Abstract
ise-induced hypertension (EIH) has increasingly been observed among middle-aged long-distance runners, raising concerns about cardiovascular risk. This study aimed to investigate acute changes in cardiovascular biomarkers associated with vascular inflamma- tion, oxidative stress, antioxidant defense, endothelial function, and myocardial burden in runners with EIH. Thirty-seven middle-aged male runners (aged 40–65 years) were cate- gorized into a normal blood pressure group (NBPG; systolic blood pressure <210 mmHg, n= 23) and an EIH group (EIHG;≥210 mmHg,n= 14) based on maximal systolic blood pressure during a graded exercise test (GXT). Participants performed a 30 min treadmill run at 80% heart rate reserve, and blood samples were collected before
middle-aged male runners (aged 40–65 years) were cate- gorized into a normal blood pressure group (NBPG; systolic blood pressure <210 mmHg, n= 23) and an EIH group (EIHG;≥210 mmHg,n= 14) based on maximal systolic blood pressure during a graded exercise test (GXT). Participants performed a 30 min treadmill run at 80% heart rate reserve, and blood samples were collected before and after exercise. The biomarkers analyzed included high-sensitivity C-reactive protein (hs-CRP), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitric oxide (NO), superoxide dismutase (SOD), and N-terminal pro-brain natriuretic peptide (NT-proBNP). The results show that the EIHG exhibited increased NT-proBNP and SOD levels, along with a reduced NO response, indicating elevated myocardial stress and im- paired vasodilation. hs-CRP was positively correlated with multiple hemodynamic indices, and SOD levels were associated with maximal systolic pressure and myocardial burden. These findings highlight the need for individualized monitoring and cardiovascular risk management in runners with EIH. Keywords:oxidative stress; endothelial dysfunction; myocardial burden; antioxidant enzymes; N-terminal pro-brain natriuretic peptide (NT-proBNP) 1. Introduction Moderate exercise enhances endothelial function, reduces cardiovascular risk, and improves cardiorespiratory fitness, contributing to a better quality of life and a lower Sports2025,13, 195 https://doi.org/10.3390/sports13070195
Sports2025,13, 195 2 of 12 mortality rate [1,2]. However, performing excessive exercise, such as marathon running, may lead to adverse effects, including an increased risk of atrial fibrillation [3], heightened arterial stiffness [4], and a greater prevalence of coronary artery plaques [5]. Excessive exercise can lead to persistently elevated blood pressure, which in turn increases mechan- ical stimulation and oxidative stress within the arteries, accelerating arteriosclerosis [6]. Additionally, high-intensity exercise elevates both volume and pressure within the left ventricle, potentially resulting in left ventricular hypertrophy [7]. In the atrium, fibrosis gradually progresses through atrial dilation, inflammation, and recovery, increasing the risk of fatal arrhythmias such as atrial fibrillation [8]. Recently, the incidence of exercise-induced hypertension (EIH), which refers to an excessive increase in blood pressure during exercise, has been reported to be high among long-distance runners [9]. Runners with EIH are known to have a higher risk of developing arrhythmia [9], a greater prevalence of coronary artery plaques [10], increased expression of cardiac markers [11], and a greater likelihood of ventricular hypertrophy compared to runners with normal blood pressure during exercise [12]. EIH is defined as a systolic blood pressure of≥210 mmHg in men and≥190 mmHg in women during maximal exercise testing [13]. In the general population, EIH is recognized as an independent risk factor for increased cardiovascular disease and mortality [14,15]. While there are no longitudinal studies linking EIH to higher mortality rates in long-distance runners, concerns persist that runners with EIH may face a heightened risk of sudden cardiac death during exercise or competition [16]. The excessive increase in blood pressure during exercise in EIH runners may be attributed to increased afterload, resulting from endothelial dysfunction in peripheral blood vessels induced by excessive exercise [17]. This endothelial dysfunction, along with increased arterial stiffness, is known to enhance sympathetic nervous system activation, further exacerbating the hypertensive response during exercise [15,17]. Although pharmacological treatments such as angiotensin II receptor blockers (ARBs) have shown efficacy in managing EIH, no official treatment guidelines have yet been established [18]. Prolonged exposure to EIH during exercise or competition may lead to a cumulative effect,
along with increased arterial stiffness, is known to enhance sympathetic nervous system activation, further exacerbating the hypertensive response during exercise [15,17]. Although pharmacological treatments such as angiotensin II receptor blockers (ARBs) have shown efficacy in managing EIH, no official treatment guidelines have yet been established [18]. Prolonged exposure to EIH during exercise or competition may lead to a cumulative effect, gradually increasing the likelihood of negative impacts on the heart and blood vessels. This study aims to provide initial evidence on how a single bout of exercise affects biomarkers of vascular inflammation (hs-CRP), oxidative stress (d-ROMs), antioxidant potential (BAP), antioxidant enzyme activity (SOD), vasodilatory function (NO), and myocardial burden (NT-proBNP) in runners with exercise-induced hypertension (EIH). 2. Materials and Methods 2.1. Participants and Study Protocol As outlined in Figure, participants were restricted to middle-aged individuals be- tween the ages of 40 and 65 years. Inclusion criteria required a minimum training history of five years, a training frequency of at least twice per week, and completion of at least five marathons. Of the 43 individuals who applied, 37 completed the full GXT protocol. Although one participant reported lower limb pain, he successfully reached maximal effort during the test and was therefore included in the final analysis. One participant was excluded due to previously undiagnosed hypertension identified during pre-test screening. Additionally, two participants were excluded for engaging in exercise within 24 h prior to testing, and three for alcohol consumption during the same period.
