Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

Cardiac patients after an acute event and/or with chronic heart disease deserve special attention to restore their quality of life and to maintain or improve functional capacity. They require counselling to avoid recurrence through a combination of adherence to a medication plan and adoption of a healthy lifestyle. These secondary prevention targets are included in the overall goal of cardiac rehabilitation (CR). Cardiac rehabilitation can be viewed as the clinical application of preventive care by means of a professional multi-disciplinary integrated approach for comprehensive risk reduction and global long-term care of cardiac patients. The CR approach is delivered in tandem with a flexible follow-up strategy and easy access to a specialized team. To promote implementation of cardiac prevention and rehabilitation, the CR Section of the EACPR (European Association of Cardiovascular Prevention and Rehabilitation) has recently completed a Position Paper, entitled 'Secondary prevention through cardiac rehabilitation: A condition-oriented approach'. Components of multidisciplinary CR for seven clinical presentations have been addressed. Components include patient assessment, physical activity counselling, exercise training, diet/nutritional counselling, weight control management, lipid management, blood pressure monitoring, smoking cessation, and psychosocial management. Cardiac rehabilitation services are by definition multi-factorial and comprehensive, with physical activity counselling and exercise training as central components in all rehabilitation and preventive interventions. Many of the risk factor improvements occurring in CR can be mediated through exercise training programmes. This call-for-action paper presents the key components of a CR programme: physical activity counselling and exercise training. It summarizes current evidence-based best practice for the wide range of patient presentations of interest to the general cardiology community.

Effects of thoracic epidural anesthesia on hemodynamics and global oxygen transport in ovine endotoxemia

Besides providing effective analgesia, thoracic epidural anesthesia (TEA) has been shown to decrease perioperative morbidity and mortality. Because of its vasodilatory properties in association with the sympathetic blockade, however, TEA may potentially aggravate cardiovascular dysfunctions resulting from sepsis and systemic inflammatory response syndrome. The objective of the present study was to assess the effects of TEA on hemodynamics, global oxygen transport, and renal function in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 18), Salmonella typhosa endotoxin was centrally infused at incremental doses to induce and maintain a hypotensive-hypodynamic circulation using an established protocol. The animals were then randomly assigned to one of two groups. In the treatment group, continuous TEA was initiated with 0.1 mL.kg of 0.125% bupivacaine at the onset of endotoxemia and maintained with 0.1 mL.kg.h. In the control group, the same amount of isotonic sodium chloride solution was injected through the epidural catheter. In the animals surviving the entire experiment (n = 7 per group), cardiac index and mean arterial pressure decreased in a dose-dependent manner during endotoxin infusion. In the TEA group, neither systemic hemodynamics nor global oxygen transport were impaired beyond the changes caused by endotoxemia itself. Urinary output was increased in the TEA group as compared with the control group (P < 0.05). In this model of endotoxic shock, TEA improved renal perfusion without affecting cardiopulmonary hemodynamics and global oxygen transport.

Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in children, is associated with obesity and insulin resistance. However, the relationship between NAFLD and cardiovascular risk factors in children is not fully understood. The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children. METHODS AND RESULTS: This case-control study of 150 overweight children with biopsy-proven NAFLD and 150 overweight children without NAFLD compared rates of metabolic syndrome using Adult Treatment Panel III criteria. Cases and controls were well matched in age, sex, and severity of obesity. Children with NAFLD had significantly higher fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure than overweight and obese children without NAFLD. Subjects with NAFLD also had significantly lower high-density lipoprotein cholesterol than controls. After adjustment for age, sex, race, ethnicity, body mass index, and hyperinsulinemia, children with metabolic syndrome had 5.0 (95% confidence interval, 2.6 to 9.7) times the odds of having NAFLD as overweight and obese children without metabolic syndrome. CONCLUSIONS: NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors. The identification of NAFLD in a child should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes.

Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains

We report the characterisation of 27 cardiovascular-related traits in 23 inbred mouse strains. Mice were phenotyped either in response to chronic administration of a single dose of the beta-adrenergic receptor blocker atenolol or under a low and a high dose of the beta-agonist isoproterenol and compared to baseline condition. The robustness of our data is supported by high trait heritabilities (typically H(2)>0.7) and significant correlations of trait values measured in baseline condition with independent multistrain datasets of the Mouse Phenome Database. We then focused on the drug-, dose-, and strain-specific responses to beta-stimulation and beta-blockade of a selection of traits including heart rate, systolic blood pressure, cardiac weight indices, ECG parameters and body weight. Because of the wealth of data accumulated, we applied integrative analyses such as comprehensive bi-clustering to investigate the structure of the response across the different phenotypes, strains and experimental conditions. Information extracted from these analyses is discussed in terms of novelty and biological implications. For example, we observe that traits related to ventricular weight in most strains respond only to the high dose of isoproterenol, while heart rate and atrial weight are already affected by the low dose. Finally, we observe little concordance between strain similarity based on the phenotypes and genotypic relatedness computed from genomic SNP profiles. This indicates that cardiovascular phenotypes are unlikely to segregate according to global phylogeny, but rather be governed by smaller, local differences in the genetic architecture of the various strains.

