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. Author manuscript; available in PMC: 2011 Jul 1.
Published in final edited form as: Hypertension. 2010 May 10;56(1):75–81. doi: 10.1161/HYPERTENSIONAHA.110.150011

Greater orthostatic tolerance in young black compared to white women

Kumba Hinds 1, Nina Stachenfeld 1
PMCID: PMC2909588  NIHMSID: NIHMS203492  PMID: 20458005

Abstract

We hypothesized that orthostatic tolerance is higher in young, healthy black compared to white women. To determine orthostatic tolerance, twenty-two women (11 black, 11 white) underwent graded lower body negative pressure to presyncope. We measured blood pressure, heart rate, and R-R interval (ECG) continuously at baseline and through all levels of lower body negative pressure. Blood samples were taken at baseline and presyncope for the measurement of plasma catecholamine concentrations, serum aldosterone concentration and plasma renin activity. Cumulative stress index (CSI), the sum of the product of time and lower body negative pressure, was the indicator of orthostatic tolerance. Orthostatic tolerance in the black women was greater than in the white women [CSI=-1003 (375) vs. -476 (197) P < 0.05]. While P[NE] increased in both groups at presyncope, the increase was greater in black [Δ P[NE] 167 (123)] versus white women [86 (64), P < 0.05], as were the increases in PRA [Δ PRA 2.6 (1.0) versus 0.6 (0.9) ng ANG II·ml-1 ·hr-1, P < 0.05, for black and white women, respectively). Although heart rate increased and R-R interval decreased to a greater extent during lower body negative pressure in black women compared to white women [ANOVA, P < 0.05)], baroreflex function (i.e. slope R-R interval vs. systolic blood pressure) was unaffected by race. These data indicate that orthostatic tolerance is greater in black compared to white women, which appears to be a function of greater sympathetic nervous system responses to orthostatic challenges.

Keywords: blood pressure, racial differences, arterial stiffness, sympathetic nervous system

Introduction

Orthostatic tolerance is a measure of the ability to maintain consciousness during changes in posture. Orthostatic stress induced by changes in posture, or by lower body negative pressure (LBNP), causes blood volume shifts to the lower extremities resulting in a fall in central blood volume. This fall in central blood volume stimulates both cardiopulmonary and arterial baroreceptors, leading to compensatory increases in heart rate and peripheral vasoconstriction. Despite the complex physiological systems evolved to maintain blood pressure during changes in posture, orthostatic intolerance is a relatively common blood pressure dysfunction in healthy young people, and is more common in women than in men 1,2.

Racial differences in blood pressure regulation have been well documented with regard to hypertension, and on the whole have indicated that hypertension is more prevalent in the black versus white population 3. Moreover, hypertension manifests at a younger age in black compared to white people and there are racial differences in the mechanisms that regulate blood pressure 4,5. With regard to orthostatic tolerance, in response to a 3.75 min standing test mean arterial pressure (MAP) increased in black subjects but fell in white and Asian subjects indicating differences in response to postural challenges across the three races 6. Finally, although black subjects display smaller increases in muscle sympathetic nerve activity (MSNA) during baroreceptor unloading compared to white subjects 4, forearm vasoconstriction is greater in black subjects, which would suggest enhanced sympathetic vascular transduction 4,5.

Even though orthostatic intolerance disproportionally affects women, studies that have addressed racial differences in cardiovascular responses to maximal lower body negative pressure have focused on men 4 or have not determined sex differences if women were included in the study 5. In light of the documented sex differences in orthostatic tolerance and racial differences in blood pressure regulation, we speculated that black and white women would respond differently to orthostatic stress induced by LBNP. We hypothesized that orthostatic tolerance would be greater in black compared to white women.

