Cardiovascular phenotype of long-term anabolic-androgenic steroid abusers compared with strength-trained athletes.

INTRODUCTION: Abuse of anabolic-androgenic steroids (AAS) has been linked to a variety of different cardiovascular (CV) side effects, but still the clinical effects of AAS abuse on CV risk are not clear. The aim of this study was to assess the CV phenotype of a large cohort of men with long-term AAS use compared with strength-trained athletes without AAS use. METHODS: Fifty one strength-trained men with ≥3 years of AAS use was compared with twenty one strength-trained competing athletes. We verified substance abuse and non-abuse by blood and urine analyses. The participants underwent comprehensive CV evaluation including laboratory analyses, 12-lead ECG with measurement of QT dispersion, exercise ECG, 24 h ECG with analyses of heart rate variability, signal averaged ECG, basic transthoracic echocardiography, and coronary computed tomography angiography (CCTA). RESULTS: Hemoglobin levels and hematocrit were higher among the AAS users compared with non-users (16.8 vs. 15.0 g/dl, and 0.50% vs. 0.44%, respectively, both p < 0.01) and HDL cholesterol significantly lower (0.69 vs. 1.25 mmol/L, p < 0.01). Maximal exercise capacity was 270 and 280 W in the AAS and the non-user group, respectively (p = 0.04). Echocardiography showed thicker intraventricular septum and left ventricular (LV) posterior wall among AAS users (p < 0.01 for both), while LV ejection fraction was lower (50 vs. 54%, p = 0.02). Seven AAS users (17%) had evidence of coronary artery disease on CCTA. There were no differences in ECG measures between the groups. CONCLUSIONS: A divergent CV phenotype dominated by increased CV risk, accelerated coronary artery disease, and concentric myocardial hypertrophy was revealed among the AAS users.

Quality of life and psychological outcomes of body-weight supported locomotor training in spinal cord injured persons with long-standing incomplete lesions.

STUDY DESIGN: Health-related quality of life (HRQOL) data from two parallel independent single-blinded controlled randomized studies of manual (Study 1) and robotic (Study 2) locomotor training were combined (ClinicalTrials.gov #NCT00854555). OBJECTIVE: To assess effects of body-weight supported locomotor training (BWSLT) programs on HRQOL in persons with long-standing motor incomplete spinal cord injury and poor walking function. SETTINGS: Two inpatient rehabilitation facilities and one outpatient clinic in Norway. METHODS: Data were merged into intervention (locomotor training 60 days) or control group ("usual care"). Participants completed questionnaires before randomization and 2-4 weeks after the study period, including demographic characteristics, HRQOL (36-Item Short-Form Health Status Survey, SF-36), physical activity (The International Physical Activity Questionnaire Short Form, IPAQ-SF), exercise barrier self-efficacy (EBSE), and motivation for training (Behavioral Regulation in Exercise Questionnaire, BREQ). Physical outcomes i.e., Lower extremity motor score (LEMS) was assessed. The main outcome was change in HRQOL. Secondary outcomes included changes in IPAQ-SF, EBSE, BREQ, and physical outcomes. RESULTS: We recruited 37 of 60 predetermined participants. They were autonomously motivated with high baseline physical activity. BWSLT with manual or robot assistance did not improve HRQOL, though LEMS increased in the BWSLT group compared with control group. CONCLUSIONS: The study was underpowered due to recruitment problems. The training programs seem to benefit LEMS, but not other physical outcomes, and had minimal effects on HRQOL, EBSE, and motivation. Autonomous motivation and high physical activity prior to the study possibly limited the attainable outcome benefits, in addition to limitations due to poor baseline physical function.

Ten-year prediction of cardiovascular disease in healthy Norwegian men, based on NORRISK-2. / Tiårsprediksjon av hjerte- og karsykdom hos friske norske menn basert på NORRISK-2.