Psychosocial outcome in cardiovascular rehabilitation of peripheral artery disease and coronary artery disease patients

We investigated patients with a primary diagnosis of peripheral artery disease (n = 69) and coronary heart disease (CAD; n = 520) at baseline and on changes in psychosocial risk factors (depression, anxiety, quality of life, negative and positive affect) during a cardiovascular rehabilitation program. Patients completed psychosocial questionnaires at the beginning and at discharge of a 12-week rehabilitation program. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale (HADS), positive and negative affect with the Global Mood Scale, and health-related quality of life with the SF-36 Health Survey. Patients with PAD showed improvements in anxiety (p < 0.001), negative affect (p < 0.001) and bodily pain (p < 0.001). Patients with CAD reported significant improvements in all measured dimensions (all p-values < 0.001).

Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

A cardiovascular mathematical model of graded head-up tilt

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.

Positive affect moderates the effect of negative affect on cardiovascular disease-related hospitalizations and all-cause mortality after cardiac rehabilitation

BACKGROUND Little is known as to whether negative emotions adversely impact the prognosis of patients who undergo cardiac rehabilitation. We prospectively investigated the predictive value of state negative affect (NA) assessed at discharge from cardiac rehabilitation for prognosis and the moderating role of positive affect (PA) on the effect of NA on outcomes. METHODS A total of 564 cardiac patients (62.49 ± 11.51) completed a comprehensive three-month outpatient cardiac rehabilitation program, filling in the Global Mood Scale (GMS) at discharge. The combined endpoint was cardiovascular disease (CVD)-related hospitalizations plus all-cause mortality at follow-up. Cox regression models estimated the predictive value of NA, as well as the moderating influence of PA on outcomes. Survival models were adjusted for sociodemographic factors, traditional cardiovascular risk factors, and severity of disease. RESULTS During a mean follow-up period of 3.4 years, 71 patients were hospitalized for a CVD-related event and 15 patients died. NA score (range 0-20) was a significant and independent predictor (hazard ratio (HR) 1.091, 95% confidence interval (CI) 1.012-1.175; p = 0.023) with a three-point higher level in NA increasing the relative risk by 9.1%. Furthermore, PA interacted significantly with NA (p < 0.001). The relative risk of poor prognosis with NA was increased in patients with low PA (p = 0.012) but remained unchanged in combination with high PA (p = 0.12). CONCLUSION The combination of NA with low PA was particularly predictive of poor prognosis. Whether reduction of NA and increase of PA, particularly in those with high NA, improves outcome needs to be tested.

Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease

OBJECTIVE This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. METHODS AND RESULTS Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. CONCLUSION Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.

Impact of body mass index on long-term clinical outcomes after second-generation drug eluting stent implantation: Insights from the international global RESOLUTE program

BACKGROUND An increased body mass index (BMI) is associated with a high risk of cardiovascular disease and reduction in life expectancy. However, several studies reported improved clinical outcomes in obese patients treated for cardiovascular diseases. The aim of the present study is to investigate the impact of BMI on long-term clinical outcomes after implantation of zotarolimus eluting stents. METHODS Individual patient data were pooled from the RESOLUTE Clinical Program comprising five trials worldwide. The study population was sorted according to BMI tertiles and clinical outcomes were evaluated at 2-year follow-up. RESULTS Data from a total of 5,127 patients receiving the R-ZES were included in the present study. BMI tertiles were as follow: I tertile (≤ 25.95 kg/m(2) -Low or normal weight) 1,727 patients; II tertile (>25.95 ≤ 29.74 kg/m(2) -overweight) 1,695 patients, and III tertile (>29.74 kg/m(2) -obese) 1,705 patients. At 2-years follow-up no difference was found for patients with high BMI (III tertile) compared with patients with normal or low BMI (I tertile) in terms of target lesion failure (I-III tertile, HR [95% CI] = 0.89 [0.69, 1.14], P = 0.341; major adverse cardiac events (I-III tertile, HR [95% CI] = 0.90 [0.72, 1.14], P = 0.389; cardiac death (I-III tertile, HR [95% CI] = 1.20 [0.73, 1.99], P = 0.476); myocardial infarction (I-III tertile, HR [95% CI] = 0.86 [0.55, 1.35], P = 0.509; clinically-driven target lesion revascularization (I-III tertile, HR [95% CI] = 0.75 [0.53, 1.08], P = 0.123; definite or probable stent thrombosis (I-III tertile, HR [95% CI] = 0.98 [0.49, 1.99], P = 0.964. CONCLUSIONS In the present study, the patients' body mass index was found to have no impact on long-term clinical outcomes after coronary artery interventions.