Methods

Subjects

Twelve black and twelve white women were recruited into the study. Subjects self identified race which in all cases was consistent with their visually observed phenotype. Given documented differences in blood pressure regulation, and disparities in related clinical outcomes between black and white people, we chose to focus solely on these two populations excluding other races. Twenty-four women completed the experimental protocol. Two individuals, one black and one white, were excluded from data analysis due to a failure to experience presyncopal symptoms at lower body negative pressure test termination so 11 subjects in each group were included in the analysis. One test was terminated due to technical difficulties and the second was ended prematurely because the subject did not comply with the experimental protocol: she ended the test in the absence of any symptoms, and told investigators that she had not felt any symptoms but ended the test prematurely because she felt nervous (white subject). Thus, twenty-two women were included in the analysis. All subjects were young, healthy, nonsmoking women with normal body mass index (BMI) who were not taking hormonal contraceptives or any other medication. All women provided written informed consent; this investigation was approved by the Human Investigation Committee at Yale University School of Medicine.

Experimental Protocol

All testing was conducted in an environmental chamber (Ta = 28°C). Upon arrival, hydration state was immediately assessed from urine specific gravity. Specific gravity was 1.001-1.02 in all subjects. Following the urine sample, the subject was weighed to the nearest 10 g on a beam balance, positioned in a lower body negative pressure chamber and instrumented for the measurement of beat-to-beat arterial pressure and heart rate (Finometer, Finapres Medical Systems, The Netherlands) on the middle finger of the right hand and R-R interval (ECG, Powerlab, AD Instruments, Colorado Springs, CO). Blood pressure measurements for all the results were derived from beat to beat blood pressure measurements from the Finometer. An automated blood pressure cuff (Colin Medical Instruments, Komaki, Japan) was also placed on the left arm for standard brachial artery measurements. A 21-gauge Teflon catheter was placed in an antecubital or forearm vein of the left arm and maintained with a heparin block (20 U/ml).

Assessment of Orthostatic Tolerance

We used graded LBNP to presyncope to determine orthostatic tolerance 7-9. The subjects lay supine, sealed at the iliac crest enclosed in the LBNP box. All measurements were preceded by a 30-min quiet rest period. At the end of this 30-minute rest period, a blood sample was taken for the measurement of catecholamines [(epinephrine (EPI), norepinephrine (NE)], plasma renin, activity (PRA) and serum aldosterone (S[ALD])]. Following the blood sample, we recorded HR, R-R interval (ECG) and beat-to-beat blood pressure for three minutes while the subjects rested quietly. Following this resting phase, maximal orthostatic tolerance was determined using similar methods to Fu et al 10,11 in which progressive LBNP is applied to presyncope. Lower body negative pressure began at -15 mm Hg for three minutes, then increased to -20 mm Hg followed by an increase of -10 mm Hg every three minutes until presyncope. Presyncope was defined as a decrease in SBP (finger blood pressure, Finometer) to <80 mm Hg, a decrease in SBP to <90 associated with symptoms of lightheadedness, nausea, sweating or diaphoresis, or progressive symptoms of presyncope accompanied by a request from the subject to terminate the test 12. In these studies, all women experienced presyncopal symptoms and most achieved an SBP < 90 mm Hg, with only one black and one white subject experiencing symptoms at SBP > 90 mm Hg. A blood sample was drawn immediately following presyncope for the measurement of catecholamines, S[ALD] and PRA.

Determination of orthostatic tolerance

We used a cumulative stress index (CSI) to determine orthostatic tolerance. The CSI was calculated as the sum of the product of time and level of LBNP 10,11 and the lower body negative pressure tolerance index (LTI) was calculated as the sum of the product of duration spent at each negative pressure and change in pressure from the previous stage 13. A more negative CSI, or greater LTI, indicated a higher negative pressure attained prior to presyncopal symptoms and thus higher orthostatic tolerance. We assessed baroreflex responses by examining the slope of the average R-R interval (from ECG) as a function of systolic blood pressure and of lower body negative pressure 14. The average R-R interval over the last two minutes of each stage and the corresponding stage of lower body negative pressure for each subject was used to determine the linear relationship between R-R and SBP/LBNP. We also determined R-R interval and LBNP over the last minute and the minute prior to the final minute to allow for comparisons among women who experienced syncope at different levels of LBNP. All data were recorded using a 16-channel PowerLab system with LabChart 6 software (AD Instruments).

