Aims To test whether the efficacy and safety of the selective heart rate‐reducing agent ivabradine changes according to age in chronic heart failure (HF) patients. Methods and results The ivabradine and placebo arms of SHIFT, which enrolled 6505 chronic HF patients, were combined and age distribution was divided by quartiles to give four groups (<53 years, n = 1522; 53 to <60 years, n = 1521; 60 to <69 years, n = 1750; and ≥69 years, n = 1712). The effects of ivabradine on cardiovascular outcomes, changes in heart rate, and adverse events, particularly bradycardia, were evaluated according to age group. A subgroup (602 patients) underwent 24 h ambulatory ECG Holter monitoring. The relative risk of the primary endpoint (cardiovascular death or hospitalization for worsening HF) was reduced by ivabradine in all age groups, ranging from 38% [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.50–0.78, P < 0.001] in the youngest patients <53 years to 16% (HR 0.84, 95% CI 0.71–0.99, P = 0.035) in the oldest patients ≥69 years. Ivabradine up‐titration reduced heart rate similarly in all age groups, by 11 b.p.m. As anticipated, bradycardia and phosphenes occurred more frequently with ivabradine, at a similar rate whatever the age. In the Holter substudy, there were no episodes of severe bradycardia and no clinically relevant pauses with ivabradine in any age group. Conclusions Age does not limit the appropriate use of ivabradine in patients with chronic HF and systolic dysfunction. The safety and efficacy of ivabradine are comparable across all age groups.

BackgroundHeart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist, with undefined prognostic and therapeutic implications. We investigated clinical profile and outcomes of patients with chronic HF and COPD, notably the efficacy and safety of ivabradine, a heart rate-reducing agent.Methods6505 ambulatory patients, in sinus rhythm, heart rate ≥70bpm and stable systolic HF were randomised to placebo or ivabradine (2.5 to 7.5mg bid). Multivariate Cox model analyses were performed to compare the COPD (n=730) and non-COPD subgroups, and the ivabradine and placebo treatment effects.ResultsCOPD patients were older and had a poorer risk profile. Beta-blockers were prescribed to 69% of COPD patients and 92% of non-COPD patients. The primary endpoint (PEP) and its component, hospitalisation for worsening HF, were more frequent in COPD patients (HRs f, 1.22 [p=0.006]; and 1.34 [p<0.001]) respectively, but relative risk was reduced similarly by ivabradine in both COPD (14%, and 17%) and non-COPD (18% and 27%) patients (p interaction=0.82, and 0.53, respectively). Similar effect was noted also for cardiovascular death. Adverse events were more common in COPD patients, but similar in treatment subgroups. Bradycardia occurred more frequently in ivabradine subgroups, with similar incidence in patients with or without COPD.ConclusionsThe association of COPD and HF results in a worse prognosis, and COPD represents a barrier to optimisation of beta-blocker therapy. Ivabradine is similarly effective and safe in chronic HF patients with or without COPD, and can be safely combined with beta-blockers in COPD

Background: Anxiety and insomnia are associated with cardiovascular (CV) symptoms. We assessed whether the relation between anxiety and CV symptoms is modulated by insomnia. Methods: Independently living women (n = 1,440; mean age = 59.36 ± 6.53 years) were recruited by cluster sampling technique. We obtained data on demographic characteristics, health beliefs, access to health care, CV symptoms, sleep, stress and anxiety levels. Results: Overall, 56% of the sample reported insomnia; 46% reported CV symptoms, and 54% were highly anxious. There was a greater likelihood for highly anxious women and those experiencing insomnia to report CV symptoms (rs = 0.31* and rs = 0.32*, respectively). In logistic regression analysis, the adjusted odds ratios for reporting CV symptoms were 1.39 for patients with insomnia and 2.79 for those with anxiety. With control for insomnia, we observed a 3-fold reduction in the magnitude of the association between anxiety and CV symptoms (rp = 0.09*). Stepwise adjustments for sociodemographic factors, CV risk markers, and factors anchoring health beliefs and access to health care showed lesser impact on the relationships. With simultaneous control for those covariates, the correlation was rp = 0.13*; * p < 0.01. Conclusion: The association of CV symptoms with anxiety is partly accounted for by insomnia.

A body of epidemiologic and clinical evidence dating back to the early 1960s establishes the relationships between sleep apnea and cardiovascular disease (CVD). Individuals with obstructive sleep apnea, the most common type of sleep-disordered breathing, are at increased risk for coronary artery disease, congestive heart failure, and stroke. Evidence that treatment of sleep apnea with continuous positive airway pressure reduces blood pressure, improves left ventricular systolic function, and diminishes platelet activation further supports linkage between obstructive sleep apnea and CVD. Notwithstanding, complex associations between these two conditions remain largely unexplained due to dearth of systematic experimental studies. Arguably, several intermediary mechanisms including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress might be involved. Other abnormalities such as dysfunctions in coagulation factors, endothelial damage, platelet activation, and increased systemic inflammation might also play a fundamental role. This review examines evidence for the associations between obstructive sleep apnea and CVD and suggested underlying anatomical and physiological mechanisms. Specific issues pertaining to definition, prevalence, diagnosis, and treatment of sleep apnea are also discussed. Consistent with rising interest in the potential role of the metabolic syndrome, this review explores the hypothesized mediating effects of each of the components of the metabolic syndrome.

s: XIVth Congress of the Pan-American League of Associations for Rheumatology: CATEGORY: NSAIDs and Other Antirheumatic Drugs

Recent studies suggest that pathological alterations of the myocardial extracellular matrix (ECM) are central to development of heart failure in regurgitant valvular diseases. The specific form of these changes, as exemplified by studies in experimental and clinical aortic regurgitation (AR), include hyperproduction of glycoproteins (specifically including fibronectin), which may disorder force transmission and interfere with normal contractility, and synthesis suppression and, perhaps, abnormal degradation, of collagen, preventing optimal resistance to left ventricular dilatation. Cellular-molecular pathways transducing the strains of AR to these abnormalities now are being identified. They suggest possibly beneficial pharmacologic interventions and also the potential harm of certain commonly used anti -hypertensive-"vasodilating" drugs.