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. Author manuscript; available in PMC: 2021 Jul 1.
Published in final edited form as: Exp Physiol. 2020 May 27;105(7):1102–1110. doi: 10.1113/EP088535

Augmented Resting Beat-to-Beat Blood Pressure Variability in Young Healthy Non-Hispanic Black Men

Benjamin E Young 1, Jasdeep Kaur 1, Jennifer R Vranish 2, Brandi Y Stephens 1, Thales C Barbosa 1, Jane N Cloud 1, Jing Wang 3, David M Keller 1, Paul J Fadel 1
PMCID: PMC7895300  NIHMSID: NIHMS1599411  PMID: 32362031

Abstract

The prevalence of hypertension in Black (BL) individuals exceeds other racial groups. Recently, resting beat-to-beat blood pressure (BP) variability has been shown to better predict cardiovascular risk and detect target organ damage compared to ambulatory BP monitoring. Given the heightened risk in BL, we hypothesized young BL men would exhibit augmented beat-to-beat BP variability compared to white (WH) men. Furthermore, given studies reporting reduced vasodilation and augmented vasoconstriction in BL, we hypothesized BL men would exhibit augmented total peripheral resistance (TPR) variability. In 45 normotensive men (24 BL), beat-to-beat BP (Finometer) was measured during 10–20 minutes of quiet rest. Cardiac output (CO) and TPR were estimated (Modelflow). Despite similar resting BP, BL men exhibited greater BP standard deviation (e.g., systolic BP SD; BL: 7.1 ± 2.2; WH: 5.4 ± 1.5 mmHg, P=0.006), compared to WH men, which was accompanied by a greater TPR SD (P=0.003), but not CO SD (P=0.390). Other traditional variability measures provided similar results. Histogram analysis indicated BL men exhibited a greater percentage of cardiac cycles with BPs higher (>+10 mmHg) and lower (<−8 mmHg) than mean systolic BP compared to WH (interaction, P<0.001), which were accompanied by a greater percentage of cardiac cycles with high/low TPR (P<0.001). In a subset of subjects (n=30), reduced sympathetic baroreflex sensitivity (BRS) was associated with augmented BP variability (R=−0.638, P<0.001), whereas cardiac BRS had no relationship (P=0.447). Herein, we document an augmented beat-to-beat BP variability in young BL men, which coincided with fluctuations in vascular resistance and reduced sympathetic BRS.

Keywords: Total Peripheral Resistance, Cardiac Output, Racial Differences, African American, Caucasian American, Arterial Baroreflex

Introduction

The prevalence and severity of hypertension (HTN) in Non-Hispanic Black (BL) individuals are far greater than in any other racial group, with more than 40% of all BL adults in the United States diagnosed with HTN (Benjamin et al., 2019; Burt et al., 1995). This increased prevalence of HTN augments the risk for cardiovascular events. Indeed, BL individuals are at nearly twice the risk of cardiovascular disease-related morbidity and mortality compared to their Non-Hispanic White (WH) counterparts (Mozaffarian et al., 2015). While the disparate incidence of HTN in BL individuals is well-documented (Carnethon et al., 2017), the underlying contributing factors remain incompletely understood.

Recent studies indicate that augmented resting beat-to-beat BP variability provides prognostic information regarding cardiovascular outcomes and target organ damage beyond traditional 24-hour ambulatory or home-based BP monitoring (Dawson, Manktelow, Robinson, Panerai, & Potter, 2000; Webb, Mazzucco, Li, & Rothwell, 2018; Wei et al., 2014). Given the heightened cardiovascular risk in BL individuals and higher prevalence of conditions associated with target organ damage, such as chronic kidney disease (Carnethon et al., 2017), it is plausible that BL individuals exhibit an augmented beat-to-beat BP variability at rest. However, to our knowledge, this has never been examined in BL individuals. This is important because, while BL individuals have been shown to exhibit augmented 24-hour BP variability (Muntner et al., 2015), higher frequency oscillations in BP (i.e., beat-to-beat BP variability) may impose a greater challenge to the cardiovascular system (Sagawa, 1983; Wei et al., 2014).