Blood analysis

Blood samples were separated immediately into aliquots. The first was added to a plain tube with no additive for analysis of S[ALD], a second aliquot was placed in a pre-chilled K+ EDTA tube containing EGTA and glutathione for analysis of epinephrine (P[EPI]) and P[NE] and a final aliquot was also placed in a pre-chilled K+ EDTA tube for the analysis of plasma renin activity (PRA). All tubes were centrifuged, and the plasma or serum pipetted off for analysis.

Catecholamines were analyzed using high performance liquid chromatography (HPLC) with electrochemical detection (Colorchem Detector, ESA Corp, Acton Ma). Serum concentration of aldosterone and PRA were measured using competitive binding radioimmunoassay methods. Intra- and interassay coefficients of variation for the midrange standards were respectively as follows: S[ALD] (175 pg/ml) 3.05% and 2.26% (Siemens Healthcare Diagnostics, Deerfield, IL), and PRA (3.9-7.5 ng/ml/hr) 2.36% and 2.43% (DiaSorin, Stillwater, MN).

Data Analysis

The statistical analysis was performed using SAS statistical software version 9.1 (SAS Institute Inc., Cary, NC). Independent t-tests were used to assess between group differences in CSI, LTI, age, body mass index (BMI), baseline mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, R-R interval, LBNP tolerance indices and the slopes obtained from regression analysis for analysis of R-R interval and blood pressure relationships. Repeated measures ANOVA determined trends in MAP, SBP, DBP, HR and R-R interval response over time during LBNP. Because not all of the subjects completed all of the LBNP levels, repeated measures ANOVA was conducted only for stages completed by all subjects (0, -15, -20). Separate ANOVA were used to analyze variables at the final completed stage of LBNP for each subject, and the final two minutes of LBNP preceding presyncope. Survival analysis was used to predict the probability of presyncope at each stage of LBNP. This probability was obtained from the hazard ratio according to the following calculation: Hazard ratio (Hr) = odds = p/(1-p), where p = Hr/(1+Hr). We also used survival analysis to predict the odds of presyncope for black compared to white women at each stage of LBNP. Data are expressed as mean (SD) in all tables, however for clarity, standard errors are shown in graphs. Differences were considered statistically significant when P < 0.05.

Sample size calculation

Sample size calculations were based on our primary outcome variable of interest: CSI (orthostatic tolerance). The desired statistical test was two-sided and we assumed an alpha level of P = 0.01 for our sample size calculations to account for multiple comparisons 15. We used a difference in CSI of 272 (102) to calculate statistical power 11. A sample size of 8 women per group allowed us >80% statistical power (1-β >0.80) to detect a 35% difference in CSI between groups.

Results

Physical characteristics were similar between the racial groups (Table 1), as were resting cardiovascular variables (Table 2) and blood hormone concentrations (Table 3). The cumulative stress index was lower [-1003.5 (375.8) vs. -476 (197.5) P < 0.05, Fig. 1] and LTI was higher [(218 (44.8) vs. 150.8 (40.2), P < 0.05)] in black versus white women. For all blood pressure and heart rate variables, presyncopal decreases from baseline, recovery from presyncope, and recovery from baseline were similar for the racial groups (Table 2). From the last completed stage to the minute preceding the final minute of presyncope, HR increased to a greater extent in blac23.9k compared to white women (Table 2, P < 0.05). Similarly, during the final two minutes preceding presyncope, R-R interval declined to a greater extent in black compared to white women (Table 2, P < 0.05).

Table 1. Baseline subject characteristics.

