postmenopausal women received ERT, HRT, or a placebo for 3 months in a double-blind, randomized, placebo-controlled study. Cardiovascular hemodynamics and heart rate variability were assessed at rest and during stress. After 3 months of therapy, oral HRT significantly increased high-frequency power (P =.0002) and decreased total peripheral resistance (P =.04). The changes were evident at rest and during stress. Our findings suggest that combination therapy produces a more favorable alteration of autonomic cardiovascular function than estrogen alone (ie, combination therapy increases vagal activity).
Chest, Apr 1, 2001
We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on... more We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on cardiac contractility, heart rate variability, and hemodynamics at rest and in response to a laboratory stressor. Subjects and instrumentation: Forty-one apneic patients were studied on three occasions: before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP treatment. The subjects were randomly assigned to receive effective treatment or placebo. Contractility and hemodynamics were determined with impedance cardiography, and parasympathetic activity was assessed by analysis of heart rate variability. Measures were determined at rest and in response to a stressor. Design and results: For the cardiac sympathetic (contractility) measures (preejection period, cardiac acceleration index [CAI], and low-frequency/high-frequency ratio) significant interactions were found in the combination treatment (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline, preparation, talking) [p < 0.01]. For these measures, there were no differences between the treatment groups or responses to the stressor on day 1. Levels in placebo-treated subjects did not change or respond on the subsequent study days. In the CPAP-treated subjects, there was a decrease in these indexes at baseline, which became significantly lower by day 11 (ie, CAI levels were 24 ⍀/s 2 , 22 ⍀/s 2 , and 14 ⍀/s 2 on day 1, day 3, and day 11, respectively). These measures also became responsive to the stressor by showing increased sympathetic activity (CAI levels on day 11 were 14 ⍀/s 2 at baseline, 32 ⍀/s 2 during speech preparation, and 36 ⍀/s 2 while speaking). The parasympathetic indexes, such as high-frequency power or band of heart rate variability as determined by spectral analysis, showed a significant day-by-treatment interaction (p < 0.005), whereas the CPAPtreated group had significantly more parasympathetic activity after 1 week of treatment. For the hemodynamic measures (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]), there were significant treatment-by-study day-by-test-period interactions (p < 0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP-treated patients. Conclusions: These results indicate that CPAP normalizes contractility, increases cardiac vagal tone, and changes hemodynamic regulation from being resistance dominated to being cardiac dominated. Thus, after 1 week of treatment with CPAP, many of the indicators of poor cardiac functioning in apnea patients are improved.
Annals of Behavioral Medicine, Feb 1, 2001
Objective: This exploratory study investigated the relation between psychological mood states and... more Objective: This exploratory study investigated the relation between psychological mood states and hemodynamic variables obtained at rest. Methods: We measured resting hemodynamic variables using impedance cardiography, blood pressure, heart rate, and the Profile of Mood States (POMS) in 71 participants. Results: Mood states were not significantly associated with heart rate, systolic, diastolic, or mean arterial pressure. In comparison with these basic measures of physiology, a number of impedance derived measures of hemodynamics were associated with mood states. Log stroke volume was negatively correlated with POMS tension-anxiety (r =-.319, p = .009) and fatigue-inertia (r =-.316, p = .009). Log cardiac output was negatively associated with fatigue-inertia (r =-.346, p < .01). Log total peripheral vascular resistance was positively correlated with POMS fatigue-inertia (r = .276, p = .024). Conclusions: Our findings suggest that mood states are associated with hemodynamic variables underlying blood pressure.
Sleep and Breathing, Nov 7, 2006
Sleep, Mar 1, 1997
Patients with obstructive sleep apnea (OSA) are often hypertensive, and both apneics and hyperten... more Patients with obstructive sleep apnea (OSA) are often hypertensive, and both apneics and hypertensives are reported to have increased sympathetic nerve activity. We measured plasma norepinephrine (NE) levels, clearance, and release rate among 65 subjects who breathed room air, a hypoxic gas mixture, and the hypoxic mixture combined with intermittent breath holding. Apneics' plasma NE across all three breathing conditions was 307 pg/ml compared with the non-apneics' level of 248 pg/ml (p = 0.017). NE clearance increased from 3.2 IIminute to 3.9 IIminute when subjects breathed a hypoxic gas mixture (p < 0.001). NE clearance was similar among normal controls, apneics, and hypertensives. The rate at which NE was released from sympathetic nerves into the bloodstream was higher among hypertensives but not among apneics while subjects breathed room air. Hypoxia increased the NE-release rate from 892 ng/minute to 1,042 ng/minute (p < 0.001) and increased the NE-release rate more among apneics than non-apneics (p < 0.001). The NE-re1ease rate response to hypoxia and hreath holding differed between hypertensives and normotensives (p < 0.001) and between apneics and non-apneics (p < 0.001). Normotensive apneics had the largest increase in NE release during hypoxia. Like other investigators, we found that plasma NE levels were increased among apneics. Calculation ofNE-release rate and correction for blood pressure status revealed a more complex situation. Apneics breathing room air had a normal NE-release rate; any increase in sympathetic neuronal NE release could be attributed to apneics who were also hypertensive. However, apneics had a greater NE response to hypoxia. These results suggest that apneics are susceptible to transient increases in sympathetic nervous activity and that hypertensive apneics maintain increased sympathetic nervous release of NE in the daytime.
Psychosomatic Medicine, 1999