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Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Division of Cardiology, Massachusetts General Hospital, Boston, MassachusettsCardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts
Change in SBP (ΔSBP) with exercise was significantly correlated with unadjusted change in (Δ, in L/min) in athlete patients undergoing CPET.
•
Despite lower peak exercise SBP and ΔSBP than male athletes, female athletes had paradoxically higher ΔSBP/ unadjusted Δ (and ΔSBP/ Watts for cycle tests). The physiologic mechanism of this finding is unclear, and future work is needed to define whether this indicates sex-based differences in the systemic vascular response to exercise.
•
The previously defined “normal” SBP response of 10 mmHg/MET, derived from studies using estimated rather than measured METs, overestimated by approximately two fold the observed value in this athletic cohort (5-6 mmHg/ measured MET). Our results provide a more appropriate estimate for normal exercise SBP in athletes referred for clinical exercise testing.
Abstract
Purpose
Although exercise testing guidelines define cutoffs for an exaggerated exercise systolic blood pressure (SBP) response, SBPs above these cutoffs are not uncommon in athletes given their high exercise capacity. Alternately, guidelines also specify a normal SBP response that accounts for metabolic equivalents (METs; mean [SD] of 10 [2] mm Hg per MET or 3.5 mL/kg/min oxygen consumption []). SBP and increase less during exercise in females than males. It is not clear if sex-based differences in exercise SBP are related to differences in or if current recommendations for normal increase in SBP per MET produce reasonable estimates using measured METs (ie, ) in athletes. We therefore examined sex-based differences in exercise SBP indexed to in athletes with the goal of defining normative values for exercise SBP that account for fitness and sex.
Methods
Using prospectively collected data from a single sports cardiology program, normotensive athlete patients were identified who had no relevant cardiopulmonary disease and had undergone cardiopulmonary exercise testing with cycle ergometry or treadmill. The relationship between ΔSBP (peak – rest) and Δ (peak – rest) was examined in the total cohort and compared between sexes.
Findings
A total of 413 athletes (mean [SD] age, 35.5 [14] years; 38% female; mean [SD] peak , 46.0 [10.2] mL/kg/min, 127% [27%] predicted) met the inclusion criteria. The ΔSBP correlated with unadjusted Δ (cycle: R2 = 0.18, treadmill: R2 = 0.12; P < 0.0001). Female athletes had lower mean (SD) peak SBP (cycle: 161 [15] vs 186 [24] mm Hg; treadmill: 165 [17] vs 180 [20] mm Hg; P < 0.05) than male athletes. Despite lower peak SBP, mean (SD) ΔSBP relative to unadjusted Δ was higher in female than male athletes (cycle: 25.6 [7.2] vs 21.1 [7.3] mm Hg/L/min; treadmill: 21.6 [7.2] vs 17.0 [6.2] mm Hg/L/min; P < 0.05). When was adjusted for body size and converted to METs, female and male athletes had similar mean (SD) ΔSBP /ΔMET (cycle: 6.0 [2.1] vs 5.8 [2.0] mm Hg/mL/kg/min; treadmill: 4.7 [1.8] vs 4.8 [1.7] mm Hg/mL/kg/min).
Implications
In this cohort of athletes without known cardiopulmonary disease, observed sex-based differences in peak exercise SBP were in part related to the differences in Δ between male and female athletes. Despite lower peak SBP, ΔSBP/unadjusted Δ was paradoxically higher in female athletes. Future work should define whether this finding reflects sex-based differences in the peripheral vascular response to exercise. In this athletic cohort, ΔSBP/ΔMET was similar between sexes and much lower than the ratio that has been proposed by guidelines to define a normal SBP response. Our observed ΔSBP/ΔMET, based on measured rather than estimated METs, provides a clinically useful estimate for normal peak SBP range in athletes.
Blood pressure (BP) is assessed routinely as part of clinically indicated exercise testing. Contemporary guidelines most commonly define an exaggerated BP response with sex-based cutoff values (SBP >210 mm Hg for males and >190 mm Hg in females),
Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: a systematic review and meta-analysis.
Impact of exaggerated blood pressure response in normotensive individuals on future hypertension and prognosis: Systematic review according to PRISMA guideline.
Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Journal of the American College of Cardiology.2017; 71: 1269-1324
2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH).
