Erik Madssen

The higher the better? Interval training intensity in coronary heart disease

OBJECTIVES Peak oxygen uptake (VO2 peak) increases more after high intensity interval training compared to isocaloric moderate exercise in patients with coronary heart disease (CHD). We assessed the impact of exercise intensity during high intensity intervals on the increase in VO2 peak. DESIGN/METHODS We included 112 patients with coronary heart disease who had participated in randomized trials of interval training consisting of four times four minutes intervals at 85-95% of heart rate maximum (HRmax) for 12 weeks. Exercise intensity was calculated for each patient using HR during the two last minutes of each interval, expressed as percentage of HRmax. We used a univariate general linear model with VO2 peak increase as the dependent variable and percentage of HRmax, age, number of exercise sessions, and baseline VO2 peak as covariates. Exercise intensity was also divided into three categories; <88%, 88-92%, and >92% of HRmax, and these categories were used as a fixed factor in the model. RESULTS VO2 peak increased by 3.9 (SD 3.1) mL kg(-1)min(-1), equal to 11.9% after 23.4 exercise sessions. Percentage of HRmax had a significant effect on increase in VO2 peak, both as a continuous (p=0.019) and categorical variable (p=0.020). The estimated marginal means and 95% confidence intervals of the increase in VO2 peak for the three intensity categories were 3.1 (2.0, 4.2), 3.6 (2.8, 4.4), and 5.2 (4.1, 6.3) for the <88%, the 88-92%, and the >92% category, respectively. CONCLUSIONS Even within the high intensity training zone, exercise intensity was an important determinant for improving VO2 peak in patients with coronary heart disease.

Insomnia and Endothelial Function – The HUNT 3 Fitness Study

Background Insomnia is associated with increased risk of coronary heart disease (CHD), but the underlying mechanisms are not understood. To our knowledge, no previous studies have examined insomnia in relation to endothelial function, an indicator of preclinical atherosclerosis. Our aim was to assess the association of insomnia with endothelial function in a large population based study of healthy individuals. Methods A total of 4 739 participants free from known cardiovascular or pulmonary diseases, cancer, and sarcoidosis, and who were not using antihypertensive medication were included in the study. They reported how often they had experienced difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Endothelial function was measured by flow mediated dilation (FMD) derived from the brachial artery. Results We found no consistent association between the insomnia symptoms and endothelial function in multiadjusted models, but individual insomnia symptoms may be related to endothelial function. Among women who reported early awakenings, endothelial function may be lower than in women without this symptom (p = 0.03). Conclusions This study provided no evidence that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD. Further studies are needed to explore the complex interrelation between sleep and cardiovascular pathology.

Coronary Atheroma Regression and Plaque Characteristics Assessed by Grayscale and Radiofrequency Intravascular Ultrasound After Aerobic Exercise

The aim of the present study was to investigate effects of aerobic interval training (AIT) versus moderate continuous training (MCT) on coronary atherosclerosis in patients with significant coronary artery disease on optimal medical treatment. Thirty-six patients were randomized to AIT (intervals at ≈ 90% of peak heart rate) or MCT (continuous exercise at ≈ 70% of peak heart rate) 3 times a week for 12 weeks after intracoronary stent implantation. Grayscale and radiofrequency intravascular ultrasounds (IVUS) were performed at baseline and follow-up. The primary end point was the change in plaque burden, and the secondary end points were change in necrotic core and plaque vulnerability. Separate lesions were classified using radiofrequency IVUS criteria. We demonstrated that necrotic core was reduced in both groups in defined coronary segments (AIT -3.2%, MCT -2.7%, p <0.05) and in separate lesions (median change -2.3% and -0.15 mm(3), p <0.05). Plaque burden was reduced by 10.7% in separate lesions independent of intervention group (p = 0.06). No significant differences in IVUS parameters were found between exercise groups. A minority of separate lesions were transformed in terms of plaque vulnerability during follow-up with large individual differences between and within patients. In conclusion, changes in coronary artery plaque structure or morphology did not differ between patients who underwent AIT or MCT. The combination of regular aerobic exercise and optimal medical treatment for 12 weeks induced a moderate regression of necrotic core and plaque burden in IVUS-defined coronary lesions.

