Exercise-induced effects on coronary atherosclerosis assessed by grayscale and radiofrequency intravascular ultrasound

Coronary atherosclerosis is a leading cause of morbidity and mortality worldwide. Physical inactivity is an independent risk factor for coronary artery disease, and physically active patients have an improved prognosis compared to sedate patients. Although the clinical relationship between exercise and cardiovascular health is convincing, the pathophysiological mechanisms responsible for improved outcomes in this large patient group are largely unknown. In a randomized controlled trial, we assessed exercise-induced effects on coronary atherosclerosis in 36 patients with established coronary artery disease undergoing stent implantation and optimal medical therapy. Patients exercised for 12 weeks, either following an aerobic interval training protocol, or performing moderate continuous exercise. Coronary atherosclerosis was assessed by grayscale and radiofrequency intravascular ultrasound, quantifying both plaque geometry and tissue characteristics. Our main findings were that with both exercise protocols there was a significant reduction in necrotic core (≈ 3 %) and a strong trend towards a reduction of plaque burden (≈ 10 %) in non-stented coronary segments and in separate atheroma lesions. There were no differences between exercise groups. In a post-hoc analysis of data from the randomized controlled trial, we assessed clinical factors at baseline that potentially were associated with a reduction in necrotic core and plaque burden at follow-up. We found a strong association between the clinical presentation of disease and necrotic core volume reduction after aerobic exercise (p=0.011). The association was in favor of patients with stable coronary artery disease, and necrotic core volume reduction was much more frequent in these patients (17/18) than in patients with unstable coronary artery disease (8/18). There were no significant associations between any clinical baseline explanatory variables and plaque burden reduction at follow-up. In a third study conducted within a subgroup of patients included in the randomized controlled trial, we assessed the reproducibility of intravascular ultrasound data acquisition in stented coronary arteries. This was performed by repeating the intravascular ultrasound pullback twice at the same time-point, thus simulating data collection in a serial imaging study. Our main finding was that the inter-pullback reproducibility of geometrical data was very good for non-stented segments with relative differences between pullbacks < 5 %. For stented segments reproducibility was poorer, though acceptable, and < 10 %. Taken together, the data presented in this thesis strengthens the scientific evidence for beneficial exercise-induced effects on coronary atherosclerosis, not only with respect to atherosclerotic burden, but also with respect to plaque vulnerability. Furthermore, exerciseinduced effects on coronary atherosclerosis may be more beneficial in patients with stable coronary artery disease compared to patients in the early phase after an acute coronary syndrome. Finally, serial intravascular ultrasound imaging in stented coronary arteries seems to be associated with a variability of 5–10 % attributed to the acquisition of images itself, which may have implications for the design of future serial stent studies

Peak oxygen uptake after cardiac rehabilitation: a randomized controlled trial of a 12-month maintenance program versus usual care.

Exercise capacity is a strong predictor of survival in patients with coronary artery disease (CAD). Exercise capacity improves after cardiac rehabilitation exercise training, but previous studies have demonstrated a decline in peak oxygen uptake after ending a formal rehabilitation program. There is a lack of knowledge on how long-term exercise adherence can be achieved in CAD patients. We therefore assessed if a 12-month maintenance program following cardiac rehabilitation would lead to increased adherence to exercise and increased exercise capacity compared to usual care.Two-centre, open, parallel randomized controlled trial with 12 months follow-up comparing usual care to a maintenance program. The maintenance program consisted of one monthly supervised high intensity interval training session, a written exercise program and exercise diary, and a maximum exercise test every third month during follow-up. Forty-nine patients (15 women) on optimal medical treatment were included following discharge from cardiac rehabilitation. The primary endpoint was change in peak oxygen uptake at follow-up; secondary endpoints were physical activity level, quality of life and blood markers of cardiovascular risk.There was no change in peak oxygen uptake from baseline to follow-up in either group (intervention group 27.9 (±4.7) to 28.8 (±5.6) mL·kg (-1) min (-1), control group 32.0 (±6.2) to 32.8 (±5.8) mL·kg (-1) min (-1), with no between-group difference, p = 0.22). Quality of life and blood biomarkers remained essentially unchanged, and both self-reported and measured physical activity levels were similar between groups after 12 months.A maintenance exercise program for 12 months did not improve adherence to exercise or peak oxygen uptake in CAD patients after discharge from cardiac rehabilitation compared to usual care. This suggests that infrequent supervised high intensity interval training sessions are inadequate to improve peak oxygen uptake in this patient group.ClinicalTrials.gov NCT01246570

Inflammation is strongly associated With cardiorespiratory fitness, sex, BMI, and the metabolic syndrome in a self-reported healthy population: HUNT3 Fitness Study

Objective: To investigate whether C-reactive protein (CRP, a general marker of inflammation), neopterin (activated macrophages), lactoferrin (activated neutrophils), and endothelial function (flow-mediated vasodilation [FMD]) are associated with cardiorespiratory fitness (peak oxygen uptake [VO ]), sex, body mass index (BMI), and the metabolic syndrome (MetSyn) in a healthy adult population. Patients and Methods: This was a cross-sectional association study based on the population-based HUNT3 Fitness Study performed from May 15, 2007, through June 23, 2008. Seven hundred forty self-reported healthy respondents (327 women) identified as having the MetSyn were age- and sex-matched with 692 controls (307 women) from the same cohort. Associations between the inflammatory biomarkers and VO , FMD, and the MetSyn were analyzed by multivariate linear regression. Results: The CRP level was negatively associated with VO (

Cardiovascular risk factors have larger impact on endothelial function in self-reported healthy women than men in the HUNT3 Fitness study.

