Sex-specific and polygenic effects underlying resting heart rate and associated risk of cardiovascular disease.

Aims: Resting heart rate (RHR) is associated with cardiovascular disease (CVD) and mortality. This study aimed to identify genetic loci associated with RHR, develop a genome-wide polygenic risk score (PRS) for RHR, and assess associations between the RHR PRS and CVD outcomes, to better understand the biological mechanisms linking RHR to disease. Sex-specific analyses were conducted to potentially elucidate different pathways between the sexes.

Insight into the relationship between resting heart rate and atrial fibrillation: a Mendelian randomization study.

Aims: A low resting heart rate (RHR) implies a more efficient heart function and a lower risk of cardiovascular disease. However, observational studies have reported a U-shaped association between RHR and atrial fibrillation (AF). In contrast, Mendelian randomization (MR) studies have found an inverse causal association between RHR and AF.

Associations of polygenic inheritance of physical activity with aerobic fitness, cardiometabolic risk factors and diseases: the HUNT study.

Physical activity (PA), aerobic fitness, and cardiometabolic diseases (CMD) are highly heritable multifactorial phenotypes. Shared genetic factors may underlie the associations between higher levels of PA and better aerobic fitness and a lower risk for CMDs. We aimed to study how PA genotype associates with self-reported PA, aerobic fitness, cardiometabolic risk factors and diseases.

Exploring shared genetics between maximal oxygen uptake and disease: the HUNT study.

Low cardiorespiratory fitness, measured as maximal oxygen uptake (V̇o), is associated with all-cause mortality and disease-specific morbidity and mortality and is estimated to have a large genetic component (∼60%). However, the underlying mechanisms explaining the associations are not known, and no association study has assessed shared genetics between directly measured V̇o and disease. We believe that identifying the mechanisms explaining how low V̇o is related to increased disease risk can contribute to prevention and therapy.

The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy.

Background: Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment.

Purpose: We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention.

Associations between circulating microRNAs and lipid-rich coronary plaques measured with near-infrared spectroscopy.

Lipid-rich coronary atherosclerotic plaques often cause myocardial infarction (MI), and circulating biomarkers that reflect lipid content may predict risk of MI. We investigated the association between circulating microRNAs (miRs) are lipid-rich coronary plaques in 47 statin-treated patients (44 males) with stable coronary artery disease undergoing percutaneous coronary intervention. We assessed lipid content in non-culprit coronary artery lesions with near-infrared spectroscopy and selected the 4 mm segment with the highest measured lipid core burden index (maxLCBI).

Lipoprotein subfraction profiling in the search of new risk markers for myocardial infarction: The HUNT study.

Background: Traditional biomarkers used to measure risk of myocardial infarction (MI) only explain a modest proportion of the incidence. Lipoprotein subfractions have the potential to improve risk prediction of MI.

Aim: We aimed to identify lipoprotein subfractions that were associated with imminent MI risk.

Small LDL subfractions are associated with coronary atherosclerosis despite no differences in conventional lipids.

Lipoprotein subfractions currently represent a new source of cardiovascular disease (CVD) risk markers that may provide more information than conventional lipid measures. We aimed to investigate whether lipoprotein subfractions are associated with coronary atherosclerosis in patients without prior known CVD. Fasting serum samples from 60 patients with suspected coronary artery disease (CAD) were collected before coronary angiography and analyzed by nuclear magnetic resonance (NMR) spectroscopy.

COX7A2L genetic variants determine cardiorespiratory fitness in mice and human.

Mitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans.

Genome-Wide Association Study Identifies New Genetic Determinants of Cardiorespiratory Fitness: The Trøndelag Health Study.

Purpose: Low cardiorespiratory fitness (CRF) is a major risk factor for cardiovascular disease (CVD) and a stronger predictor of CVD morbidity and mortality than established risk factors. The genetic component of CRF, quantified as peak oxygen uptake (V̇O 2peak ), is estimated to be ~60%. Unfortunately, current studies on genetic markers for CRF have been limited by small sample sizes and using estimated CRF.

Associations between circulating microRNAs and coronary plaque characteristics: potential impact from physical exercise.

microRNAs (miRs) are involved in different steps in the development of atherosclerosis and are proposed as promising biomarkers of coronary artery disease (CAD). We hypothesized that circulating levels of miRs were associated with coronary plaque components assessed by radiofrequency intravascular ultrasound (RF-IVUS) before and after aerobic exercise intervention. Thirty-one patients with CAD treated with percutaneous coronary intervention (PCI) previously included in a randomized trial with aerobic interval training (AIT) or moderate continuous training (MCT) as post-PCI intervention were included.

Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study.

Background And Aims: Low cardiorespiratory fitness is a strong and independent risk factor for cardiovascular disease (CVD). Serum profiling of healthy individuals with large differences in cardiorespiratory fitness may therefore reveal early biomarkers of CVD development. Thus, we aimed to identify circulating lipoprotein subfractions differentially expressed between groups of individuals with large differences in cardiorespiratory fitness, measured as maximal oxygen uptake (VO).

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

Background: Low cardiorespiratory fitness (V̇O) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O, there is considerable inter-individual variability in the V̇O response to the same dose of exercise. Understanding how genetic factors contribute to V̇O training response may improve personalisation of exercise programs.

