In this study, we evaluated a healthy cohort of endurance-trained athletes to identify a sub-population with hypertension using gold-standard ambulatory blood pressure monitoring (24-h ABPM). We then sought to determine the diagnostic accuracy of four candidate exercise BP metrics and hypothesised that workload-indexed metrics would provide greater diagnostic accuracy for the diagnosis of hypertension in athletes than a single SBPmax cut-off to define EEBP.
We recruited a sub-population from two ongoing prospective studies involving cardiovascular assessment in endurance athletes. The Pro@Heart study: 'the prospective athlete heart study - elucidating genetic determinants of cardiac remodelling using exercise as an environmental stress', and the ProAFHeart study: 'atrial remodelling and the risk of arrhythmias in endurance athletes'. The Pro@Heart study protocol has been described previously [19], with identical procedures used for the ProAFHeart study. Research protocols received approval from the Alfred Hospital Ethics Committee, Melbourne, Australia (333/15, 484/16, respectively). All participants provided written informed consent.
Participants were endurance-trained individuals, ranging from recreationally active to highly trained national level athletes [20], aged 16-80 years. Participants who underwent detailed fitness and cardiac evaluation between February 2018 and December 2022 at the Baker Heart and Diabetes Institute (Melbourne, Australia) were invited to undergo additional 24-h ABPM at a later date to assess for hypertension as part of an extended evaluation protocol.
Participants were administered a questionnaire addressing cardiovascular risk factors, sporting and exercise history, and medications at the time of their study evaluation.
Resting office BP was recorded at the baseline visit as a single measurement in the supine position after 5-10 min of rest. A digital automatic BP machine (Omron HEM-907XL Pro Blood Pressure Monitor, Kyoto, Japan) and an appropriately sized cuff were used. Participants were classified as having office hypertension if SBP was ≥140 mmHg and/or diastolic BP (DBP) was ≥90 mmHg [2]. Resting heart rate was taken from a resting 12-lead electrocardiogram (ECG).
A maximal cardiopulmonary exercise test (CPET) was conducted on an electronically braked bicycle ergometer (LODE Excalibur sport, Groningen, The Netherlands) for the determination of exercise BP metrics and cardiorespiratory fitness. Two minutes of passive resting data seated on the bike were obtained, after which the participants performed a 1 min warm-up at 50 Watts. Thereafter, the workload increased progressively at a rate of 30 Watts/min until volitional fatigue. The peak power output (Watts) achieved was defined as the maximal workload. The peak heart rate achieved during exercise was obtained from a continuous 12-lead ECG. Continuous gas exchange data were collected using a calibrated metabolic cart (Vyntus CPX Metabolic Cart, Vyaire Medical, GmbH, Germany) for the measurement of peak oxygen uptake (O), calculated as the highest value from a 30 sec rolling average, using 5 sec averaged breath-by-breath values. Percentage of predicted O was calculated using the FRIEND equation [21].
The BP response during the CPET was measured using a validated automated BP machine that uses R-wave gating from a 3-lead ECG and a brachial microphone for Korotkoff-sound detection (Tango® M2 ECG-gated automated BP monitor, Suntech Medical Inc, NC, USA) [22]. BP was measured seated at rest on the bike (pre-exercise BP), every 2 min throughout the test, and every minute during the recovery phase. SBP was defined as the highest SBP during the exercise test and the corresponding DBP as the maximal DBP (DBP). EEBP based on SBP was defined as SBP ≥ 220 mmHg in males and ≥200 mmHg in females based on reference values for athletic individuals [12].
To define the relationship between SBP and exercise workload, the corresponding workload was recorded with each SBP measurement. The SBP/W-slope was defined as the slope of the linear regression for each individual, with SBP plotted against workload, as previously reported by our group [14]. The last measured SBP during exercise (as a single value) was indexed to the corresponding workload to obtain the SBP/W-ratio. Submaximal SBP was assessed at a power output of 2 Watts/kg (mean 2.0 ± 0.2 Watts). The intensity of 2 Watts/kg was chosen as an arbitrary workload corresponding to a mild/moderate intensity of exercise in an athletic population. Optimal cut-off values to define EEBP for all three workload-indexed BP metrics were obtained from the highest Youden's index value from receiver operating characteristic(ROC) curve analysis.
The median follow-up time between the CPET and 24-h ABPM was 17 [IQR: 9 - 22] months. The 24-h ABPM was performed using a Spacelabs Ontrak device (Spacelabs Healthcare, WA, USA), and 98% of participants had a minimum of 70% of successful readings (mean successful readings 93 ± 7%). After ensuring appropriate cuff size, inflation intervals were set to every 20 min during the day and every 30 min at night. Participants were instructed to remain still and refrain from speaking during measurements, continue daily activities while avoiding exercise, and record their activity, wake-up, and sleep times in a diary. These times were adjusted in the system prior to analysis to ensure accurate daytime and nighttime BP measurements. Hypertension on ABPM was defined as a mean 24-h BP ≥ 130/80 mmHg and/or mean daytime BP ≥ 135/85 mmHg and/or mean nighttime BP ≥ 120/70 mmHg [2]. The ABPM data were analysed using an in-house program (ABMA 2008 system) developed at the Baker Heart and Diabetes Institute (Melbourne, Australia).
Participants underwent a fasting blood test at their baseline evaluation prior to exercise testing, which was immediately analysed for serum creatinine, estimated glomerular filtration rate (eGFR), and lipid profile to assess kidney function and hypercholesterolemia as potential risk factors for hypertension.
Statistical analysis was conducted using SPSS software version 30.0 (SPSS Inc., IBM Inc., Chicago, Illinois, USA). Variables were assessed for normality using the Shapiro-Wilk test. Continuous data are presented as mean ± standard deviation (SD) or median (interquartile range [IQR]) and categorical variables as numbers and percentages. Receiver operating characteristic (ROC) curve analysis was performed for all four exercise BP metrics. For the workload-indexed metrics without established thresholds, Youden's Index was used to identify optimal cut-off values. The area under the curve (AUC) was calculated for each ROC, and comparisons between ROC curves were performed using the DeLong test. To evaluate the diagnostic accuracy of each exercise BP metric and its corresponding EEBP definition, sensitivity, specificity, and positive and negative predictive values were calculated, determined from the number of athletes classified as hypertensive and normotensive by 24-h ABPM (Supplementary Table S1). Binary linear regression analyses were done to evaluate the independent associations of age and sex with each EEBP definition. We acknowledge that the relatively small number of females in our sample (n = 18 vs. 36 males) limits the precision of sex-specific estimates. A p-value < 0.05 (two-tailed) was considered statistically significant. Figures were created using GraphPad Prism 8.0.1 (San Diego, CA, USA).