Body mass index (BMI), R-R wave interval (R-R), mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Values are mean (standard deviation).

Subject characteristic Black White
BMI, kg/m2 23.8 (3.6) 22.4 (2.5)
Age, yr 20.9 (1.0) 21.3 (3.6)
Heart rate, beats/min 70 (5) 68 (10)
R-R interval, msec 846 (88) 892 (164)
MAP, mm Hg 75 (10) 75 (12)
SBP, mm Hg 111 (7) 116 (19)
DBP, mm Hg 59 (12) 57 (11)
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Table 2. Cardiovascular responses to lower body negative pressure.

Cardiovascular responses are shown at each level of lower body negative pressure (LBNP) common to all subjects, the final completed stage of LBNP (Final), and the final two minutes of LBNP (End -1 and End). Mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), R-R wave interval (R-R) and cardiac output (CO). Blood pressure and CO measurements are derived from beat to beat blood pressure measurements from the Finometer. *Significantly different between black and white women. Values are mean (standard deviation). Differences were considered statistically significant at P < 0.05.

LBNP 0 -15 -20 -30 -40 Final End – 1 End
MAP, mm Hg
 Black 75 (10) 78 (13) 77 (12) 76 (13) 75 (12) 72 (15) 72(18) 65(15)
 White 75 (12) 72 (15) 68 (19) 70 (14) 70 (15) 68 (11) 68 (15) 66 (18)
SBP, mm Hg
 Black 111 (6) 115 (8) 113 (10) 110 (13) 106 (13) 91(13) 98 (19) 90 (24)
 White 116 (18) 113 (18) 104 (22) 106(19) 104 (20) 100 (17) 107 (22) 100 (15)
DBP, mm Hg
 Black 59 (12) 62 (13) 61 (12) 56 (10) 60 (12) 57 (15) 54 (12) 52 (15)
 White 57 (11) 54 (13) 52 (17) 58 (12) 61 (9) 57 (15) 62 (14) 58 (16)
HR, bpm
 Black 70 (5) 69 (4) 69 (5) 68 (24) 74 (5) 107 (6)* 96 (9)* 96 (8)*
 White 69 (10) 69 (12) 69 (11) 69 (10) 75 (12) 79 (15) 82 (15) 82 (18)
RR, msec
 Black 846 (88) 859 (94) 877 (92) 779 (93) 769 (69) 554 (90) 598 (127)* 576 (128)*
 White 892 (164) 913 (169) 907 (166) 850 (171) 772 (163) 778 (154) 782 (190) 794 (200)
CO, L/min
 Black 4.8 (1.8) 4.6 (2.4) 4.8 (2.3) 4.7 (2.2) 4.6 (1.4) 4.0 (1.4) 4.4 (2.6) 4.1 (2.2)
 White 4.9 (1.9) 4.8 (1.8) 4.8 (1.9) 4.9 (1.6) 4.7 (2.1) 4.2 (1.4) 4.1 (1.2) 4.1 (2.3)
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Table 3. Blood hormone responses to lower body negative pressure.

Blood hormone concentration at baseline, presyncope and the change from baseline to presyncope. Plasma concentrations of norepinephrine (P[NE]), epinephrine (P[EPI]), serum aldosterone (S[ALD]), and plasma renin activity (PRA, ng ANG II/ml/hr). *Significantly different between black and white women. †Denotes that one subject was removed from the analysis due to an insufficient blood sample. Values are mean (standard deviation). Differences were considered statistically significant at P < 0.05.

Hormone Black White†
Baseline Presyncope Change Baseline Presyncope Change
P[NE], pg/mL 197 (144) 365 (174)* 167(123)* 146 (96) 232 (101) 86 (64)
P[EPI], pg/mL 20 (18) 64 (62) 49 (63)* 23 (19) 30 (8) 7 (20)
S[ALD] pg/ml 98.9 (43.5) 107.7 (45.6) 8.8 (16.4) 109.9 (41.1) 119.8 (63.1) 5.7 (10.6)
PRA, ng/ml/hr 0.9 (0.5) 2.8 (1.5) 1.9 (1.5)* 2.4 (2.0) 3.3 2.3 0.4 (0.3)
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Figure 1.