The importance of the arterial baroreflex for the regulation of beat-beat BP has been well documented (Fadel, 2008; Fadel, Ogoh, Keller, & Raven, 2003; Lanfranchi & Somers, 2002). Furthermore, the baroreflex control of sympathetic nerve activity and associated changes in the peripheral vasculature have been shown to be the primary means by which the arterial baroreflex regulates BP (Keller et al., 2003; Ogoh, Fadel, Monteiro, Wasmund, & Raven, 2002; Ogoh et al., 2003). However, few studies have examined sympathetic baroreflex sensitivity in BL individuals.

Herein, resting beat-to-beat BP variability was measured using traditional measures of variability and novel histogram distribution analysis, and compared between young BL and WH men. We tested the hypothesis that BL men would present with an augmented resting beat-to-beat BP variability compared to their WH counterparts. In addition, considering the growing body of literature reporting that alterations in peripheral vascular function (i.e., reduced vasodilation and augmented vasoconstriction) may occur early in life in BL individuals, prior to any overt disease (Brothers, Fadel, & Keller, 2019; Stein, Lang, Nelson, Brown, & Wood, 1997; Stein, Lang, Singh, He, & Wood, 2000), we further hypothesized that BL men would present with an augmented resting beat-to-beat total peripheral resistance (TPR) variability compared to their WH counterparts. Lastly, in a subset of individuals, we also characterized spontaneous sympathetic and cardiac baroreflex sensitivity (BRS).

METHODS

Ethical Approval

All subjects provided written informed consent after explanation of the study procedures and experimental measures, which were approved by the Institutional Review Boards at the University of Missouri (project number 120042) and the University of Texas at Arlington (project number 2016–0783). All aspects of the study conformed to the standards set by the Declaration of Helsinki, except for registration in a database.

Subjects

For the present investigation, 45 young, healthy men (24 BL, 21 WH) were recruited. Racial identification was determined via self-report during screening. All subjects further identified both biological parents as either African American or White. No mixed racial background subjects were included. All subjects were free from any overt disease, did not smoke or use tobacco, and did not take any medications. Subjects reported being recreationally active and none were training competitively. The resting cardiovascular data used for this study are a combination of retrospective analysis from previously published data (WH, n=15; BL, n=15 (Vranish et al., 2018)) as well as prospective data analysis (WH, n=6; BL, n=9). However, the data analyses and hypotheses tested in the present investigation are original and independent from those in the previous study.

Experimental Measurements

Heart rate (HR) was measured using a lead II surface electrocardiogram (Quinton; Bothell WA). Beat-to-beat arterial BP was measured via finger photoplethysmography (Finapres Medical Systems; Amsterdam, the Netherlands), and verified by automated sphygmomanometer BP (Welch Allyn; Skanateales Falls, NY) measurements. Respiratory movements were monitored using a strain-gauge pneumobelt secured around the abdomen (Pneumotrace, UFI, Morro Bay, CA) to ensure consistent respiration throughout the protocol. In a subset of individuals (n=15 BL, N=15 WH), microneurography was performed to measure post-ganglionic muscle sympathetic nerve activity (MSNA) as previously described (Holwerda, Restaino, et al., 2016; Vranish et al., 2018; Young, Holwerda, Vranish, Keller, & Fadel, 2019). Briefly, a unipolar tungsten microelectrode was inserted percutaneously just below the fibular head. The electrode was then positioned into muscle fascicles within the peroneal nerve. The signal was amplified, band-pass filtered (700–2000 Hz), rectified, and integrated (0.1 s time constant) to provide a mean voltage neurogram (Nerve Traffic Analyzer Bioengineering, University of Iowa). MSNA was identified by pulse synchronous bursts and confirmed with muscle afferent stimulation, in the absence of skin afferent stimulation.

