Abstract

BACKGROUND There is mounting evidence that exercise hypertension (EH) in hypertensive patients is linked to cardiovascular disease events, end-organ damage, and mortality. Nevertheless, standardized treatment options for reducing EH in these patients have yet to be established. Our study provides robust clinical evidence regarding the selection of antihypertensive medications for hypertensive patients with EH. Concurrently, we assessed the impact of specific antihypertensive drugs on cardiorespiratory exercise performance in hypertensive patients.

METHODS Clinical data from 205 patients with essential hypertension who achieved standard resting blood pressure after 3 months of medication were retrospectively collected from the Cardiology Department of Xi’an Jiaotong University Second Affiliated Hospital and the Cardiology Department of Xi’an Jiaotong University First Affiliated Hospital between April 2023 and April 2024. Baseline characteristics, hypertension treatment options, and cardiopulmonary exercise test (CPET) indicators were recorded. hypertension treatment options included monotherapy with β-blockers(BBs), angiotensin receptor neprilysin inhibitors (ARNI), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), or calcium channel blockers(CCB); as well as combination therapy without BBs or ARNI, ARNI combined with non-BBs, BBs combined with non-ARNI, and BBs + ARNI combined with other drugs. Patients were categorized into EH group and general group based on their CPET results. Logistic regression analysis was used to assess the correlation between diverse monotherapy or combination treatment options and EH. Additionally, based on specific drug usage, patients were divided into four groups for further analysis: β-blocker group (with BBs but no ARNI), ARNI group (with ARNI but no BBs), β-blocker + ARNI combined group (with both BBs and ARNI), and other drug group (without BBs or ARNIs). Multiple sample rank sum tests along with multiple comparison analyses were conducted to evaluate the effects of specific drugs on heart rate response (HRr), blood pressure response (BPr), peak oxygen uptake (VO2peak), ΔVO2/ΔW, VE/VCO2 slope, peak minute ventilation (VEpeak), anaerobic threshold (AT), and heart rate recovery at 1 minute post-exercise(HRR at lmin).

RESULTS In monotherapy options, BBs significantly reduced the risk of EH across all three models constructed (OR=0.072, 95% CI:0.012-0.43, p=0.004); For combination therapy options, BBs combined with non-ARNI also showed a significant reduction in EH risk across all three models constructed (OR=0.172, 95% CI:0.052-0.572, p=0.004) ; while BBs + ARNI combined with other drugs demonstrated a decreased the risk of EH in model 1 and model 2 (OR=0.145, 95% CI:0.041-0.508, p=0.003) and (OR=0.15, 95% CI:0.039-0.574, p=0.006) . Among the specific drug group, BBs were found to be more effective than other drugs in reducing HPr (14.60 vs. 17.60 bpm/met, p=0.002), BPr (12.70 vs.14.40 mmHg/met, p=0.014), VO2peak (16.80 vs. 18.80 ml/kg/min, p=0.023), HRR at 1min≤12 times/minute proportion ( 12.7% vs. 34.1%, p=0.003 ) , and than ARNI in reducing BPr (12.70 vs. 14.60 mmHg/met, p=0.035)and VO2peak(16.80 vs. 18.80 ml/kg/min, p=0.006) .Furthermore, BBs + ARNI were found to be more effective than other drugs in reducing HRr(14.25 vs. 17.60 bpm/met, p=0.031), VO2peak(16.30 VS 18.80 ml/kg/min, p=0.008), and than ARNI in reducing VO2peak(16.30 VS 19.30 ml/kg/min, p=0.002).

CONCLUSIONS Among essential hypertensive patients achieving standard resting blood pressure levels through antihypertensive therapy, monotherapy or combination therapy involving BBs can reduce the risk of EH. However, ACEI/ARBs, ARNI or CCBs alone did not demonstrate a reduction in EH risk. Compared to ARNI alone or combined use thereof, monotherapy or combination therapy involving BBs reduces cardiorespiratory tolerance, slows down heart rate and blood pressure responses during exercise, and increases vagal tone following physical activity in hypertensive patients.

What Is New?We elucidated the effects of diverse hypertension treatment options on EH risk in essential hypertensive patients, as well as the influence of specific antihypertensive medications on cardiopulmonary exercise performance in this population.

What Is Relevant Essential hypertension (EH) primarily involves sympathetic nervous system(SNS) activation. β-blockers(BBs) inhibit cardiac SNS activation, thereby reducing EH incidence. Although BBs negatively impact exercise tolerance during exercises, they increase post-exercise vagal nerve tone.

Clinical/Pathophysiological Implications?This study offers valuable insights into antihypertensive treatment options for essential hypertensive patients with EH.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the Key Research and Development Program of Shaanxi Province grant 2020ZDLSF02-09

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study received approval from the Medical Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (approval number: 2020055).

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Nonstandard Abbreviations and AcronymsEHExercise hypertensionCPETCardiopulmonary exercise testSBPSystolic blood pressureBBsβ-blockersARNIAngiotensin receptor neprilysin inhibitorsCCBCalcium channel blockersBPrBlood pressure responseVO2peakPeak oxygen uptakeRERRespiratory exchange rateΔVO2/ΔWRatio of oxygen uptake change to power changeVE/VCO2slope Carbon dioxide ventilation equivalent slopeVEpeakPeak minute ventilationATAnaerobic thresholdHRR at lminHeart rate recovery at 1 minute post-exerciseSNSSympathetic nervous systemHRrHeart rate responseNPsNatriuretic peptide systemRAASRenin-angiotensin-aldosterone systemMETMetabolic equivalent