Sports2025,13, 195 3 of 12 Figure 1.The flow chart of the study procedure. GXT: graded exercise testing, NBPG: normal blood pressure group, EIHG: exercise-induced hypertension group. The participants were categorized into two groups based on their maximal systolic blood pressure (SBPmax) during a graded exercise test (GXT); individuals with an SBPmax of <210 mmHg were assigned to the normal blood pressure group (NBPG), and those with SBPmax≥210 mmHg were assigned to the exercise-induced hypertension group (EIHG), following established criteria [13]. All participants completed a 30 min treadmill run at 80% heart rate reserve (HRR). Blood samples were collected immediately before the GXT and immediately after the exercise session. Exercise intensity for each participant was individually prescribed based on the Kar- vonen formula [19], using heart rate reserve (HRR) calculated from the graded exercise test. The target heart rate was determined using the following equation: Target HR = [(HRmax−HRrest)×0.80] + HRrest This study was approved by the Institutional Review Board of Korea National Sport University (Approval No: 20230921-090) and was conducted in accordance with the 1975 Declaration of Helsinki.
Sports2025,13, 195 4 of 12 2.2. Graded Exercise Test A graded exercise test (GXT) was conducted to evaluate the participants’ hemody- namic responses and cardiorespiratory fitness at rest and during exercise. The Bruce protocol was utilized during the test using a treadmill (T170DE, h/p/cosmos, Nussdorf- Traunstein, Germany), with each stage lasting 3 min. At 2 min and 30 s of each stage, heart rate, electrocardiogram (CH2000, Cambridge Heart, Bedford, MA, USA), blood pres- sure (Tango+, SusnTech, Morrisville, NC, USA), respiratory gas analysis (Quark CPET, Cosmed, Rome, Italy), and rating of perceived exertion (Borg scale) were measured. A high-performance microphone was placed in direct contact with the brachial artery to obtain accurate blood pressure readings, while the examiner utilized headphones to en- sure precise measurements. All procedures for the GXT were conducted under American College of Cardiology and American Heart Association guidelines, including criteria for exercise contraindications and termination [20]. The detailed stage-wise structure and measurement schedule of the GXT protocol are presented in Table. Table 1.Graded exercise test protocol used in this study. Stage Time (min) Speed (mph) Grade (%) Measurement Description Rest 0–5 - - HR, SBP, DBP, RPP 5 min seated rest prior to exercise Stage 1 0–3 1.7 10 HR, SBP, DBP, RPE, ECG Measurements taken at 2 min 30 s Stage 2 3–6 2.5 12 HR, SBP, DBP, RPE, ECG Measurements taken at 2 min 30 s Stage 3 6–9 3.4 14 HR, SBP, DBP, RPE, ECG Measurements taken at 2 min 30 s Stage 4 9–12 4.2 16 HR, SBP, DBP, RPE, ECGMeasurements every 30 s Stage 5 12–15 5.0 18 HR, SBP, DBP, RPE, ECGMeasurements every 30 s Stage 6 15–18 5.5 20 HR, SBP, DBP, RPE, ECGMeasurements every 30 s Stage 7 18–21 6.0 22 HR, SBP, DBP, RPE, ECGMeasurements every 30 s Recovery 21–24 1.7 0 HR, SBP, DBP Recovery monitoring during treadmill walking GXT: graded exercise test, Reco: recovery, RPE: rating of perceived exertion, SBP: systolic blood pressure, DBP: diastolic blood pressure, HR: heart rate, ECG: electrocardiography. Note: Blood pressure was monitored using an amplified stethoscope with a high-sensitivity microphone on
6.0 22 HR, SBP, DBP, RPE, ECGMeasurements every 30 s Recovery 21–24 1.7 0 HR, SBP, DBP Recovery monitoring during treadmill walking GXT: graded exercise test, Reco: recovery, RPE: rating of perceived exertion, SBP: systolic blood pressure, DBP: diastolic blood pressure, HR: heart rate, ECG: electrocardiography. Note: Blood pressure was monitored using an amplified stethoscope with a high-sensitivity microphone on the brachial artery. Protocol: Bruce protocol, 3 min per stage. Testing terminated per ACC/AHA guidelines. 2.3. Blood Sampling and Analysis Blood samples were collected from the brachial vein in a fasting state using serum separator tubes (BD Microtainer ® SST™, BD, Franklin Lakes, NJ, USA). After collection, the samples were centrifuged at 3000 rpm for 10 min at 4 ◦ C. The separated serum was aliquoted and stored at−80 ◦ C until further analysis. High-sensitivity C-reactive protein (hs-CRP), an inflammatory biomarker, was mea- sured using the particle-enhanced immunoturbidimetric method on a Cobas 6000/C501 analyzer (Roche Diagnostics, Basel, Switzerland). The coefficient of variation (CV) for hs-CRP was less than 5%. Oxidative stress was assessed using derivatives of reactive oxygen metabolites (d- ROMs), measured by colorimetric analysis with specific reagents (DIA CRON Srl, Grosseto, Italy). Biological antioxidant potential (BAP), representing antioxidant capacity, was also evaluated via the same colorimetric method using the BAP kit (DIA CRON Srl).