Experimental Protocol

Prior to the study visit, subjects were instructed to arrive to the laboratory at least 3 hours post-prandial, and having refrained from exercise and alcohol for 24 hours, and caffeine for 12 hours. Upon arrival to the laboratory, subjects were instrumented for neural cardiovascular measures. After instrumentation, subjects rested supine for 10–20 minutes in a dimly lit, temperature-controlled room (21–23°C), while HR, BP, respiration, and MSNA (n=30) were continuously recorded. Throughout this resting period, subjects were instructed to remain quiet and awake. All neural cardiovascular measures were simultaneously collected at 1,000Hz in commercial acquisition software (PowerLab; AD Instruments) and stored offline for later analysis.

Data Analysis

Resting cardiovascular and neural measures were calculated as mean values over the duration of the entire 10–20 minute resting period. Mean arterial pressure (MAP) was calculated as an average of the automated sphygmomanometer BPs obtained during the resting period, and Finometer BP waveforms were calibrated one-time to the average of these systolic BP (SBP), diastolic BP (DBP), and MAP measurements. A minimum of 5 sphygmomanometer BPs was used to define resting BP values in all but one subject, in whom only 3 measurements were used due to technical issues with the automated BP monitor. This ensured that BP measurements derived from the Finometer matched absolute value BP obtained from the automated sphygmomanometer. Stroke volume (SV) was estimated using the Modelflow method (Jansen et al., 2001) and cardiac output (CO) calculated as SV multiplied by HR. TPR was calculated as MAP divided by CO.

Customized LabView (National Instruments, Austin, Texas) software was used to analyze MSNA, as previously described (Fairfax et al., 2013; Holwerda, Restaino, et al., 2016; Vranish et al., 2018). Bursts of sympathetic outflow were identified by pulse synchronicity, signal to noise ratio of 3:1, and morphology of the burst. Neurograms were analyzed for resting MSNA, quantified as burst frequency (bursts/minute) and burst incidence (bursts/100 heartbeats).

BP, TPR, and CO Variability.

Commercial statistical software (SPSS statistics 24; IBM) was used to derive the following parameters: Mean, standard deviation (SD), range, and inter-quartile range (IQR; difference between 25th and 75th percentiles within-subject). These parameters were evaluated for SBP, DBP, MAP, CO, and TPR.

In addition, coefficient of variation [(SD/mean)*100] was calculated to describe the deviation of the sample relative to their mean values. Moreover, average real variability (ARV) was calculated using the following formula:

ARV=1N-1∑k=1N-1XK+1-Xk

where N denotes the absolute number of BP measurements, K denotes the chronological order of those measurements, and X represents the parameter of interest (i.e., MAP, SBP, DBP, CO, TPR), as previously described (Mena et al., 2005). However, none of these aforementioned statistical procedures provide insight into the distribution of the beat-to-beat variability. To quantify the distribution of BP/CO/TPR across the range of resting values, histograms were constructed using commercial software (SAS Studio, SAS Institute Inc.). First, beat-to-beat BP values were binned into 1 mmHg bins. Then, the percentage of cardiac cycles at each given measurement “distance” from the mean (i.e., 1 mmHg for BP) was calculated for each subject. Within each group, the percentage of cardiac cycles for each measurement bin were averaged to provide group mean data. These histograms therefore represent the relative percentage of cardiac cycles that each group exhibited at a given absolute value (delta) measurement from the mean. Thus, in the case of BP (SBP, DBP, and MAP), each bin represents the average percentage of cardiac cycles that each group exhibits a BP greater or less than the mean BP in 1 mmHg increments. The same binning procedure used for all BPs, was used for CO on a 100mL bin scale, and for TPR on a 0.2 mmHg/L/min scale.

Spontaneous Baroreflex Sensitivity

Sympathetic baroreflex sensitivity (sympathetic BRS).

Sympathetic baroreflex sensitivity (i.e., gain) was quantified across the entire resting period as described in detail previously (Holwerda, Vianna, et al., 2016). This assessment provides an operating point gain of the arterial baroreflex control of MSNA (Hart et al., 2010; Keller et al., 2004; Raven, Potts, & Shi, 1997). Briefly, DBP values are binned into 3-mmHg bins, and MSNA burst incidence were averaged over those 3-mmHg DBP bins. Weighted linear regression analysis of MSNA burst incidence and DBP was performed, with weighting based upon the number of cardiac cycles in each bin. Slopes of the resultant linear regressions were used as an index of sympathetic BRS. DBP was used for this analysis because changes in MSNA correlate most closely with changes in DBP (Sundlof & Wallin, 1978). Baroreflex slopes with an r-value greater than 0.5 were accepted.