The use of single, sex-specific absolute cutoff values to define a normal exercise systolic BP (SBP) response fails to account for basic exercise physiology, which obligates that SBP increases during exercise as the stroke volume ejected during each cardiac cycle increases.
but specific cutoffs for normal exercise SBP do not reflect this variation. Indeed, peak exercise SBPs in highly fit individuals are higher than in untrained individuals
and occasionally above guideline-specified cutoff values with unclear relevance.
Alternately, guidelines specific to cardiopulmonary exercise testing (CPET) recommend a normal range of SBP response that accounts for achieved metabolic equivalents (METs; mean [SD], 10 [2] mm Hg per MET or 3.5 mL/kg/min oxygen consumption []).
having lower peak SBP and than males. Although others have examined how observed sex-based differences in exercise SBP relate to lower achieved workload or METs in females versus males,
Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.
European Journal of Applied Physiology.2021; 121: 1859-1869
no prior work has examined this issue in an athletic cohort using measured () rather than estimated METs. In addition, it remains unclear whether current guideline recommendations for normal change in SBP relative to METs produce reasonable estimates for exercise SBP using measured METs in athletes.
We therefore performed this study to evaluate sex-based differences among athletes in the relationship between exercise SBP and exercise , with a hypothesis that a differential increase in SBP between the sexes would be related to . In this process, we sought to define normative values for exercise SBP indexed to and METs that account for exercise capacity and sex in athletes. In addition, we sought to define how exercise SBP relative to varied as a function of increasing age. To accomplish these goals, we examined the relationship between change in SBP and change in from rest to peak exercise in normotensive athletic patients who underwent CPET in a single, high-volume exercise laboratory.
Methods
Study Population
Participants were eligible for inclusion in this study if they were ≥18 years of age and performed CPET on the treadmill or cycle ergometer in the exercise laboratory of the Massachusetts General Hospital Cardiovascular Performance Program. The Cardiovascular Performance Program provides clinical cardiovascular care to physically active individuals, and patients undergo a standardized maximal effort–limited CPET on referral unless clinically contraindicated. From exercise laboratory opening (October 1, 2011) through April 27, 2021, CPET results were prospectively collected in a research database. Rigorous clinical exclusion criteria (Supplemental Table 1) derived from the CPET itself, the medical history including diagnoses made as a result of the CPET, and diagnostic testing (Eg, transthoracic echocardiography) were used to generate a cohort that was free of clinically evident cardiovascular or pulmonary disease (Figure 1). Specifically, we excluded athletes with a suspected or established history of genetic, infiltrative, congenital, toxic, and idiopathic myocardial disease, clinically relevant tachyarrhythmia or bradyarrhythmia, obstructive epicardial coronary artery disease, valvular heart disease greater than mild severity, familial or idiopathic thoracic aortic disease, venous thromboembolic disease, pulmonary hypertension, and prior stroke. Athletes taking medications with a possible or definitive negative chronotropic mechanism of action, including β-blockers, nondihydropyridine calcium channel blockers, and class 1 or 3 antiarrhythmic agents, were excluded. Participants with ischemic ECG changes or evidence of clinically relevant arrhythmia during the CPET were excluded. All athletes with a prior history of hypertension, taking medications with impact on BP, or with a resting SBP ≥140 mm Hg or diastolic BP ≥90 mm Hg documented on the day of the CPET were also excluded. A signficant minority of athletic patients who underwent comprehensive clinical evaluation in the Cardiovascular Performance Program were free of clinically relevant pathologic findings; this group constitutes the cohort that was analyzed for this study.
Athletes were defined as individuals who participate in an organized individual or team sport that requires regular exercise training and who place a high premium on athletic achievement.
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 1: classification of sports: dynamic, static, and impact.
Endurance athletes were defined as those practicing the following primary sport disciplines: long distance running, cycling, triathlon, rowing, and/or swimming. Team sport and recreational athletes were defined as those not participating in the above endurance sports (see Supplemental Table II for full distribution of sports). All aspects of this study were approved by the Mass General Brigham Human Research Committee (Boston, Massachusetts).