BACKGROUND: Norwegian guidelines for primary prevention of cardiovascular disease recommend the use of the NORRISK-2 risk model, with some additions. We wished to investigate whether NORRISK-2 could predict cardiovascular disease in healthy Norwegian men who took part in the Oslo Ischaemia Study. MATERIAL: NORRISK-2 scores were calculated for 2 014 men in the age group 40-60 years who were included in the Oslo Ischaemia Study in 1972-75. Cox regression analyses were used to calculate the hazard ratio for death and cardiovascular disease within ten years of the participants' initial assessment. RESULTS: No participant was lost to follow-up of the 2 014 men, 125 died in the first ten years after inclusion, 61 of whom died from cardiovascular disease. Those who died were older than those who survived, with a larger proportion of daily smokers, and they had higher systolic blood pressure and resting pulse, increased total cholesterol and lower physical fitness. The majority of those who died from acute myocardial infarction and ischaemic stroke within ten years were classified in the high-risk group in NORRISK-2. INTERPRETATION: NORRISK-2 satisfactorily identified the high-risk persons in this cohort of healthy, middle-aged Norwegian men. This supports use of the Norwegian guidelines in the decision on possible primary protection against cardiovascular disease.

Change in Cardiorespiratory Fitness and Risk of Stroke and Death: Long-Term Follow-Up of Healthy Middle-Aged Men.

Background and Purpose- Low cardiorespiratory fitness is associated with increased risk of cardiovascular disease. The present study aims to assess whether change of fitness over time has any impact on long-term risk of stroke and death. Methods- We recruited healthy men aged 40 to 59 years in 1972 to 1975, and followed them until 2007. Physical fitness was assessed with a bicycle ECG test at baseline and again at 7 years, by dividing the total exercise work by body weight. Participants were categorized as remained fit, became unfit, remained unfit, or became fit, depending on whether fitness remained or crossed the median values from baseline to the 7-year visit. Outcome data were collected up to 35 years, from study visits, hospital records, and the National Cause of Death Registry. Risks of stroke and death were estimated by Cox regression analyses and expressed as hazard ratios (HRs) with 95% CIs. Results- Of 2014 participants, 1403 were assessed both at baseline and again at 7 years, and were followed for a mean of 23.6 years. Compared with the became unfit group, risk of stroke was 0.85 (0.54-1.36) for the remained unfit, 0.43 (0.28-0.67) for the remained fit, and 0.34 (0.17-0.67) for the became fit group. For all-cause death, risks were 0.99 (0.76-1.29), 0.57 (0.45-0.74), and 0.65 (0.46-0.90), respectively. Among those with high fitness at baseline, the became unfit group had a significantly higher risk of stroke (HR, 2.35; CI, 1.49-3.63) and death (HR, 1.74; CI, 1.35-2.23) than those who remained fit. Among those who had low fitness at baseline, the became fit group had a significantly lower risk of stroke (HR, 0.40; CI, 0.21-0.72) and death (HR, 0.66; CI, 0.50-0.85) than participants in the remained unfit group. Conclusions- Cardiorespiratory fitness at baseline and change in fitness was associated with large changes in long-term risk of stroke and death. These findings support the encouragement of regular exercise as a stroke prevention strategy.

In juvenile dermatomyositis, heart rate variability is reduced, and associated with both cardiac dysfunction and markers of inflammation: a cross-sectional study median 13.5 years after symptom onset.

OBJECTIVES: Low heart rate variability (HRV) is a well-established predictor of cardiac death. The aim of this study was to investigate arrhythmias and HRV in patients with JDM, and associations between HRV and inflammatory markers, echocardiographic measurements and disease parameters. METHODS: Fifty-five patients with JDM were examined 2-34 years (median 13.5 years) after disease onset, and compared with 55 age and sex matched controls. Holter ECG monitoring and echocardiography were analysed blinded to patient information. Arrhythmia and HRV (six parameters) were analysed by standard software, finally adjudicated by an experienced cardiologist. Markers of inflammation (ESR, high sensitivity (hs)CRP and cytokines) were analysed. Disease activity and organ damage were assessed by clinical examination at follow-up and retrospectively by chart review. RESULTS: In two out of six HRV parameters, JDM patients had lower values than controls. No difference in arrhythmias was found between the groups. In patients, but not in controls, there were significant negative correlations between five out of six HRV parameters, and ESR and hsCRP (Spearman correlation coefficient, -0.306 to -0.470; P, 0.023 to <0.001). Also, in patients, negative correlations were found between three out of six HRV parameters and systolic and diastolic function. Active disease and low HRV were associated. Patients with hsCRP in the highest quartile (Q4) had lower HRV in all parameters compared with those in pooled Q1-3 (P < 0.001). CONCLUSION: JDM patients had reduced HRV, which was associated with elevated inflammatory markers, active disease and reduced myocardial function. This suggests reduced vagal control of the heart; further studies are needed to determine whether this is also associated with cardiac morbidity or mortality.

Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation.

AIMS: Rate control of atrial fibrillation (AF) has become a main treatment modality, but we need more knowledge regarding the different drugs used for this purpose. In this study, we aimed to compare the effect of four common rate-reducing drugs on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent AF. METHODS AND RESULTS: We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF and normal left ventricular function in a randomized, cross-over, investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered o.d. for 3 weeks. At baseline and on the last day of each treatment period, the patients underwent a maximal cardiopulmonary exercise test and blood samples were obtained at rest and at peak exercise. The exercise capacity (peak VO2) was significantly lower during treatment with metoprolol and carvedilol compared with baseline (no treatment) or treatment with diltiazem and verapamil (P < 0.001 for all). Compared with baseline, treatment with diltiazem and verapamil significantly reduced the NT-proBNP levels both at rest and at peak exercise, whereas treatment with metoprolol and carvedilol increased the levels (P < 0.05 for all). CONCLUSION: Rate-reducing treatment with diltiazem or verapamil preserved exercise capacity and reduced levels of NT-proBNP compared with baseline, whereas treatment with metoprolol or carvedilol reduced the exercise capacity and increased levels of NT-proBNP.

[A man in his eighties with recurrent syncope]. / En mann i 80-årene med gjentatte synkoper.

BACKGROUND: Syncope is usually a benign event that affects up to 50% of people over a lifetime, needing no extensive examination. The challenge is to diagnose the few with underlying life-threatening disease in need of immediate medical attention. Guidelines are clear, but unfortunately, clinical practice does not always follow recommendations, as illustrated by this case report. CASE PRESENTATION: A diabetic, hypertensive male in his eighties had a myocardial infarction in his medical history. He presented to his GP with recurrent syncopal episodes that had occurred while erect and in motion. Physical examination was found to be normal for his age, and he was referred to a cardiologist and seen three months later. An ECG showed sinus rhythm and a previous inferior wall myocardial infarction. A 24-hour ECG recorder was fitted, and a consultation was scheduled for the next day. At home the patient died. The ECG recording revealed sinus rhythm with increasing depression of the ST segment, followed by rapidly conducted atrial fibrillation, and then rapid ventricular tachycardia followed by terminal ventricular fibrillation. INTERPRETATION: A patient with a history where there is suspicion of cardiac syncope should be immediately and intensively examined when presenting to the healthcare services.

Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients.

Methadone (R,S-methadone) can prolong the QT interval. R-methadone inhibits cardiac potassium channel function less than S-methadone. We tested if switching from methadone to R-methadone would reduce corrected QT (QTc) intervals in methadone maintenance treatment (MMT) patients. Nine patients, with automatically read QTc intervals ≥450 ms, were required to detect a 20 ms (clinically relevant) reduction in QTc intervals with 15 ms standard deviation (SD) and 90% power. Nine stabilized MMT patients, using median (range) 70 (40-120) mg methadone, were included. Data (ECG recordings, serum samples, and withdrawal symptoms) were collected both before drug intake (Cmin ) and at 3 h after drug intake (Cmax ), and were collected on the day before the switch from methadone to equipotent R-methadone dose and at 14 and 28 days after the switch. A cardiologist calculated QTc intervals retrospectively. Serum electrolytes and methadone concentrations were measured. Mean QTc intervals at Cmin were 472 ms and 422 ms on methadone (automatically and manually read) and 414 ms on R-methadone (manually read). Mean (SD) change in QTc intervals was -8 (10) ms (p = 0.047) at Cmin but non-significant at Cmax . R-methadone showed a concentration-dependent relationship with QTc intervals. Switching to R-methadone reduced QTc intervals, but far less than the 20 ms considered clinically relevant.

