Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation.

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.

Background The primary objective of this study is twofold: (1) to examine the effect of COVID-19 safety measures, enacted to prevent transmission of SARS-nCOV-2, on total physical activity in the adult general population (≥ 18 years) and (2) to analyze the impact of the factor “severity of safety measures” on potential changes in physical activity. The secondary objective is to investigate the effects of safety measures on the respective PA intensities, i.e., sedentary behavior, light, moderate, and vigorous physical activity. Methods A systematic literature search will be performed in the following online databases: Medline (on Ovid), Web of Science, Scopus, L.OVE Coronavirus disease by Epistemonikos, and ProQuest Dissertations & Theses A&I. All obtained citations will undergo title and abstract as well as full-text screening by two independent reviewers. Observational studies investigating the effects of safety measures on physical activity patterns in the adult general population will be included. The standardized mean difference in total physical activity per time unit between pre- and during COVID-19 or between normative data and during COVID-19 will be the primary outcome. The standardized mean difference in sedentary time, light, moderate, and vigorous physical activity will be assessed as secondary outcomes. Eligible studies will be divided between the reviewers for data extraction using a pilot-tested data form. Risk of bias assessment will be performed using a standard assessment tool. If suitable, a random-effects meta-analysis and meta-regression with a unit of safety measure severity as the independent variable will be performed. Discussion This study will synthesize available data reporting the effect of COVID-19 safety measures on physical activity patterns in adults. Furthermore, we will incorporate a unit for the severity of safety measures for better generalizability of the results. These findings will be of great value for public health policymaking and estimating future health consequences. Systematic review registration PROSPERO CRD42021231039.

This study was registered on Clini calTr ials.gov (NCT04763005).