Cardiopulmonary Exercise Testing
All participants underwent an intensity-graded, maximal effort–limited exercise test on either the treadmill (Woodway Pro 27, Woodway USA, Waukesha, Wisconsin) or the upright cycle ergometer (Sport Excalibur Bicycle Ergometer, Lode, Holland) with continuous gas exchange monitoring. The exercise modality was chosen by the participant and exercise physiologist with the goal of matching testing to a participant's primary form of exercise. The cycle ergometry test protocol consisted of 3 minutes of free-wheel cycling followed by continual increase in resistance (varying from 10 to 40 W/min) until test completion. Treadmill test exercise began with a 5- to 10-minute warmup at 3.0 to 7.5 miles per hour and 1% grade followed by a progressive increase in incline (0.5% grade increase every 15 seconds) at a fixed speed until exhaustion. The intensity of the cycle ergometry ramp and the speed of treadmill testing were determined by the overseeing exercise physiologist in conjunction with the participant with a goal of reaching a 10-minute total ramp time. The peak respiratory exchange ratio was defined as exhaled carbon dioxide divided by oxygen consumption using the same 30-second mean. Test termination was determined by volitional exhaustion, and maximal effort was confirmed by a peak respiratory exchange ratio >1.05 and a maximal heart rate of >80% age- and sex-based predicted peak values. Gas exchange was measured on a breath-by-breath basis using a Hans Rudolph V2 Mask (Hans Rudolph Inc, Shawnee, Kansas) and a commercially available metabolic cart and gas exchange analyzer (Ultima CardiaO2; Medgraphics Diagnostics, St Paul, Minnesota) and analyzed using Breeze Suite software version 8.2 (Medgraphics Diagnostics). Continuous 12-lead ECG monitoring (X12+ wireless ECG transmitter, Mortara Instrument, Milwaukee, Wisconsin) was performed during all testing.
A manual sphygmomanometer was used to measure BPs. All protocols included 3 minutes of quiet rest on the exercise apparatus before exercise. Resting BP was obtained before exercise during the final 30 seconds of resting gas exchange measurement. Resting was defined as the mean oxygen uptake during the same final 30 seconds of rest. Peak exercise BP was obtained at or immediately after (completed within 15 seconds) the effort limited exercise effort.
Peak was defined as the highest mean oxygen uptake for a period of 30 seconds during the last minute of effort limited exercise. was assessed unadjusted (u)and adjusted (a) for body mass. ΔSBP was defined as peak SBP minus resting SBP, and Δ was defined as peak minus resting .
Statistical Analysis
Descriptive continuous variables are presented as mean (SD) or median (interquartile range) as appropriate and were compared between groups using a 2-sample unpaired t test or Wilcoxon rank sum test, respectively. Categorical variables are presented as number (percentage) and compared by the χ2 test or Fisher exact test when the sample size was ≤5 per category. Pearson correlation was used to assess the relationship between ΔSBP and Δ. Multivariate linear regression was used to examine the relationship between ΔSBP/Δ and demographic characteristics (sex and age). Statistical analyses were performed using R software (R Core Team, Vienna, Austria), and figures were generated using GraphPad Prism software, version 7.0 (GraphPad Inc, San Diego, California). P < 0.05 was considered significant for all analyses.
Results
Among 1837 patients who were referred for clinically indicated CPET, only 413 athlete patients (22%) met study inclusion criteria that indicated they were free of clinically evident cardiopulmonary disease (Figure 1). Baseline characteristics are presented in Table 1. The mean (SD) age of the cohort was 35.5 (14) years and there was a high proportion of white participants (92%). Female participants constituted 38% of the total cohort and were younger, with smaller weight, height, and body mass index. Although half of the male participants completed the CPET on the treadmill and half on the cycle ergometer (cycle), a higher proportion of female participants (68%) completed the test on the treadmill. There were 27 distinct primary sporting disciplines represented by athletes in this cohort, with the most common being running (23%), multiple sports (14%), cycling (11%) and triathlon (11%) (Supplemental Table II).
CPET characteristics stratified by sex and exercise modality are given in Table 2. Between cycle and treadmill tests, expected differences were found in key parameters, such as peak , which was higher on treadmill tests. All further analysis was performed separately for tests performed on the two modalities. Peak was supranormal (cycle: 123% [30%] predicted; treadmill: 131% [23%] predicted) and did not significantly differ between sexes when assessed as a percent predicted. Measured peak u was lower in female participants (2.34 [0.48] vs 3.64 [0.74] L/min for cycle; 2.81 [0.51] vs 3.99 [0.61] L/min for treadmill) as was a (36.9 [8.0] vs 45.6 [10.2] mL/kg/min for cycle; 45.0 [8.5] vs 50.9 [9.3] mL/kg/min for treadmill; 10.5 [2.3] vs 13.0 [3.1] METs for cycle; 12.9 [2.4] vs 14.6 [2.7] METs for treadmill [1 MET = 3.5 mL/kg/min ]). For cycle tests, peak workload was lower in female than male participants (211 [48] vs 344 [72] W; P < 0.05).