[Cardiac screening of young athletes]. / Hjertescreening av unge idrettsutøvere.

BACKGROUND: Young athletes are at an increased risk of sudden cardiac death compared to others. Cardiac screening has been proposed to prevent deaths. We wished to review the evidence for cardiac screening of young athletes. METHOD: We have conducted a literature search in PubMed on sudden cardiac death in young athletes, using a combination of search terms related to screening, incidence, cost efficiency and recommendations, supplemented by secondary references and articles from our own archive. RESULTS: Published studies utilise a variety of definitions of athlete and sudden death, and some studies also include cardiac arrest with subsequent successful resuscitation. Retrospective studies, often based on media searches, remain the most common form. The cause of death is not invariably determined by an autopsy. Recommendations in favour of screening are based on studies of limited quality and on the personal, often regional, experiences of experts. INTERPRETATION: The differences in study methods result in uncertain incidence figures. The estimates of cost efficiency are therefore questionable. To improve the quality of knowledge, standardised methods need to be devised, ideally also including a register of cardiac arrest in children and young people. To date, we have insufficient knowledge to recommend mandatory cardiac screening with ECG in Norway. Should this be introduced, it should be differentiated according to gender, type of sport and competition level. Cost efficiency could probably be improved with the aid of standardised questionnaires and a standardised interpretation of ECG among athletes.

Temporary emergency pacing--an orphan in district hospitals.

This editorial discusses a report on the 1 year experience with temporary pacing, especially in the emergency setting, in several Norwegian district hospitals. The vast majority of the patients received transvenous temporary pacing, and the majority of leads were placed by noncardiologists. The procedure times were long and complications were frequent. The organization of emergency pacing is discussed, and we suggest that unless qualified physicians can establish transvenous pacing, the patients who need that should be transferred with transcutaneous pacing as back-up during transport to a hospital with more available competence. Ideally, those who need pacing immediately, including those who need permanent pacing, should be offered permanent implantation on a 24 hours/7 days per week base.

Impact of alcohol habits and smoking on the risk of new-onset atrial fibrillation in hypertensive patients with ECG left ventricular hypertrophy: the LIFE study.

BACKGROUND: The incidence of new-onset atrial fibrillation (AF) is increased by uncontrolled hypertension, and antihypertensive treatment reduces new-onset AF. However, it is unclear whether alcohol intake and smoking influence the risk of new-onset AF during antihypertensive treatment. METHODS: In the Losartan Intervention For Endpoint reduction in Hypertension (LIFE) study, a double-blinded, randomized, parallel-group study, 9193 hypertensive patients with electrocardiogram (ECG)-documented left ventricular hypertrophy (LVH), randomized to once-daily losartan- or atenolol-based antihypertensive therapy were followed for a mean of 4.8 years. At baseline, 8831 patients (54% women, mean age 67 years, mean blood pressure 174/98 mmHg after placebo run-in) had neither a history of AF nor AF on ECG, and they were thus at risk of developing this condition during the study. RESULTS: New-onset AF occurred in 353 (4%) patients. Univariate Cox analyses showed that intake of alcohol > 10 units/week compared with less or no alcohol intake predicted new-onset AF (Hazard ratio, HR = 1.60 [95% CI 1.02-2.51], p = 0.043). Multivariate Cox regression analysis showed that intake of alcohol > 10 units/week predicted new-onset AF (p = 0.010) independently of most other univariate predictors, except when also baseline serum cholesterol, serum potassium and urinary albumin/creatinine ratio were included in the model (HR = 1.60 [95% CI 0.94-2.72], p = 0.081). Impact of smoking was not significant in Cox univariate or multivariate analyses, and there were no significant interactions between high alcohol intake and either smoking or gender on the risk of getting AF. CONCLUSIONS: Up to 10 drinks of alcohol per week appears to be safe with respect to the risk for AF in hypertensive patients with LVH. Our data suggest that alcohol intake above this level may be marginally deleterious, while no effect of smoking on risk of AF was detected in hypertensive patients with LVH.