Cardiac Baroreflex Sensitivity (cardiac BRS).

Beat-to-beat time series of SBP and R-R interval were analyzed using the sequence technique for estimating spontaneous cardiac BRS (Nevrokard, Izola, Slovenia), as previously performed in our laboratory (Holwerda et al., 2015). Briefly, sequences of 3 or more consecutive beats where SBP and R-R interval change in the same direction were identified as arterial baroreflex sequences. Sequences were only detected if the variation in R-R interval was greater than 5 ms, SBP changes were greater than 1mmHg, and longer than 3 cardiac cycles. A linear regression was applied to each individual sequence and only sequences with an R2 >0.85 were accepted. The slope of the SBP and R-R interval relationship was then calculated and averaged to provide a measure of spontaneous cardiac BRS. Spontaneous cardiac BRS was determined for all sequences combined, and also separately, for up sequences (SBP increases: R-R interval increases) and down sequences (SBP decreases: R-R interval decreases). Examination of up sequence and down sequence gains yielded similar results to those of the overall sequence gain analysis. Likewise, cardiac BRS analysis utilizing HR changes instead of R-R interval provided similar results. Therefore, only the overall gain for the SBP and R-R interval relationship is presented.

Statistical Analysis

Normality was assessed using the Shapiro-Wilk test, and when appropriate, nonparametric testing was performed. In the present investigation, non-normally distributed data did not influence the interpretation of any outcome measure. All between-group comparisons of the traditional statistical parameters (e.g., SD or ARV), subject characteristics, and spontaneous BRS measures were made using Student’s t-tests or Mann-Whitney U test using the commercial statistical software Sigmaplot 13 (Systate Software). Pearson product-moment correlation coefficients were performed between sympathetic BRS or cardiac BRS parameters and indexes of BP variability, to determine if there was an association between baroreflex sensitivity and BP variability. Between-group comparisons of histogram distributions (i.e., bins) were made using a generalized linear mixed effects model (GLIMMIX), with post-hoc comparisons made using Tukey’s Honest Significant Difference test, completed in SAS Studio. Importantly, due to the nature of the histogram construction, wherein, the percentage of cardiac cycles in all bins when summed must equal 100%, a main effect for group was omitted from the GLIMMIX procedure. The omission of a main effect for group did not impact the interaction term. All data are reported as mean ± SD, and significance was set a-priori at P<0.05.

Given the centralized nature of the histogram distribution(s), and the relatively low occurrence of fringe BP, CO, and TPR values, statistical analysis was performed on a sliding scale, to ensure sufficient observations in each bin for statistical comparison. Binning for the GLIMMIX procedure was applied to ensure a minimum of ~4% occurrences in each bin. Due to the lower percent occurrence of extreme BP, CO, or TPR values (>± 10mmHg, 1000 mL/min, 1 mmHg/L/min), data in these areas were summed for statistical analysis. This binning procedure resulted in 17 bins for all conditions (MAP, SBP, DBP, TPR, CO). For BP values, the following binned delta absolute value measurements away from the mean were used (<−10, −10 to −8, −7 and −6, −5, −4, −3, −2, −1, 0, 1, 2, 3, 4, 5, 6 and 7, 8 to 10, >10 mmHg). For presentation purposes the TPR histogram was truncated at +10mmHg/L/min, however, the BL men exhibited a few (<1%) cardiac cycles in this range, which were included in the statistical analysis for that bin.