Table 2Cardiopulmonary exercise test characteristics.
Compared with male participants, female participants had lower mean resting SBP (110 [10] vs 121 [9] mm Hg for cycle; 113 [11] vs 121 [10] mm Hg for treadmill) and diastolic BP (71 [8] vs 78 [7] mm Hg for cycle; 73 [9] vs 76 [8] mm Hg for treadmill). Female participants also had lower peak SBPs (161 [15] vs 186 [24] mm Hg for cycle; 165 [17] vs 180 [20] mm Hg for treadmill) than male participants, with smaller change from rest to peak (ΔSBP: 51 [13] mm Hg [47% (13%)] vs 66 [23] mm Hg [56% (18%)] for cycle; 52 [14] mmHg [47% (14%)] vs 60 [19] mm Hg [50% (17%)] for treadmill). A total of 9 of 155 female athletes (5.8%) and 27 of 258 male athletes (10.5%) met guideline-based cutoff criteria for an exaggerated BP response to exercise (SBP >190 mm Hg for female participants; SBP >210 mm Hg for male athletes). In contrast, using the alternate guideline-recommended normal SBP response of Δ10 (2) mm Hg/MET, no athletes exceeded the upper limit (12 mm Hg/MET), only 4 of 155 female athletes (3%) and 15 of 258 male athletes (6%) had SBPs within the recommended reference range (Δ8–12 mm Hg/MET), and the SBPs of all others fell below this range. The estimate of 10 mm Hg/MET for a normal response produced expected SBPs that far exceeded observed SBPs in all groups (expected peak SBPs: 250 [31] mm Hg for male participants on cycle, 217 [23] mm Hg for female participants on cycle, 266 [26] mm Hg for male participants on treadmill, 241 [25] mm Hg for females on treadmill; all P < 0.001 for comparison to observed peak SBPs).
When assessing the relationship between ΔSBP and Δ (Figure 2), we found a greater correlation between ΔSBP and Δ for tests performed on the cycle (R2 = 0.18, P < 0.001 for Δ in L/min; R2 = 0.12, P < 0.001 for Δ in mL/kg/min) (Figures 2A and 2C) versus those on the treadmill (R2 = 0.04, P < 0.01 for Δ in L/min; R2 = 0.0003, P = 0.80 for Δ in mL/kg/min) (Figures 2B and 2D). When Δ was left unadjusted for body mass (uVO2 in L/min) the correlation between ΔSBP and Δ was greater than when it was adjusted (aΔV̇O2 in mL/kg/min) within each exercise test modality type.
Figure 2Difference between peak and rest systolic blood pressure (ΔSBP) versus difference between peak and rest oxygen uptake (ΔV̇o2) for cycle ergometry and treadmill testing. Panels A. and C.show athletes undergoing cycle ergometry (n = 180). Panels B. and D. showathletes undergoing treadmill testing (n = 233). Linear regression lines and equations for ΔSBP as dependent variable and ΔV̇o2 as the independent variable are shown.
The ΔSBP indexed to Δ, ΔMETs, and workload (in Watts) by exercise test modality and sex are given in Table 2 and Figure 3. There was a higher ΔSBP/Δ on cycle tests (+4.0 mmHg/L/min, +0.34 mm Hg/mL/kg/min, and +1.2 mmHg/MET vs treadmill), which was consistent with a higher amount of isometric stress inherent to cycling exercise.
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 1: classification of sports: dynamic, static, and impact.
