This study aims to compare the effects of aerobic exercise (AE) and physiological ischemic training (PIT) on inflammatory and angiogenesis biomarkers (VEGF, IL-6, IL-10), cardiorespiratory fitness, muscle strength, and quality of life in patients with grade 2 primary hypertension (HT2). This randomized controlled trial will involve 60 HT2 patients from Pratama and Utama Medika Antapani Clinic, who will be assigned to either AE or PIT groups. The intervention will last 6 weeks, and outcomes measured will include biomarker levels, VO2max, 6-minute walk distance (6-MWD), maximum voluntary contraction (MVC), and SF-36 questionnaire scores.

Background: Grade 2 primary hypertension (HT2) can negatively affect cardiovascular health and quality of life. Physical exercise is a non-pharmacological intervention that may modulate inflammatory and angiogenesis biomarkers, as well as improve fitness and patient-reported outcomes. This study aims to compare the effects of aerobic exercise (AE) and physiological ischemic training (PIT) on HT2 patients.

Methods: This randomized controlled trial will include 60 HT2 patients from Pratama and Utama Medika Antapani Clinic. Participants will be randomly assigned to AE or PIT groups. The intervention will last 6 weeks. Outcomes to be measured include vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-10 (IL-10), cardiorespiratory fitness (VO2max, 6-minute walk distance [6-MWD]), muscle strength (maximum voluntary contraction [MVC]), and quality of life (SF-36 questionnaire).

Inclusion Criteria:

1. Primary hypertension patients aged 18-65 years
2. Diagnosed with grade 2 primary hypertension
3. Willing to participate in the study

Exclusion Criteria:

1. Patients with unstable angina
2. Malignant arrhythmias and high atrioventricular block
3. Unstable hemodynamics
4. Uncontrolled hypertension
5. Acute pericarditis
6. Severe valvular heart disease
7. Chronic obstructive pulmonary disease
8. Cor pulmonale and pulmonary vascular disease
9. Thrombophlebitis
10. Intermittent claudication
11. Cognitive impairment
12. Uncooperative subjects
13. Subjects experiencing infection or inflammation
14. Subjects with neuromuscular disorders that may affect the study results
15. Subjects with musculoskeletal disorders that may affect the study results
16. Complications or comorbidities such as cerebrovascular disease, CAD, atheroma plaques on imaging, heart failure, PAD, and atrial fibrillation.

Individual participant data, after de-identification, will be made available to qualified researchers upon request. Requests will be reviewed by the study team and shared under data use agreements to ensure participant privacy and compliance with ethical guidelines.