RESULTS

Subject Characteristics

Subjects were of similar height (BL: 177 ± 7 cm; WH: 180 ± 6 cm, p=0.11), weight (BL: 77 ± 10 kg; WH: 79 ± 13 kg, p=0.55), and body-mass index (BL: 25 ± 3 kg/m2; WH: 25 ± 4 kg/m2, p=0.81); however, the BL group tended to be slightly younger (BL: 20 ± 2 years; WH: 22 ± 4 years, p=0.06). Resting SBP, DBP, MAP (see Table 1) and HR (BL: 59 ± 9 bpm; WH: 60 ± 8 bpm, p=0.94), and resting MSNA burst frequency (BL: 11 ± 6 bursts/min; WH: 12 ± 4 bursts/min, p=0.52) as well as MSNA Burst Incidence (BL: 18 ± 10 bursts/100hb; WH: 21 ± 6 bursts/100hb, p=0.40) were not significantly different between groups.

Table 1.

Measures of Blood Pressure (BP) Variability

Parameter Systolic BP (mmHg) Diastolic BP (mmHg) Mean BP (mmHg)
WH BL P-Value WH BL P-Value WH BL P-Value
Mean 121 ± 9 124 ± 7 0.154 67 ± 7 68 ± 8 0.611 85 ± 6 86 ± 6 0.276
Standard Deviation 5.4 ± 1.5 7.1 ± 2.2 0.006 3.6 ± 0.9 4.7 ± 1.2 0.001 4.2 ± 1.1 5.3 ± 1.3 0.004
Range 31.9 ± 9.2 40.6 ± 12.4 0.012 23.4 ± 5.8 30.6 ± 6.4 <0.001 26.2 ± 6.7 32.5 ± 7.2 0.004
IQR 7.5 ± 2.1 10.0 ± 3.6 0.007 5.0 ± 1.3 6.2 ± 1.7 0.014 5.6 ± 1.5 7.1 ± 2.0 0.005
Coefficient of Variation (%) 4.5 ± 1.3 5.7 ± 1.7 0.008 5.6 ± 1.5 7.0 ± 1.7 0.003 5.0 ± 1.3 6.1 ± 1.4 0.007
Average Real Variability 2.0 ± 0.4 2.4 ± 0.7 0.044 1.3 ± 0.3 2.1 ± 0.8 <0.001 1.3 ± 0.3 1.5 ± 0.4 0.012
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Values are mean ± SD. WH, Non-Hispanic White men (n=21); BL, Non-Hispanic Black men (n=24); IQR, Interquartile Range.

Beat-to-Beat BP variability

Beat-to-Beat SBP SD, range, IQR, coefficient of variation, and ARV were all significantly greater in BL men compared to WH men (Table 1). Likewise, BL men exhibited greater MAP and DBP SD, range, IQR, coefficient of variation and ARV.

Figure 1 depicts the SBP (Fig. 1A), and MAP (Fig. 1B) histogram distributions in BL compared to WH men. For SBP WH men exhibited a greater percentage of cardiac cycles within bins of ±2 mmHg around the mean SBP relative to BL men. In contrast, BL men exhibited a greater percentage of cardiac cycles in the bins on the higher end of their SBP distribution (bin >+10mmHg) compared to WH men. Notably, relative to WH men, BL men exhibited greater than double the percentage of cardiac cycles on this higher end of their SBP distribution (BL: 7.8 ± 5.8 % versus WH: 3.3 ± 3.2 %). Interestingly, BL men also exhibited a greater percentage of their cardiac cycles on the lower end of their SBP distribution (bins <−8 mmHg). Thus, while WH men exhibited more cardiac cycles with SBP values closer to their mean, BL men exhibited a greater number of cardiac cycles with SBP values further from the mean, on both the high and low ends of their distribution. Similarly, for the MAP histogram, WH men exhibited a significantly greater percentage of cardiac cycles within the bins around the mean MAP, while BL men exhibited a greater percentage of cardiac cycles on the high as well as low ends of the distribution (Fig. 1B). DBP histogram distributions revealed similar results to those of SBP and MAP (data not shown).

Figure 1.

Figure 1.