Despite lower exercise SBP and ΔSBP, female participants had significantly higher ΔSBP/uΔ than male participants (25.6 [7.2] vs 21.1 [7.3] mm Hg/L/min for cycle; 21.6 [7.2] vs 17.0 [6.2] mm Hg/L/min for treadmill) (Figures 3A and 3B). On cycle tests, female participants also had higher ΔSBP/work compared with male participants (0.25 [0.08] mmHg/W vs 0.20 [0.06] mmHg/W; P < 0.05). In contrast, when was adjusted for body size, female and male participants had similar ΔSBP/aΔ (1.67 [0.57] vs 1.71 [0.59] mmHg/mL/kg/min for cycle; 1.36 [0.52] vs 1.35 [0.52] mmHg/mL/kg/min for treadmill) (Figures 3C and 3D). When a was expressed in METs, female and male participants also had a similar ΔSBP/ΔMET (cycle: 5.8 [2.0] vs 6.0 [2.1] mm Hg/mL/kg/min; treadmill: 4.8 [1.7] vs 4.7 [1.8] mm Hg/mL/kg/min). The presence or lack of statistical significance of these key results (ΔSBP/Δ or ΔMET by sex) remained the same when adjusted for slightly differing age in the groups. These key results were also similar when evaluated in the subgroup of endurance sport athletes (Supplemental Table III).
Figure 3Difference between peak and rest systolic blood pressure (ΔSBP)/difference between peak and rest oxygen uptake (ΔV̇o2) by sex for cycle ergometry and treadmill testing. PanelsA. and C. show athletes undergoing cycle ergometry (n = 180). Panels B. and D. show athletes undergoing treadmill testing (n = 233). ΔSBP/ΔV̇O2 in liters per minute was significantly higher (P < 0.001) for females than males for both test types. Dots represent all individual data points. Bars represent the mean and SD.
Assessment of ΔSBP/Δ across the spectrum of age in the study revealed that ΔSBP/Δ was higher with older age and more evident when ΔSBP/uΔ rather than ΔSBP/aΔ was used (Figure 4). The ΔSBP/uΔ increased by 1.0 mm Hg/L/min every 10 years for cycle tests and 1.4 mm Hg/L/min every 10 years for treadmill tests. Female participants had higher ΔSBP/uΔ across the age span, without any difference in the rate of increase in ΔSBP/uΔ with age (nonsignificant age × sex interaction term).
Figure 4Age impact on ifference between peak and rest systolic blood pressure (ΔSBP)/difference between peak and rest unadjusted oxygen uptake (ΔV̇o2). Linear regression lines for ΔSBP/unadjusted ΔV̇o2 as dependent variable and age as the independent variable are shown by sex.
This study sought to evaluate the relationship between the increase in SBP and the increase in with exercise in a population of normotensive athletes free of clinically evident cardiovascular disease who were referred for clinical CPET. Key findings are summarized as follows. First, Δ described a small but statistically significant proportion of the variability in ΔSBP only when Δ was unadjusted for body size and more so on cycle rather than treadmill tests. Despite this significant correlation, the range of ΔSBP at any given Δ remained wide in this athlete population, suggesting other important contributions to ΔSBP. Indeed, we found a small but significant increase in the ΔSBP/Δ ratio with advancing age. Second, although female athletes had lower peak exercise SBP and ΔSBP in this study, they had paradoxically higher ΔSBP/unadjusted Δ and ΔSBP/workload. Third, ΔSBP/aΔ and equivalent ΔSBP/ΔMET were similar in both sexes (5–6 mm Hg/METs) and approximately half of what has previously been described as a normal SBP response in the general population. This result provides a practical metric for application in exercise tests that do not include gas exchange. Overall, our findings suggest that the SBP response to exercise remains variable even after accounting for the factors examined in this study (exercise capacity, workload, sex, and age), with future work needed to further refine its determinants and the optimal SBP metric for prediction of important cardiovascular outcomes.
Although the most commonly applied exercise testing guidelines stipulate sex-based absolute cutoff values for normal peak SBP,
these are not universally used. European guidelines regarding hypertension management state that there is no consensus regarding a normal exercise BP response, and the equivalent US guidelines do not mention exercise BP at all.
Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Journal of the American College of Cardiology.2017; 71: 1269-1324
2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH).
A potential pitfall of SBP cutoff values for prognostication is that they do not address the complex relationships among SBP, exercise capacity, cardiovascular events, and mortality. CPET-specific guidelines from the American Heart Association and American College of Sports Medicine recognize the potential impact of exercise capacity on SBP increase and alternately define a normal BP response to exercise relative to the number of METs achieved.
The recommended ratio (ΔSBP of 10 [2] mm Hg per 1 MET or Δ of 3.5 mL/kg/min) is based on a small study published in a 1973 textbook of healthy males (unknown age and demographic characteristics).
