Hypertension and retinal microvascular dysfunction (HyperVasc): protocol of a randomised controlled exercise trial in patients with hypertension

Abstract

IntroductionHypertension is a global healthcare burden that affects the structure and function of the macrocirculation and microcirculation and induces disease-specific end-organ damage. Vascular biomarkers are essential to timely diagnose this end-organ damage to improve cardiovascular (CV) risk stratification and medical decision making. Exercise therapy is an effective means to improve vascular health and reduce overall CV risk. However, it is still not clear whether high-intensity interval training (HIIT) is recommendable for patients with hypertension to reduce blood pressure, increase cardiorespiratory fitness and ameliorate vascular health.Methods and analysisThe ‘Hypertension and retinal microvascular dysfunction’ trial will investigate macrovascular and microvascular impairments in hypertensive patients compared with healthy controls to investigate hypertension-induced end-organ damage by using gold-standard methods as well as newly developed unique retinal microvascular biomarkers. In addition, this trial will investigate the reversibility of retinal end-organ damage by assessing the effects of an 8-week supervised and walking based HIIT on blood pressure, cardiorespiratory fitness as well as macrovascular and microvascular health, compared with a control group following standard physical activity recommendations. Primary outcome will be the arteriolar-to-venular diameter ratio. Secondary outcomes will be arteriolar and venular diameters as well as the flicker-light-induced dilation. Further outcomes will be other retinal microvascular biomarkers, flow-mediated dilation of the brachial artery as well as blood pressure, cardiorespiratory fitness, microalbuminuria, hypertensive retinopathy and classical CV risk markers. Analysis of variance and analysis of covariance will be used to investigate group differences between healthy controls and hypertensive patients and training effects in hypertensive patients, respectively.Ethics and disseminationThe Ethics Committee of Northwestern and Central Switzerland approved this study (EKNZ-2021-00086). All participants will give informed consent.Trial registration numberNCT04763005.

Short‐term high‐intensity interval training improves micro‐ but not macrovascular function in hypertensive patients

“…We recently published the study protocol of the “Hypertension and retinal microvascular dysfunction” (HyperVasc) study with an extensive description of all study procedures 35 . The present study is part of the Hypervasc trial and included 41 patients with hypertension.…”

“…All vascular assessments were performed by one experienced investigator. Extensive description of vascular assessments can be found in the study protocol 35 …”

“…Venous blood samples were taken and stored at −80°C until further analyses after the data acquisition was completed. Physical fitness was analyzed by an individualized bicycle ramp protocol as described previously 35,41 . Peak oxygen uptake (V̇O 2 peak) and maximal heart rate (HRmax) were analyzed using the Cortex Metalyzer R 3B metabolic test system (Cortex Biophysik GmbH).…”

“…Extensive description of vascular assessments can be found in the study protocol. 35 Briefly, FMD was assessed, measuring the brachial artery using a semiautomatic, ECG-guided high-resolution B-mode ultrasound system (UNEX EF 38G, UNEX Corp.) and a BP cuff, which was applied to the forearm of the patient. After a short period of rest, the blood pressure cuff was inflated and cuff pressure increased 50 mmHg above resting systolic blood pressure for 5 min.…”

“…Physical fitness was analyzed by an individualized bicycle ramp protocol as described previously. 35,41 Peak oxygen uptake (VȮ 2 peak) and maximal heart rate (HRmax) were analyzed using the Cortex Metalyzer R 3B metabolic test system (Cortex Biophysik GmbH). Exhaustion was achieved when the predefined respiratory exchange ratio (RER) for the respective age group was reached (40-59 years RER ≥ 1.10; 60-69 years RER ≥ 1.06).…”