Peak Oxygen Uptake after Cardiac Rehabilitation: A Randomized Controlled Trial of a 12-Month Maintenance Program versus Usual Care

Background 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. Materials and Methods 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. Results 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. Conclusions 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. Trial Registration ClinicalTrials.gov NCT01246570

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.

Risk of acute myocardial infarction: dyslipidemia more detrimental for men than women.

Background: Endogenous estrogens prevent lipid peroxidation, which is pivotal in atherogenesis. Dyslipidemia may therefore be more dangerous for men than for women as a risk factor for acute myocardial infarction (AMI). A differential effect by sex has not been empirically established. Methods: In a prospective population-based cohort study of 23,525 women and 20,725 men younger than 60 years of age at baseline, we followed participants for 12 years for a first AMI. By calculating the proportion of AMI among men with dyslipidemia attributable to the synergism between male sex and dyslipidemia, we assessed the degree to which dyslipidemia is more detrimental for men than for women. Results: Dyslipidemia and male sex enhanced the effect of one another in relation to AMI risk. The proportion of AMI cases among men with dyslipidemia attributable to this synergism alone was 0.46 (95% confidence interval = 0.35 to 0.57) for high total serum cholesterol, 0.23 (0.05 to 0.41) for low high-density lipoprotein (HDL) cholesterol, and 0.52 (0.42 to 0.62) for high non-HDL cholesterol. In contrast, obesity and hypertension were equally detrimental for men and women in relation to AMI risk, with a corresponding attributable proportion of 0.02 (−0.21 to 0.25) and −0.01 (−0.27 to 0.24), respectively. Conclusions: Current clinical guidelines of dyslipidemia management do not distinguish between men and women in relation to primary prevention of AMI. Our results suggest that in middle age, dyslipidemia is much more detrimental for men than for women, and that preventing dyslipidemia has a greater potential to reduce the occurrence of AMI among men.

Abnormal glucose regulation and gender-specific risk of fatal coronary artery disease in the HUNT 1 study.

Abstract Objectives. To assess fatal coronary artery disease (CAD) by gender and glucose regulation status. Design. 47,951 people were followed up according to fatal CAD identified in the National Cause of Death Registry. Gender-effects of fatal CAD in people with impaired glucose regulation (IGR), newly diagnosed diabetes (NDM) or known diabetes (KDM) compared with people with normal glucose regulation (NGR) were calculated using Cox regression. Results. Using NGR as reference, the hazard ratios (HR, 95% confidence intervals) associated with IGR was 1.2 (0.8–1.9) for women and 1.2 (0.9–1.6) for men. The corresponding HRs were 1.6 (1.2–2.2) and 1.4 (1.1.–1.9) for NDM, and 2.5 (2.1–2.8) and 1.8 (1.6–2.1) for KDM. The gender-difference in mortality varied by category (Pinteraction = 0.003). Using women as the reference, the HRs for men were 2.1 (2.0–2.3) for NGR, 1.8 (1.0–3.3) for IGR, 1.6 (1.0–2.5) for NDM, and 1.2 (1.0–1.5) for KDM. Conclusions. Diabetes mellitus, but not IGR, was associated with fatal CAD in both genders. The known gender-difference in CAD mortality was attenuated in people with abnormal glucose regulation, evident already in people with IGR.