Applying this ratio to the fit athletes who achieved high METs during exercise in this study produces estimates for normal exercise BP that far exceed that observed in most people. To our knowledge, this study is the first to use measured METs rather than METs estimated from standard exercise protocols to assess this relationship in athletes, Our results provide an alternate range of expected ΔSBP/ΔMETs for athletes that is much lower than what is recommended.
Recently, others have evaluated the SBP response to exercise relative to workload or estimated METs on tests that did not use gas exchange, with overall similar results to that of this study. In a large study of male patients in the general population, the median ΔSBP/estimated ΔMETs was 6.2 mmHg/MET on treadmill tests, and a ratio of >10 mmHg/MET, suggested by guidelines
A smaller pair of studies in athletes using estimated METs from cycle tests identified a mean ΔSBP/ΔMETs in a similar range to that of this study that also did not significantly differ by sex (males: n = 47, 5.7 [1.8] mm Hg/MET; females: n = 25, 5.1 [1.6] mm Hg/MET).
Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.
European Journal of Applied Physiology.2021; 121: 1859-1869
Studies in both the general population and in athletes, including the current investigation, have found that the peak exercise SBP and the ΔSBP with exercise are lower in females versus males.
Basic physiology dictates that BP is determined by cardiac output (a cross product of heart rate and stroke volume) and systemic vascular resistance and that uΔ is determined by cardiac output and oxygen extraction, In the present study, ΔSBP/uΔ (and ΔSBP/workload for cycle tests) were paradoxically higher for female versus male athletes. Our finding is similar to that previously found for ΔSBP/workload in nonathlete
Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.
European Journal of Applied Physiology.2021; 121: 1859-1869
cohorts. The relative contributions of sex-based differences in cardiac output, oxygen extraction, and systemic vascular resistance to observed ΔSBP/uΔ were not able to be determined in this study, which did not measure these specific parameters. One prior study in athletes found higher ΔSBP/workload in females despite no significant sex-based differences in resting indexes of vascular function.
Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.
European Journal of Applied Physiology.2021; 121: 1859-1869
Conversely, others have found that the normal exercise-induced reduction in systemic vascular resistance is impaired in older females (+0.8 [1] mmHg/L/min increase in systemic vascular resistance) but similar among young females (−2.8 [0.5] mmHg/L/min decrease in systemic vascular resistance), young males (−1.6 [0.6] mm Hg/L/min), and older males (−3.2 [1.4] mm Hg/L/min).
Although we did not identify any sex-based difference in the rate of increase in ΔSBP/uΔ with age in our study (Figure 4), the potential for higher vascular stiffness in females that may be underappreciated by tracking unindexed SBP during exercise requires further investigation. In particular, future work should continue to examine whether sex-based differences in exercise BP relative to exercise capacity may be attributable to differences between males and females in the response of the β-adrenergic system,
Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.
European Journal of Applied Physiology.2021; 121: 1859-1869
This study has several limitations that warrant further discussion. First, there was no invasive hemodynamic monitoring performed during CPET. Therefore, the relative contributions of changes in cardiac output, peripheral vascular resistance, and oxygen extraction during exercise to the observed ΔSBP/Δ relationships cannot be assessed. In addition, peak BP measurement relied on manual sphygmomanometer and was obtained at or immediately after (completed within 15 seconds) peak exercise to ensure patient tolerability. The challenging nature of obtaining these measurements accurately and securely in athletic patients, particularly on the treadmill, and the potential for a decrement in BP when measurements were obtained immediately after peak exercise may have affected our results. Specifically, these factors may account for the weaker correlation between ΔSBP and Δ for tests performed on the treadmill compared with the cycle. However, we would advocate that our techniques, which balance accuracy and safety in this clinical population, reflect real-world practices in clinical exercise laboratories, particularly those who work with athletic patients. Second, this study contained athletes from a single-center referral population that was primarily white (92%), so future research is needed to assess for differences in more ethnically diverse populations. Third, our cohort was composed of athletes undergoing clinically indicated CPET, thereby raising the possibility of confounding because of occult pathologic findings. However, we excluded athletes (88% of individuals in our database) with relevant medical conditions, including hypertension, that may influence results. Fourth, competition level, training volume, and exercise performance history were not readily available for all athletes in this cohort. In addition, the study cohort size did not permit comparison of the exercise SBP response among sport types. The effect of these parameters on exercise SBP should be considered in future studies.