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Histogram analysis of systolic blood pressure (SBP; Fig. 1A) and mean arterial blood pressure (MAP; Fig. 1B) in Non-Hispanic Black (BL; n=24, red bars) and Non-Hispanic White (WH; n=21, blue bars) men. Areas of the histogram wherein both WH and BL men exhibit cardiac cycles (i.e., overlap) are denoted in purple. Data represent blood pressure values binned in 1 mmHg increments away from each respective mean value. For statistical analysis and because of the markedly different range in values between WH and BL men, a sliding bin scale was used to normalize all histograms to 17 bins (see Methods). Dotted lines represent the bounds of each statistical bin. Brackets denote areas of the histogram where there is a significant difference (P<0.05) for all bins within that bracket between BL men and WH men.

Beat-to-beat CO and TPR variability

CO mean, SD, range, and IQR were not significantly different between BL and WH men. However, CO coefficient of variation and ARV were significantly greater in BL men compared to WH men (Table 2). In contrast, TPR mean, SD, range, IQR, coefficient of variation, and ARV were all significantly greater in BL relative to WH men. Figure 2 depicts CO (Fig. 2A) and TPR (Fig. 2B) histogram distributions between BL and WH men. Histograms revealed no significant differences in CO distributions between BL men and WH men. However, similar to BP, TPR histogram distributions (Fig. 2B) indicated that WH men exhibited a significantly greater percentage of cardiac cycles around the mean TPR, while BL men exhibited a significantly greater percentage of cardiac cycles further away from the mean on both ends of the TPR histogram. For example, in the bin with TPR values >+2 mmHg/L/min, BL men exhibited 7.8 ± 5.9 % of their cardiac cycles compared to WH men, who only exhibited 2.5 ± 2.3 % of their cardiac cycles (see Fig. 2B).

Table 2.

Measures of Cardiac Output (CO) and Total Peripheral Resistance (TPR) Variability

Parameter CO (mL/min) TPR (mmHg/L/min)
WH BL P-Value WH BL P-Value
Mean 6694 ± 944 6275 ± 1394 0.252 12.9 ± 1.3 14.4 ± 3.0 0.030
Standard Deviation 548 ± 202 597 ± 179 0.390 1.0 ± 0.3 1.5 ± 0.6 0.003
Range 3666 ± 1038 3993 ± 952 0.275 6.9 ± 1.9 10.8 ± 5.0 0.002
IQR 687 ± 248 784 ± 246 0.192 1.3 ± 0.3 1.9 ± 0.8 0.004
Coefficient of Variation (%) 8.2 ± 2.4 9.5 ± 2.3 0.054 8.0 ± 2.3 10.2 ± 3.2 0.014
Average Real Variability 271 ± 87 413 ± 154 0.001 0.5 ± 0.2 1.0 ± 0.6 <0.001
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Values are mean ± SD. WH, Non-Hispanic White men (n=21); BL, Non-Hispanic Black men (n=24); IQR, Interquartile Range.

Figure 2.

Figure 2.

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Histogram analysis of cardiac output (CO; Fig. 2A) and total peripheral resistance (TPR; Fig. 2B) in Non-Hispanic Black (BL; n=24, red bars) and Non-Hispanic White (WH; n=21, blue bars) men. Areas of the histogram wherein both WH and BL men exhibit cardiac cycles (i.e., overlap) are denoted in purple. Data represent CO values binned in increments of 100mL/min, and TPR binned in 0.2 mmHg/L/min increments away from the mean respective values. For statistical analysis and because of the markedly different range in values between WH and BL men, a sliding bin scale was used to normalize all histograms to 17 bins (see Methods). Dotted lines represent the bounds of each statistical bin. Brackets denote areas of the histogram where there is a significant difference (P<0.05) for all bins within that bracket between BL men and WH men.

Spontaneous BRS

Figure 3 shows spontaneous cardiac BRS (Fig. 3A; left panel), and spontaneous sympathetic BRS (Fig. 3B; left panel) in BL men compared to WH men. BL men exhibited significantly greater cardiac BRS compared to WH men. Conversely, BL men exhibited significantly reduced sympathetic BRS relative to WH men. Interestingly, in this cohort of young healthy men cardiac BRS demonstrated no significant relationship to MAP SD, an index of BP variability (Fig. 3A; right panel). In contrast, sympathetic BRS provided a significant relationship to MAP SD, indicating that lower sympathetic BRS correlated with greater BP variability (Fig. 3B; right panel). Similar results were found when relationships were performed with SBP or DBP (data not shown).