Figure 1

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Individual subjects' and mean cumulative stress index (CSI) for black women and white women. The dark circles for each race represent mean CSI ± standard error. The CSI is the sum of the product of each level of lower body negative pressure (LBNP) and the time spent at each level of LBNP. CSI is expressed as mm Hg × min. A more negative CSI indicated a higher negative pressure attained prior to presyncopal symptoms and thus higher orthostatic tolerance.

Survival analysis demonstrated that time to presyncope was greater in black compared to white women [median time to presyncope = 23.9 (1.3) min vs. 17.2 (1.4) min, Fig. 2, for black and white women, respectively, P < 0.05]. Seventy-five percent of black women survived through 26.2 minutes of the LBNP test compared to 21.0 minutes for 75% of white women. Furthermore, at a given stage of LBNP there was an 86% probability of a black woman experiencing presyncope at a later stage than a white woman [Hazard ratio= 0.157].

Figure 2.

Figure 2

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Survival probability as a function of lower body negative pressure (mm Hg) for black women (solid line) and white women (dotted line).

Baroreflex Responses or R-R interval-SBP relationship

The relationship between R-R interval, SBP and LBNP was examined through -40 mm Hg negative pressure to measure baroreflex responses. We had to remove one (white) subject who was presyncopal prior to -40 mm Hg from the analysis to facilitate meaningful comparisons between the two groups. Race did not impact baroreflex response during increasing lower body negative pressure [slopes, -14.6 (6.4) and -16.8 (8.3) R-R interval msec/SBP mm Hg, for black and white subjects, respectively Fig. 3A and B). We also examined the relationship between R-R interval and LBNP including the stages 0, -15, -20, the final completed stage, and the final two minutes immediately preceding presyncope and test termination. Race did not impact baroreflex responses during increasing lower body negative pressure [slopes, -5.7 (2.0) and -3.5 (4.0), R-R interval msec/LBNP mm Hg, for black and white subjects, respectively].

Figure 3.

Figure 3

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A. Baroreflex data from representative black and white subjects during lower body negative pressure. Dotted line represents linear regression for the white subject (r2=0.89, range, 0.72 – 0.89) and solid line represents linear regression for the black subject (r2=0.85, range, 0.69 – 0.85). B. Baroreflex slope in black and white subjects. Mean ± SEM.

Hormonal Responses

Plasma NE concentration increased from baseline in both racial groups, but P[NE] was greater in black versus white women at presyncope (Table 3, P < 0.05) and there was a trend for a greater increase in P[NE] from baseline to presyncope in the black women (P< 0.05). There were no racial effects on P[EPI], S[ALD], or PRA at presyncope, but the change in PRA from baseline to presyncope was greater in black versus white women because PRA was slightly lower in the black women at baseline (Table 3, P < 0.05).

Discussion

This is the first study to investigate racial differences in orthostatic tolerance in young healthy women. Our primary finding is that black women had greater orthostatic tolerance than white women of similar age, BMI and health status. Resting cardiovascular and hormonal variables were similar between the two groups and key physical characteristics and cardiovascular variables known to impact blood pressure regulation were also similar between the two groups. Lower body negative pressure induced greater increases in P[NE] from baseline to presyncope in black subjects compared to white subjects, and P[NE] was greater at presyncope in black compared to white subjects. Moreover, PRA increased in response to LBNP only in black subjects, suggesting some increase in renal sympathetic activity and that the renin-angiotensin-system may play a role in the higher orthostatic tolerance in these young black women. Most importantly, these data suggest that mechanisms involved in hypertension in middle age and older black men and women may already be present in young healthy women.