Sports2025,13, 195 5 of 12 Nitric oxide (NO), a marker of vascular endothelial function, was determined using a colorimetric assay with reagents from R&D Systems (Minneapolis, MN, USA), and ab- sorbance was measured using a VersaMax Microplate Reader (Molecular Devices, San Jose, CA, USA). Superoxide dismutase (SOD), an endogenous antioxidant enzyme, was analyzed using the Cayman SOD Assay Kit (Cayman Chemical, Ann Arbor, MI, USA), with absorbance also measured on the VersaMax Microplate Reader. N-terminal pro-brain natriuretic peptide (NT-proBNP), an index of myocardial stress, was quantified via electrochemiluminescence immunoassay using Roche reagents on a Cobas 8000/e602 analyzer (Roche Diagnostics, Basel, Switzerland). The CV for NT-proBNP was also below 5%. The selected biochemical markers have been validated in previous studies for eval- uating cardiovascular function, inflammation, oxidative stress, and myocardial load in response to exercise. hs-CRP is a widely used marker of systemic inflammation and car- diovascular risk, responsive to acute and chronic exercise stimuli [11,21]. d-ROMs and BAP are established indicators of oxidative balance and have shown prognostic value in cardiovascular health [22,23]. NO reflects endothelial function and shear-stress-induced vasodilation [24], while SOD is a key antioxidant enzyme elevated in response to exercise- induced reactive oxygen species [25,26]. NT-proBNP is a clinically established marker of myocardial stress and is sensitive to acute hemodynamic changes during exercise [11,27]. 2.4. Statistical Analysis Statistical analysis was conducted using SPSS Statistics version 21 (IBM Corporation, Armonk, NY, USA), and all measured values were expressed as mean±standard deviation. An independentt-test was performed to compare the differences in demographic, hemody- namic, and cardiorespiratory fitness characteristics between the two groups. A two-way repeated ANOVA was used to examine the interaction effects (time×group) before and after exercise. If a significant interaction effect was found, simple main effects analyses were performed to assess between-group differences at each time point and within-group differences over time. The Pearson correlation coefficient was calculated to assess the correlation between rest blood analysis values, blood pressure, and myocardial burden ratio. Statistical significance was set atp< 0.05. 3. Results 3.1. Baseline Characteristics A total of 37 participants were included in the final analysis, with 23
were performed to assess between-group differences at each time point and within-group differences over time. The Pearson correlation coefficient was calculated to assess the correlation between rest blood analysis values, blood pressure, and myocardial burden ratio. Statistical significance was set atp< 0.05. 3. Results 3.1. Baseline Characteristics A total of 37 participants were included in the final analysis, with 23 assigned to the NBPG and 14 to the EIHG based on their SBPmax during GXT. Table mographic, hemodynamic, and cardiorespiratory fitness characteristics of the two groups. No significant differences were observed between the groups in age, height, weight, or body mass index (BMI). HRrest also did not differ significantly. However, HRmax was significantly higher in NBPG than in EIHG (p< 0.05). SBPmax and DBPmax were significantly higher in EIHG compared to NBPG (p< 0.05). There were no significant group differences in VO2max, total exercise duration, num- ber of marathons completed, weekly exercise time, training intensity, or marathon time. However, the NBPG had a significantly longer training history than the EIHG (p< 0.05). Regarding post-exercise recovery, there were no significant differences in heart rate recovery between the groups, but both systolic and diastolic blood pressure recovery (RSBP and RDBP) values were significantly higher in EIHG at all measured time points (p< 0.05).