Repeated image analyses improves accuracy in assessing arterial flow-mediated dilatation

Objectives. A high degree of variability has been reported regarding the ultrasound-based assessment of flow-mediated dilatation. We wanted to investigate the variability and find out how it might be reduced most efficiently. Design. Brachial artery flow-mediated dilatation was measured by high-resolution ultrasound in 22 healthy adults on two consecutive days. Two observers analysed all images twice. The total variance was split into variance components and estimated hierarchically using the method of restricted maximum likelihood. Results. The relative proportional contributions from intraobserver (residual), interobserver, interpatient and interday variance components, with percentage dilatation as outcome variable, were 0.41, 0.18, 0.25, and 0.15, respectively. Conclusions. The major source of variability when assessing flow-mediated dilatation was found to be intraobserver variability. The simplest way to reduce total variability is for the observer to average results from repeated image analyses. We suggest that three repetitions are sufficient. This will reduce the total variance by 30%.

Predictors of Beneficial Coronary Plaque Changes after Aerobic Exercise.

PURPOSE It has been demonstrated that aerobic exercise induces beneficial changes in coronary atherosclerosis via reduced necrotic core and plaque burden. Clinical factors that may be associated with favorable exercise-induced intracoronary effects are unknown. METHODS This study used post hoc analysis of associations between baseline clinical variables and reductions in coronary necrotic core and plaque burden after aerobic exercise intervention. Coronary plaque characteristics were measured with grayscale and radiofrequency intravascular ultrasound in 36 patients (median age, 58.5 yr; seven women) with stable CAD (SCAD) or non-ST elevation acute coronary syndrome (NSTE-ACS). Screening of clinical variables was performed with random forest analysis followed by multivariate linear regression. RESULTS The only significant clinical variable for necrotic core reduction was clinical presentation of disease (SCAD vs NSTE-ACS, P = 0.011). The changes in necrotic core after exercise were -4.94 mm3 (-10.33; -1.33) in patients with SCAD and 1.03 mm3 (-4.29; 3.71) in patients with NSTE-ACS (P = 0.01). Necrotic core was reduced in 17 patients (94%) with SCAD and eight patients (44%) with NSTE-ACS (P = 0.01). R2 for the model including baseline clinical presentation and baseline necrotic core volume was 0.90. There were no significant explanatory variables for plaque burden reduction. CONCLUSIONS Exercise-induced plaque stabilization via reduced coronary necrotic core may be strongly dependent on clinical presentation of CAD. We hypothesized that an increased proinflammatory load renders patients with NSTE-ACS more resistant to exercise-induced plaque stabilization than patients with SCAD. Furthermore, aerobic exercise may have a particular potential for inducing beneficial effects on coronary atherosclerosis in patients with SCAD compared with patients in the early phase after an acute coronary syndrome.

Reproducibility of grayscale and radiofrequency IVUS data acquisition in stented coronary arteries

Abstract Objectives. Variability in data acquisition from intervened coronary arteries could represent a source of error that has implications for the design of serial stent studies. We assessed inter-pullback reproducibility of volumetric grayscale and radiofrequency intravascular ultrasound (IVUS) data in stented coronary arteries. Design. Fifteen patients with coronary artery lesions treated with stent implantation were included and examined with two separate pullbacks using the Eagle Eye Gold-phased array 20 MHz IVUS catheter (Volcano). The arteries were divided into five segments, giving a total of 150 sub-segments for analyses. Matching of frames was performed using landmarks that were clearly visible in coronary angiography and intravascular pullbacks. Data were analyzed off-line at an independent Corelab. Results. The inter-pullback reproducibility of geometrical data was very good for non-stented segments with relative differences less than 5% between pullbacks for lumen-, vessel-, and plaque volumes. For stented segments reproducibility was poorer with relative differences between pullbacks in the range of 5–10%. The inter-pullback reproducibility of compositional data demonstrated large standard deviations of relative differences, indicating a weaker agreement. Conclusions. Agreements between pullbacks were weaker in stented than those in non-stented segments. Based on our data, future longitudinal IVUS studies in intervened vessels should account for a variability of 5–10% attributed to the acquisition of images.