Lower body negative pressure induces a downward shift of blood volume, with pooling of blood in the lower limbs, rendering this volume no longer available for central hemodynamics. Cardiopulmonary and arterial baroreceptors, located in the in pulmonary vessels, the carotid sinus and aortic arch, sense changes in central pressure induced by the volume shift and send signals to the nucleus tractus solitarius of the brain to protect blood pressure and maintain consciousness. The sympathetic nervous system plays a crucial role in this baroreceptor-mediated blood pressure regulation by activating systems that increase vasoconstriction in the periphery to maintain blood pressure as long as possible. During a fall in central pressure, sympathetic nervous system activation also leads to renin and angiotensin II release, which would also contribute to increases in peripheral resistance. Thus, peripheral vascular resistance plays a critical role in maintaining blood pressure during orthostatic challenges such as LBNP.

Our findings are consistent with earlier data indicating lower compliance, or greater stiffness (as measured by pulse wave velocity), in the peripheral vascular system in black subjects 16-19. A recent study in black and white adolescent subjects demonstrated that race is a strong predictor of arterial stiffness 16 and there a number of studies indicating lower compliance in the cardiovascular system of black versus white adult subjects 17-19. This is of particular interest because early changes in endothelial function, arterial stiffness and intima wall thickness in young, normotensive individuals is associated with greater risk of hypertension in later years 17-19. In the present investigation, we did not see racial differences in the baroreflex response as measured by the relationship between R-R interval and SBP, supporting the contention that the mechanism for the racial differences in orthostatic tolerance might lie in the periphery. The extent to which lower body negative pressure translocates blood volume depends on the compliance of the vascular system. Thus greater venous compliance could potentially increase the extent of blood pooling during LBNP leading to greater orthostatic stress. A system with greater compliance and lesser venous tone, results in a slower response because greater volume shifts are required to induce a change in central venous pressure. For example, orthostatic tolerance is reduced in well-trained athletes who have a more compliant vascular system 12.

We recognize that P[NE] is not a direct measure of sympathetic nervous system activity; however, because NE is released from sympathetic nerve endings during sympathetic nervous system activation, changes in NE are an indirect indicator of the magnitude of a sympathetic response and are correlated with more direct measures such as MSNA 20. Moreover, enhanced NE responses during LBNP are usually associated with greater orthostatic tolerance 21. The primary limitation in interpreting plasma catecholamine concentrations is that a single measurement does not distinguish between changes in NE release or uptake. Using microneurography, Ray et al. 5 demonstrated that young black men and women exhibit lower muscle sympathetic nerve activity in response to baroreceptor unloading, but greater peripheral vasoconstriction for a given increase in MSNA relative to their white counterparts 5. These findings are consistent with an earlier study demonstrating white and black men to have similar orthostatic tolerance and similar increases in forearm vascular conductance despite relatively smaller changes in sympathetic activity in the black subjects 4. Taken together, these studies indicate greater vascular reactivity to sympathetic stimulation in black versus white men. The application of these MSNA studies in men to the women in our study may be limited because although MSNA is an excellent predictor of peripheral vascular resistance in men, this is not the case in women 22. This observation has been interpreted to indicate that sympathetic nerve activity plays greater role in total peripheral resistance in young men than it does in young women 22.

Race and sex differences in vascular reactivity to β2-adrenergic activation may also have influenced our findings. White women are more sensitive to β2-adrenergic receptor stimulation compared to white men, as demonstrated by greater forearm vasodilation in response to albuterol infusions 23. Within both sexes, black subjects have attenuated nitric oxide dependent vasodilation relative to their white counterparts 24,25, likely the result of decreased nitric oxide production and endothelial dysfunction 25,26. Moreover, black subjects have reduced β2-adrenergic sensitivity as demonstrated by a blunted pulse wave velocity response to isoproterenol when compared with white subjects matched for age, sex and BMI 27. Thus differential interactions between sympathetic activity, endothelial function, and β2-receptors may contribute to the different responses between the black and white women to the orthostatic challenge in the present investigation.