Sports2025,13, 195 6 of 12 Table 2.Characteristics of demographic, hemodynamic, and cardiorespiratory fitness. NBPG (n= 23) EIHG (n= 14) pValue General characteristics Age, years 57.2 ±6.7 59.4 ±6.2 0.327 Height, cm 169.3 ±4.8 173.0 ±8.4 0.100 Weight, kg 65.1 ±5.6 70.3 ±11.7 0.139 BMI, m·Ht-2 23.7 ±5.0 23.3 ±1.8 0.739 Hemodynamic characteristics HRrest, BPM 56.4 ±5.5 52.3 ±9.1 0.142 HRmax, BPM 164.7 ±10.5 155.2±12.8 0.028 SBPrest, mmHg 125.7 ±9.2 127.3±11.5 0.634 SBPmax, mmHg 182.6 ±13.2 219.5±13.5 <0.001 DBPrest, mmHg 79.9 ±5.9 79.9 ±6.8 0.990 DBPmax, mmHg 93.3 ±7.6 101.6 ±5.8 0.001 HRrec (1 min), BPM 133.5 ±16.1 132.6±21.2 0.888 HRrec (2 min), BPM 112.2 ±11.2 113.8±21.2 0.761 HRrec (3 min), BPM 98.2 ±12.2 102.1±10.6 0.530 SBPR (1 min), mmHg 180.8 ±14.1 216.6±7.9 <0.001 SBPR (2 min), mmHg 173.4 ±16.0 205.7±8.8 <0.001 SBPR (3 min), mmHg 165.1 ±15.7 192.8±10.3 <0.001 DBPR (1 min), mmHg 91.8 ±7.5 100.2 ±7.6 0.003 DBPR (2 min), mmHg 87.2 ±10.3 96.0 ±6.8 0.007 DBPR (3 min), mmHg 84.4 ±10.2 92.2 ±7.2 0.019 Exercise data Training experience (years) 19.0 ±6.3 15.0 ±4.7 0.044 Marathons completed (number) 78.9 ±84.6 94.5±100.5 0.556 Exercise time (min/day) 87.4 ±35.0 72.8 ±23.0 0.191 Exercise intensity (Borg’s RPE scale) 13.1±1.8 13.1 ±1.4 0.957 Marathon time (min) 218.2 ±31.3 234.8±38.2 0.160 Physical performance VO 2max (kg/mL/min) 51.3 ±5.9 47.1 ±8.8 0.094 Total exercise (time) 808.0 ±111.1 732.1±94.3 0.041 Data are presented as mean±standard deviation. NBPG: normal blood pressure group, EIHG: exercise-induced hypertension group, BMI: body mass index, BPM: beat per minute, HR: heart rate, SBP: systolic blood pressure, DBP: diastolic blood pressure, HRrec: heat rate recovery, SBPR: systolic blood pressure recovery, DBPR: diastolic blood pressure recovery, RPE: rating of perceived exertion. 3.2. Blood Sampling and Analysis Table antioxidant capacity between the two groups. All values in parentheses indicate pre- and post-exercise measurements. Table 3.Changes in hs-CRP, d-ROMs, and BAP before and after exercise and GXT. Variable Group Pre Post pValue hs-CRP (mg/L) NBPG EIHG 0.55±0.40 0.86±0.61 0.56±0.41 0.89±0.64 0.022 a 0.076 b 0.240 c d-ROMs (U.CARR) NBPG EIHG 297.0±62.2 278.4±66.0 311.3±56.6 315.5±76.9 0.019 a 0.704 b 0.279 c BAP (µmol/L) NBPG EIHG 1840.5±268.4 1772.3±334.4
values in parentheses indicate pre- and post-exercise measurements. Table 3.Changes in hs-CRP, d-ROMs, and BAP before and after exercise and GXT. Variable Group Pre Post pValue hs-CRP (mg/L) NBPG EIHG 0.55±0.40 0.86±0.61 0.56±0.41 0.89±0.64 0.022 a 0.076 b 0.240 c d-ROMs (U.CARR) NBPG EIHG 297.0±62.2 278.4±66.0 311.3±56.6 315.5±76.9 0.019 a 0.704 b 0.279 c BAP (µmol/L) NBPG EIHG 1840.5±268.4 1772.3±334.4 2108.9±270.4 * 2097.8±330.5 * <0.001 a 0.650 b 0.567 c Data are presented as mean±standard deviation. NBPG: normal blood pressure group, EIHG: exercise-induced hypertension group, hs-CRP: high sensitive C-reactive protein, d-ROMs: derivatives of reactive oxygen metabo- lites, BAP: biological antioxidant potential, a : time, b : group, c : time×group, *: significantly different from the pre atp< 0.05.