Figure 3.

Figure 3.

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Mean summary data for spontaneous cardiac baroreflex sensitivity (BRS; Fig. 3A, left panel) and spontaneous sympathetic BRS (Fig. 3B; left panel) in Non-Hispanic Black (BL; black bars and circles) and Non-Hispanic White (WH; open bars and circles) men. The right panels depict the correlations between cardiac (Fig. 3A, right panel) and sympathetic (Fig. 3B, right panel) BRS, and mean arterial pressure (MAP) standard deviation (SD), as an index of blood pressure (BP) variability. Bar graph data are presented as mean ± SD, with N=24 BL men and N=21 WH men for cardiac BRS, and N=15 BL men and N=15 WH men for sympathetic BRS. Correlations use the same number of individuals. *P<0.05 BL men versus WH men.

DISCUSSION

The major novel findings of the present investigation are three-fold. First, we have demonstrated, for the first time, that young healthy BL men exhibited greater resting beat-to-beat BP variability compared to WH men. Second, this greater BP variability was accompanied by an augmented TPR variability. Third, in this cohort of young, healthy men, reduced sympathetic BRS was related to greater BP variability. These data suggest that an augmented beat-to-beat variability in TPR may underlie an augmented beat-to-beat BP variability in BL men, and that reductions in sympathetic BRS might also be involved. Collectively, these findings provide novel insight into resting BP dynamics in young, healthy BL men. Notably, despite a normal, and similar, resting mean BP compared to WH men, the BL men exhibited considerably greater beat-to-beat BP and TPR variability. These swings in BP over time may contribute to the enhanced cardiovascular risk profile in BL individuals.

Recent studies suggest that an augmented short-term BP variability is associated with the development, progression, and severity of cardiovascular and renal disease (Parati, Ochoa, & Bilo, 2012). Moreover, resting beat-to-beat BP variability has been shown to be markedly augmented in patients with HTN (Xia et al., 2017). Furthermore, in these patients, greater short-term SBP variability is correlated with increased left ventricular mass and intima-media thickness (Tatasciore et al., 2007), suggesting that short-term BP variability may provide a stimulus for structural remodeling of the heart and vasculature. Thus, our findings could represent an early pre-clinical manifestation of a BP variability phenotype in BL men which may predispose these individuals to future cardiovascular and renal disease. Additional prospective follow-up studies are warranted.

Although the mechanisms for this augmented resting BP variability remain incompletely understood, there are several possibilities that warrant discussion. First, it is important to consider the arterial baroreflex given its importance in the regulation of beat-to-beat BP. In this regard, there is some experimental evidence suggesting an impairment in arterial baroreflex control of BP in BL individuals (Holwerda, Fulton, Eubank, & Keller, 2011; Zion et al., 2003). Notably, in our cohort, young BL men exhibited blunted sympathetic BRS compared to WH men. Interestingly, in contrast, BL men demonstrated an augmented cardiac BRS. Despite these apparent differences in cardiac versus sympathetic (peripheral) BRS, only sympathetic BRS correlated with BP variability, wherein reduced sympathetic BRS was associated with an augmented BP variability. These findings are in general agreement with previous studies demonstrating that cardiac responses contribute only minimally to the baroreflex-mediated BP response (Ogoh et al., 2002; Ogoh et al., 2003). Thus, it may not be surprising that even in the presence of greater cardiac BRS, an augmented BP variability phenotype seemed to be present in the BL men. However, the blunted sympathetic BRS in BL men documented herein is not a universal finding. Fonkoue et al. (Fonkoue, Schwartz, Wang, & Carter, 2018) previously observed no difference in sympathetic BRS between WH and BL men, which may indicate that additional mechanisms beyond blunted sympathetic BRS also contribute to this augmented BP variability. In this regard, given our data identifying augmented TPR variability in BL individuals, it is plausible that other changes in the peripheral vasculature, independent of arterial baroreflex control of MSNA, may contribute to the augmented BP variability. Accordingly, a number of investigations have documented blunted endothelial-dependent vasodilation in response to a variety of pharmacological and physiological stimuli (Brothers et al., 2019; Stein et al., 1997; Stein et al., 2000) in young, healthy BL individuals. Likewise, there may also be an augmented endothelium-mediated vasoconstriction via greater concentrations of circulating endothelin-1 in BL individuals (Treiber et al., 2000). Finally, our laboratory recently documented exaggerated vasoconstriction in response to spontaneous bursts of MSNA (Vranish et al., 2018), suggesting augmented sympathetically-mediated vasoconstriction in BL men under resting conditions. This data is consistent with the heightened vasoconstriction following intra-arterial infusion of the α1-adrenergic agonist phenylephrine in BL compared to WH individuals (Stein et al., 2000). Collectively, these data suggest alterations in vascular responsiveness (Brothers et al., 2019; Stein et al., 1997; Stein et al., 2000; Vranish et al., 2018) in this population that may contribute to the greater beat-to-beat BP variability. Nonetheless, a greater understanding of the underlying mechanisms contributing to this augmented BP variability phenotype will be an important next step to provide further insight into the modifiers/determinants of enhanced cardiovascular risk in the BL population.