Plasma renin activity increased to a greater extent in black compared to white women during LBNP and may reflect increased sympathetic nervous system activity at the kidney. Our findings are consistent with earlier studies demonstrating that low PRA is associated with reduced orthostatic tolerance 28. Thus the PRA response in the black women likely indicates RAAS stimulation resulting in greater peripheral vasoconstriction in response to the loss of central blood volume induced by the LBNP challenge 28. The RAAS has been identified as an important mechanism for hypertension in both black men and women 29. The greater PRA responses in black women during LBNP appear to support an important role for this system in blood pressure regulation and perhaps are an early reflection of blood pressure dysregulation.

In summary, our data demonstrated significantly greater orthostatic tolerance in young, healthy black women compared to their white counterparts. This difference in orthostatic tolerance was not associated with any racial difference in baroreflex function, but was associated with greater increases in P[NE], suggesting a greater sympathetic nervous system response to lower body negative pressure in the black subjects. The high orthostatic tolerance in the black women may also reflect vascular stiffness, or lower compliance, and perhaps contribute to hypertension later in life 16-18.

Limitations

Lower body negative pressure has been used in this study as a model orthostatic of stress because many of the physiological changes are similar to standing and to head up tilt (HUT). Most importantly, both HUT and LBNP result in central hypovolemia and similar baroreceptor unloading 30. However, LBNP is not a perfect model for orthostatic stress because some of the redistribution of blood volume during LBNP does not specifically mimic that of standing. For example, splanchnic volume decreases during application of LBNP, but increases during HUT, the latter being an action more similar to standing 31.

Another limitation of this investigation is that we did not measure resting cardiovagal or sympathetic baroreceptor responses to acute changes in blood pressure. Future research into the mechanisms contributing to greater orthostatic tolerance in young black and white women should include measures of endothelial function and cardiovascular stiffness. Thus, further study of racial differences in orthostatic tolerance is necessary to elucidate the mechanisms behind, and the potential clinical consequences of, racial differences in orthostatic tolerance. Another limitation in our study is that we did not control for menstrual cycle phase. Although controlling for phase of the menstrual cycle is ideal, orthostatic tolerance does not change across the cycle 32,33. Moreover, the magnitude of the difference between the black and white subjects suggests there would be minimal impact of reproductive hormones on these racial differences. However, although phase of the menstrual cycle can influence baroreceptor sensitivity and sympathetic outflow, these changes do not lead to alterations in vascular resistance34. Finally, although the differences in orthostatic tolerance between the racial groups were striking, our sample size was low so these data may be interpreted with caution.

Perspectives

The racial differences in orthostatic tolerance we observed in this study were substantial and physiologically meaningful. We defined women as high (CSI>755) or low (CSI<425) tolerance, which is consistent with published literature 10,11; there were three white women with high orthostatic tolerance, but there was only one black woman who would be defined as having low tolerance. While enhanced orthostatic tolerance may be advantageous in these young women, this advantage may be a harbinger of the well-documented cardiovascular disease more prevalent in black women later in life 35. Moreover, women are typically described as having lower orthostatic tolerance than men, but these observations have been made primarily in white women or in mixed groups. Our data suggests that this generally accepted sex difference might not be appropriate for black women. Our studies should be followed up with more direct measures of sympathetic nervous system activity (i.e. MSNA) as well as measures of arterial stiffness such as pulse wave velocity.

Acknowledgments

We gratefully acknowledge the technical support of Andrew Grabarek, BS, and Cheryl Leone MS. We would also like to thank Megan Wenner PhD for her assistance with the writing of this manuscript and the cooperation of the volunteer subjects.

Sources of funding. This study was supported by an NIH Research Supplement to Promote Diversity in Health-Related Research, and by general funds from NIH HL071159.

Footnotes

Disclosures: none.

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