In conclusion, our results suggest that the change in with exercise helps to account for observed sex-based differences in SBP response to exercise in athletes. Specifically, we observed that ΔSBP/ΔMET was similar between sexes and, at approximately 5 mm Hg/MET for treadmill tests and 6 mm Hg/MET for cycle ergometer tests, was much lower than the ratio that has been proposed by guidelines to define a normal SBP response. Observed ΔSBP/ΔMET in this study provides a clinically useful estimate for normal peak SBP in similar referral populations of athletes. Future work is required to identify the physiologic cause of a paradoxically higher ΔSBP/uΔ and ΔSBP/workload in females and to define whether high SBP relative to in athletes carries the same poor health outcomes as has been suggested by recent research
The authors have no relevant disclosures to this work.
Acknowledgments
Author contributions are as follows: Bradley J. Petek: conceptualization, methodology, formal analysis, investigation, data curation, writing – original draft, writing – review & editing, visualization; Sarah K. Gustus: writing – review & editing, data curation, resources, visualization; Timothy W. Churchill: writing – review & editing, conceptualization; J. Sawalla Guseh: review & editing, conceptualization; Garrett L Loomer - review & editing, data curation; Carolyn VanAtta - review & editing, data curation; Aaron L. Baggish: writing – review & editing, conceptualization, supervision; Meagan M. Wasfy: conceptualization, methodology, formal analysis, writing – original draft, writing – review & editing supervision, visualization, supervision.
Supplementary materials
Table S1Exclusion Criteria for Current Study
Patient Population
1) Non-athletes
2) Pediatric athletes (<18 years old)
3) Rowing ergometry test
4) No clinical evaluation in the CPP clinic or no past medical history available
5) Athletes on negative chronotropic medications (beta-blockers, non-dihydropyridine calcium channel blockers, and Class 1 or 3 anti-arrhythmic agents).
2) Congenital heart disease: atrial septal defect, ventricular septal defect, transposition of the great arteries, Ebstein's anomaly, tetralogy of Fallot, etc.
5) Pulmonary Vascular Disease: venous thromboembolism, pulmonary embolism, right ventricular systolic pressure >40 mmHg on echocardiogram, or known history of pulmonary hypertension
6) Coronary Disease: significant epicardial coronary disease (coronary angiography or coronary computed tomography angiography >50%), prior percutaneous coronary intervention or coronary artery bypass graft, type I non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, anomalous coronary artery
7) Active or prior malignancy: excluding isolated cutaneous malignancies
8) Neurovascular Disease: prior history of stroke or TIA
9) Hypertension
Abnormal CPET Characteristics
10) Resting pulmonary function tests with FEV1 and or FVC <80% predicted
11) Exercise-induced asthma (FEV1 reduced by 10% or more) on post-exercise spirometry
12) Significant arrhythmia during CPET ramp [supraventricular tachycardia, ventricular tachycardia, atrial fibrillation, Mobitz I heart block or higher degree atrioventricular block; isolated pre-ventricular contractions (PVC's) or pre-atrial contractions (PAC's) were allowed]
13) Ischemic electrocardiogram findings during CPET–defined as 1 mm horizontal or downsloping ST-segment depression in 2 or more contiguous leads
14) Respiratory exchange ratio (RER) <1.05
15) Heart rate <80% maximal predicted heart rate
16) Resting systolic BP >140mmHg or diastolic BP >90mmHg
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
ΔSBP/ ΔV̇O2 (mmHg/ml/kg/min)
1.6 (0.5)
1.5 (0.4)
1.3 (0.6)
1.2 (0.4)
ΔSBP/Δ MET (mmHg/ml/kg/min)
5.4 (1.9)
5.2 (1.5)
4.7 (1.9)
4.3 (1.4)
P<0.05 for Cycle Tests in Male Endurance Athletes vs. Female Endurance Athletes, Treadmill Tests in Male Endurance Athlete vs. Female Endurance Athletes
Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: a systematic review and meta-analysis.
Impact of exaggerated blood pressure response in normotensive individuals on future hypertension and prognosis: Systematic review according to PRISMA guideline.
Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Journal of the American College of Cardiology.2017; 71: 1269-1324
2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH).
Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.
European Journal of Applied Physiology.2021; 121: 1859-1869
Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 1: classification of sports: dynamic, static, and impact.
Data are presented as number (percentage) unless indicated.
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