BACKGROUND: Several studies suggest that cardiovascular risk factors comprising the metabolic syndrome have larger effects on the development of cardiovascular disease in women than in men. A recent study in self-reported healthy subjects demonstrated a marked gender difference in endothelial dysfunction that may be an important precursor of manifest cardiovascular disease. The aim of the present study was to determine whether the association between endothelial function and cardiovascular risk factors is different in self-reported healthy women compared to self-reported healthy men. METHODS AND RESULTS: Associations between endothelial function (flow mediated dilation, FMD, of the brachial artery measured by ultrasound), anthropometric variables, peak oxygen uptake (VO2peak), blood pressure, serum lipids, blood glucose and a questionnaire on general health and lifestyle including smoking status were studied by logistic and linear regression in 2 528 women and 2 211 men aged 20-89 years, free from self-reported cardiovascular disease. In women with hyperglycemia, endothelial dysfunction (FMD ≤0%) occurred twice as frequently as in male counterparts. The presence of the metabolic syndrome, high blood pressure and low VO2peak increased the prevalence of endothelial dysfunction more in women than in men. CONCLUSION: Endothelial dysfunction is more strongly associated with cardiovascular risk factors in self-reported healthy women than in self-reported healthy men. This finding could explain why the metabolic syndrome, and especially hyperglycemia, is associated with higher cardiovascular risk and a worse prognosis in women

Patient characteristics and medication use at baseline.

<p>Data are given as numbers with percentages in parenthesis when not otherwise specified. PCI; percutaneous coronary intervention, CABG; coronary artery bypass grafting, PAD; peripheral artery disease, ACE; angiotensin converting enzyme inhibitors, ARA; angiotensin II receptor antagonists. * Between group difference at baseline (p = 0.02).</p><p>Patient characteristics and medication use at baseline.</p

Perioperative factors associated with changes in troponin T during coronary artery bypass grafting

Objective Investigate important clinical and operative variables associated with increases in cardiac troponin T (cTnT) as indicators of myocardial injury after coronary artery bypass grafting (CABG). Design Prospective cohort study. Setting Single university hospital. Participants The study comprised 626 patients undergoing isolated CABG from April 2008 through April 2010 with a validation cohort (n = 686) from 2015-2017. Interventions None. Measurements and Main Results Perioperative variables were registered prospectively. The extent of diffuse coronary atherosclerosis and significant stenoses were assessed with preoperative coronary angiography. Mixed model analysis was used to construct a statistical model explaining the course of cTnT concentrations. The model was adjusted for preoperative and intraoperative/postoperative myocardial infarction (MI) for independent assessment of additional variables. Clinical factors associated with increased cTnT concentrations during and after CABG were longer duration of cardiopulmonary bypass (p < 0.001), higher preoperative creatinine (p < 0.001), New York Heart Association functional classification IV (p = 0.006), reduced LVEF (p = 0.034), higher preoperative C-reactive protein (p = 0.049), and intraoperative/postoperative MI (p < 0.001). Factors associated with decreasing cTnT concentrations during CABG were higher BSA (p < 0.001) and a recent preoperative MI (p < 0.001). The extent of diffuse coronary atherosclerosis and significant stenoses were not associated with changes in cTnT (p = 0.35). Results were similar in the validation cohort. Conclusions Left ventricular ejection fraction, New York Heart Association classification, kidney function, inflammation status, duration of cardiopulmonary bypass, body surface area, and preoperative MI were associated with the cTnT rise-and-fall pattern related to myocardial injury after CABG. Information regarding these variables may be valuable when using cTnT in the diagnostic workup of postoperative MI

Flow chart of participants throughout the study.

<p>Flow chart of participants throughout the study.</p

Outcome measures at baseline and after 12 months follow-up.

<p>VO_2peak; peak oxygen uptake, RER_peak; respiratory exchange ratio at peak oxygen uptake, HR_peak; peak heart rate, HRR, 1 min; heart rate recovery the first minute after ending an exercise test, HR; resting heart rate, SBP; systolic blood pressure, DBP; diastolic blood pressure, BMI; body mass index, hsCRP; high-sensitive C-reactive protein, LDLc; low-density lipoprotein cholesterol, HDLc; high-density lipoprotein cholesterol, TG; triglycerides, HbA1c; glycosylated haemoglobin.</p><p>* indicates within-group changes from baseline to 12 months,</p>‡<p> indicates between groups changes in mean difference.</p><p>Outcome measures at baseline and after 12 months follow-up.</p

Self-reported physical activity.

<p>Data are given as numbers with percentages in parenthesis.</p><p>* Valid questionnaires for 19 patients at baseline and 21 patients at follow-up in the intervention group, and 22 patients at baseline and follow-up in the control group.</p><p>Self-reported physical activity.</p

Flow-mediated dilation with number of risk factors present.

<p>Mean flow mediated dilation adjusted for age and its dependence on risk factors included in the definition of the metabolic syndrome (waist obesity, hypertension, hyperglycemia, low HDL, and high trigycerides) are shown separately for women and men. Vertical lines indicate 95% confidence intervals.</p