[Resting pulse rate as an indicator of health and disease]. / Hva sier hvilepulsen om helse og sykdom?

BACKGROUND: The resting pulse rate appears to be an independent cardiovascular risk factor. The paper reviews the scientific evidence in support of this assertion and discusses how the findings of this simple examination may be put to clinical use. METHOD: We have evaluated the relationship between resting pulse rate, cardiovascular disease and mortality based on evidence retrieved by a search in the Medline database. RESULTS: The resting pulse rate varies with physical fitness, and high intensity training can decrease the resting pulse. A high resting pulse rate is associated with an elevated risk of cardiovascular disease, and a poorer prognosis in established cardiovascular disease. The relationship between a high resting pulse and death from cardiovascular disease can be explained by well-known pathophysiological mechanisms, but more evidence is needed. In particular, we do not know why the associations between pulse rate and health are weaker in females. Physical exercise is beneficial in prevention and often also in the treatment of cardiovascular disease. We do not yet know how much of the beneficial effects of exercise are mediated through a lowered resting pulse. INTERPRETATION: Taking the resting pulse should form part of prophylactic health monitoring procedures the same way as the monitoring of other cardiovascular risk markers such as blood pressure, lipids, smoking status and weight. Among patients with established cardiovascular disease, the resting pulse rate is an important prognostic marker. An elevated resting pulse rate might be an incitement to recommend increased physical activity.

Atrial fibrillation, physical activity and endurance training.

INTRODUCTION: Clinical practice and the results of some studies may indicate that physical exercise in the form of endurance training may influence the development of atrial fibrillation (AF). The aim of this paper is to evaluate the scientific background for the hypothesis that there is a connection between physical activity and AF. MATERIAL AND METHOD: This paper is a review article based on searches in PubMed on specific topics, limited to the period 1995 through March 2011. We found 17 original articles and three relatively recent reviews. Each was read by at least two of the authors and then discussed. Seven of the original articles were excluded for methodological reasons, and we therefore discuss the other ten. RESULTS: We found support for the hypothesis that systematic high intensity endurance training such as running can increase the risk of AF, whereas the studies provide no evidence that less intensive physical exercise such as walking increases the risk. Several of the studies have methodological weaknesses. INTERPRETATION: Important questions remain unanswered. There is a need for more studies that can shed light on the connection between training intensity, total volume of intensive endurance training, age-related changes and AF. Studies that include women are also needed.

Novel insights into stroke risk beyond resting and maximal bicycle exercise systolic blood pressure.

OBJECTIVE: Previous research has shown an association between moderate workload exercise blood pressure (BP) and coronary disease, whereas maximal exercise BP is associated with stroke. We aimed to investigate the association between the increase in BP during maximal exercise and the long-term risk of stroke in healthy, middle-aged men. METHODS: Two thousand and fourteen men were included in the Oslo Ischemia Study in the 1970s. In the present study, we examined baseline data of the 1392 participants who remained healthy and performed bicycle exercise tests both at baseline and 7 years later. Cox proportional hazard was used to assess the risk of stroke in participants divided into quartiles based on the difference between resting and maximal workload SBP (ΔSBP) at baseline, adjusting for resting BP, age, smoking, serum cholesterol and physical fitness. Follow-up was until the first ischemic or hemorrhagic stroke through 35 years. RESULTS: There were 195 incident strokes; 174 (89%) were ischemic. In univariate analyses, there were significant positive correlations between age, resting SBP, resting DBP and SBP at moderate and maximal workload, and risk of stroke. In the multivariate analysis, there was a 2.6-fold (P < 0.0001) increase in risk of stroke in ΔSBP quartile 4 (ΔSBP > 99 mmHg) compared with ΔSBP quartile 2 (ΔSBP 73-85 mmHg), which had the lowest risk of stroke. ΔSBP quartile 1 had a 1.7-fold (P = 0.02) increased risk compared with quartile 2, suggesting a J-shaped association to stroke risk. CONCLUSION: Stroke risk increased with increasing difference between resting and maximal exercise SBP, independent of BP at rest, suggesting that an exaggerated BP response to physical exercise may be an independent predictor of stroke.