Sports2025,13, 195 7 of 12 The inflammatory marker hs-CRP showed minimal changes in both groups: NBPG (0.55±0.40 vs. 0.56±0.41) and EIHG (0.86±0.61 vs. 0.89±0.64). The oxidative stress marker d-ROMs increased slightly in both groups—NBPG (297.0±62.2 vs. 311.3±56.6), EIHG (278.4±66.0 vs. 315.5±76.9). Antioxidant capacity, as measured by BAP, also increased post-exercise—NBPG (1840.5±268.4 vs. 2108.9±270.4), EIHG (1772.3±334.4 vs. 2097.8±330.5). However, no significant time×group interaction effects were observed for hs-CRP, d-ROMs, or BAP (p= 0.240,p= 0.279,p= 0.567, respectively). Regarding antioxidant enzyme activity and myocardial burden, significant group differences were observed. NO levels showed minimal changes—NBPG (81.7±50.9 vs. 83.4±48.3) and EIHG (124.5±74.9 vs. 119.5±69.2)—however, a significant group× time interaction was detected (p< 0.05) (FigureA). NT-proBNP, a marker of myocardial burden, increased markedly after exercise—NBPG (13.9±8.8 vs. 20.7±11.4), EIHG (23.3±13.2 vs. 36.8±24.4)—also demonstrating a significant interaction effect (p< 0.05) (FigureB). Similarly, SOD activity increased in both groups, particularly in the EIHG— NBPG (0.49±0.26 vs. 0.50±0.25), EIHG (0.69±0.50 vs. 0.83±0.61)—again with a significant group×time interaction (p< 0.05) (FigureC). Figure 2.Changes in cardiovascular biomarkers before and after exercise in the normal blood pressure group (NBPG, white bars) and the exercise-induced hypertension group (EIHG, gray bars). (A) Nitric oxide (NO,µmol/L). A significant group×time interaction was observed (p= 0.038), although within-group differences were not statistically significant. The EIHG showed a trend towards decreased NO post-exercise. #p< 0.1 vs. pre-exercise (EIHG only; trend-level significance). (B) N-terminal pro-brain natriuretic peptide (NT-proBNP, pg/mL). NT-proBNP levels significantly increased after exercise in both groups, with a higher post-exercise value in the EIHG. A significant group×time interaction was observed (p< 0.05). *p< 0.05 vs. pre-exercise; §p< 0.05 vs. NBPG (post-exercise only). (C) Superoxide dismutase (SOD, U/mL). SOD levels significantly increased only in the EIHG post-exercise. A significant group×time interaction was found (p< 0.05). *p< 0.05 vs. pre-exercise (EIHG only).
Description
The study examines cardiovascular responses in runners with exercise-induced hypertension.