Perspectives and Significance

An augmented resting beat-to-beat BP variability may represent a potential mechanism by which BL men are predisposed to the development of HTN earlier in life, thus augmenting their cardiovascular risk profile. This notion is supported by previous work, wherein an augmented BP variability in youth was associated with the development of HTN as an adult (Chen, Srinivasan, Ruan, Mei, & Berenson, 2011). Interestingly, the magnitude of augmentation in beat-to-beat BP variability we found in BL versus WH men is similar to the disparity which has been previously reported between patients with HTN and control subjects (Xia et al., 2017). Indeed, despite similar resting mean BPs between groups, the young BL men in the present investigation exhibited a potent BP variability phenotype, that was similar to patients with HTN. Even more striking, is the notion that this magnitude of BP variability was present on a time scale that would be representative of the time frame between ambulatory BP measurements (i.e., within 20-minutes) suggesting that this level of variability may not be detected by either traditional clinic/office BP monitoring or by ambulatory BP monitoring.

There are some considerations for the present study that warrant discussion. First, we did not perform ambulatory BP monitoring, and thus we were unable to assess the possibility of masked hypertension in this study cohort. Future studies should incorporate both ambulatory BP and beat-to-beat measures to further probe the significance of this BP variability phenotype in young, healthy BL men. Second, given that the current study only included men, caution is warranted in extrapolating these findings to women.

In summary, we document for the first time, an augmented beat-to-beat BP variability in young, healthy BL men at rest, which was accompanied by augmented TPR variability. This BP variability phenotype may contribute importantly to the enhanced cardiovascular risk profile seen in BL men.

New Findings.

What is the central question of the study?

The prevalence of hypertension in Black individuals exceeds other racial groups. Despite this well-known heightened risk, the underlying contributing factors remain incompletely understood. Herein, we hypothesized young black men would exhibit augmented beat-to-beat blood pressure variability compared to white men. Furthermore, we hypothesized black men would exhibit augmented total peripheral resistance variability.

What is the main finding and its importance?

We demonstrate that young, healthy black men exhibit greater resting beat-to-beat blood pressure variability compared to their white counterparts, which is accompanied by greater variability in total peripheral resistance. These swings in blood pressure over time may contribute to the enhanced cardiovascular risk profile in black individuals.

ACKNOWLEDGEMENTS

We wish to thank the participants for their time and effort.

SOURCES OF FUNDING

This work was supported by the National Heart, Lung, and Blood Institute HL-130906 (to D.M.K.), an American College of Sports Medicine Doctoral Student Foundation Grant (to B.E.Y.), and The University of Texas at Arlington College of Nursing and Health Innovation. P.J.F. is supported by NIH R01 HL127071. B.E.Y. is supported by an American Heart Association Pre-Doctoral Fellowship (19PRE34380596).

Footnotes

DISCLOSURES

The authors have no disclosures to report.

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