Circulating MicroRNA-210 Concentrations in Patients with Acute Heart Failure: Data from the Akershus Cardiac Examination 2 Study.

Background: MicroRNA (miR)-210 expression is induced by acute and chronic hypoxia and provides prognostic information in patients with aortic stenosis and acute coronary syndrome. We hypothesized that circulating miR-210 concentrations could provide diagnostic and prognostic information in patients with acute heart failure (HF).

Methods: We measured miR-210 concentrations in serum samples on admission from 314 patients hospitalized for acute dyspnea and 9 healthy control subjects.

Identification of novel genetic variants associated with cardiorespiratory fitness.

Introduction: Low maximal oxygen uptake (VO) is a strong and independent risk factor for all-cause and cardiovascular disease (CVD) mortality. For other CVD risk factors, numerous genetic association studies have been performed, revealing promising risk markers and new therapeutic targets. However, large genomic association studies on VO are still lacking, despite the fact that VO has a large genetic component.

Circulating microRNAs as predictive biomarkers of myocardial infarction: Evidence from the HUNT study.

Background And Aims: Several risk prediction models for coronary heart disease (CHD) are available today, however, they only explain a modest proportion of the incidence. Circulating microRNAs (miRs) have recently been associated with processes in CHD development, and may therefore represent new potential risk markers. The aim of the study was to assess the incremental value of adding circulating miRs to the Framingham Risk Score (FRS).

A Multi-Center Comparison of O Trainability Between Interval Training and Moderate Intensity Continuous Training.

There is heterogeneity in the observed O response to similar exercise training, and different exercise approaches produce variable degrees of exercise response (trainability). The aim of this study was to combine data from different laboratories to compare O trainability between various volumes of interval training and Moderate Intensity Continuous Training (MICT). For interval training, volumes were classified by the duration of total interval time.

Effect of high-intensity interval training on cardiovascular disease risk factors and body composition in psoriatic arthritis: a randomised controlled trial.

Background: Psoriatic arthritis (PsA) is associated with an accumulation of cardiovascular disease (CVD) risk factors. The aim of this study was to evaluate the effect of high-intensity interval training (HIIT) on CVD risk factors in patients with PsA.

Methods: We randomly assigned 61 patients with PsA (41 women and 20 men) to an intervention group performing HIIT for 11 weeks or a control group who were instructed to not change their physical exercise habits.

Powerful extreme phenotype sampling designs and score tests for genetic association studies.

We consider cross-sectional genetic association studies (common and rare variants) where non-genetic information is available or feasible to obtain for N individuals, but where it is infeasible to genotype all N individuals. We consider continuously measurable Gaussian traits (phenotypes). Genotyping n < N extreme phenotype individuals can yield better power to detect phenotype-genotype associations, as compared to randomly selecting n individuals.

Impact of High-Intensity Interval Training on Disease Activity and Disease in Patients With Psoriatic Arthritis: A Randomized Controlled Trial.

Objective: To evaluate the impact of high-intensity interval training (HIIT) on disease activity and disease perception in patients with psoriatic arthritis (PsA) and to evaluate whether a potential effect could be sustained for a longer period of time.

Methods: We randomly assigned 67 patients with PsA (43 women and 24 men) to an intervention group in which patients performed HIIT for 11 weeks or a control group of patients who were instructed not to change their physical exercise habits. Outcomes were assessed at 3 months and 9 months with the patient's global assessment (PGA), fatigue, and pain scores measured on a 100-mm visual analog scale (VAS), and the composite Disease Activity Score in 44 joints (DAS44) was calculated.

MicroRNAs as Important Regulators of Exercise Adaptation.

A significant body of evidence supports the protective role of exercise training (ET) in cardiovascular diseases, skeletal muscle dystrophies, several types of cancer, Alzheimer disease or even in the recovery of spinal cord injury. In spite of this, the molecular mechanisms underlying the beneficial effects of exercise training are not well understood and remain elusive. Several mechanisms have been proposed in the past, but more recently microRNAs (miRNAs), small non-coding RNA molecules involved in a variety of basic biological processes that negatively modulate gene expression, recognized as important regulatory molecules.

Circulating microRNAs predict future fatal myocardial infarction in healthy individuals - The HUNT study.

Coronary heart disease is the most common cause of death, and the number of individuals at risk is increasing. To better manage this pandemic, improved tool for risk prediction, including more accurate biomarkers are needed. The objective of this study was to assess the utility of circulating microRNAs (miRs) to predict future fatal acute myocardial infarction (AMI) in healthy participants.

The effects of high intensity interval training in women with rheumatic disease: a pilot study.

Purpose: Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are inflammatory diseases which involve increased risk of cardiovascular disease (CVD). High intensity interval training (HIIT) is known to be effective in improving cardiovascular health. The aim of this study was to investigate whether 10 weeks of HIIT at 85-95% of HRmax would improve important risk factors of CVD in rheumatic patients, and if these patients would tolerate exercise intensities above today's recommendations.

A small molecule activator of AKT does not reduce ischemic injury of the rat heart.

Background: Activation of protein kinase AKT is required for cardioprotection by ischemic preconditioning, and transgenic overexpression of AKT protects the heart against ischemia. However, it is unknown whether acute pharmacological activation of AKT alone, using a therapeutically relevant strategy, induces cardioprotection. In this study we provide the first evidence to clarify this question.