Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation

Clinical risk factors and atherosclerotic plaque extent to define risk for major events in patients without obstructive coronary artery disease: the long-term coronary computed tomography angiography CONFIRM registry.

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).ConclusionAmong patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both

Evaluation of Functional Condition of Respiratory Muscles of Patients with a Complicated Bronchial Asthma Pathology and Chronic Obstructive Pulmonary Diseases

The aim of the research was to study the functional state of respiratory muscles and neuro-respiratory drive in patients with a combined pathology of bronchial asthma and chronic obstructive pulmonary disease.The functional condition of the respiratory muscles and the tone of the respiratory centre were determined with the help of a device for occlusion spirometry. Also, the patient was observed with a spirometry, a general plethysmography of the body.Materials and methods.140 patients with combined broncho-obstructive pathology, 34 patients with asthma and 17 patients with COPD were examined. Spirometry, general plethysmography of the body and occlusion spirometry were provided for all patients.Results show a decrease in muscle strength of breath in all categories of patients with broncho-obstructive diseases, especially expressed in patients with bronchial asthma and asthma-COPD intersection. The muscle strength of breath was maintained with a significant increase in COPD patients compared with those with bronchial asthma. With increasing broncho-obstruction in patients with asthma-COPD intersection, there was a progressive and reliable decrease in muscle strength for breath and expiration, as well as a tendency to increase neuron respiratory drive. In patients with asthma-COPD intersection with more expressed symptoms revealed a significant and reliable weakening of muscle strength for breath and increased neuro-respiratory drive. During the work were obtained reliable links of the parameters of respiratory muscle strength not only with the parameters of pulmonary volume and bronchial patency, but also with the degree of neutrophilic inflammation in this category of patients.Conclusions The obtained data on failure of the functional state of the respiratory muscles and the neuro-respiratory drive can be used in the development of rehabilitation programs for the management of patients with combined broncho-obstructive pathology

Inhaled corticosteroids versus long-acting beta -agonists for chronic obstructive pulmonary disease (Review).

Long-acting beta(2)-agonists and inhaled corticosteroids can be used as maintenance therapy by patients with moderate to severe chronic obstructive pulmonary disease. These interventions are often taken together in a combination inhaler. However, the relative added value of the two individual components is unclear

The Bidirectional Relationship Between Obstructive Sleep Apnea and Metabolic Disease

Obstructive sleep apnea (OSA) is a common sleep disorder, effecting 17% of the total population and 40–70% of the obese population (1, 2). Multiple studies have identified OSA as a critical risk factor for the development of obesity, diabetes, and cardiovascular diseases (3–5). Moreover, emerging evidence indicates that metabolic disorders can exacerbate OSA, creating a bidirectional relationship between OSA and metabolic physiology. In this review, we explore the relationship between glycemic control, insulin, and leptin as both contributing factors and products of OSA. We conclude that while insulin and leptin action may contribute to the development of OSA, further research is required to determine the mechanistic actions and relative contributions independent of body weight. In addition to increasing our understanding of the etiology, further research into the physiological mechanisms underlying OSA can lead to the development of improved treatment options for individuals with OSA

Telehealthcare for chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease of irreversible airways obstruction in which patients often suffer exacerbations. Sometimes these exacerbations need hospital care: telehealthcare has the potential to reduce admission to hospital when used to administer care to the pateint from within their own home. OBJECTIVES: To review the effectiveness of telehealthcare for COPD compared with usual face‐to‐face care. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, which is derived from systematic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO; last searched January 2010. SELECTION CRITERIA: We selected randomised controlled trials which assessed telehealthcare, defined as follows: healthcare at a distance, involving the communication of data from the patient to the health carer, usually a doctor or nurse, who then processes the information and responds with feedback regarding the management of the illness. The primary outcomes considered were: number of exacerbations, quality of life as recorded by the St George's Respiratory Questionnaire, hospitalisations, emergency department visits and deaths. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion and extracted data. We combined data into forest plots using fixed‐effects modelling as heterogeneity was low (I(2) < 40%). MAIN RESULTS: Ten trials met the inclusion criteria. Telehealthcare was assessed as part of a complex intervention, including nurse case management and other interventions. Telehealthcare was associated with a clinically significant increase in quality of life in two trials with 253 participants (mean difference ‐6.57 (95% confidence interval (CI) ‐13.62 to 0.48); minimum clinically significant difference is a change of ‐4.0), but the confidence interval was wide. Telehealthcare showed a significant reduction in the number of patients with one or more emergency department attendances over 12 months; odds ratio (OR) 0.27 (95% CI 0.11 to 0.66) in three trials with 449 participants, and the OR of having one or more admissions to hospital over 12 months was 0.46 (95% CI 0.33 to 0.65) in six trials with 604 participants. There was no significant difference in the OR for deaths over 12 months for the telehealthcare group as compared to the usual care group in three trials with 503 participants; OR 1.05 (95% CI 0.63 to 1.75). AUTHORS' CONCLUSIONS: Telehealthcare in COPD appears to have a possible impact on the quality of life of patients and the number of times patients attend the emergency department and the hospital. However, further research is needed to clarify precisely its role since the trials included telehealthcare as part of more complex packages

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p &lt; 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p &lt; 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

The contribution of fatigue and sleepiness to depression in patients attending the sleep laboratory for evaluation of obstructive sleep apnea

Purpose: A high prevalence of depressive symptomatology has been reported amongst sufferers of obstructive sleep apnea (OSA), but it remains unclear as to whether this is due to their OSA or other factors associated with the disorder. The current study aimed to assess the incidence and aetiology of depression in a community sample of individuals presenting to the sleep laboratory for diagnostic assessment of OSA. Methods: Forty-five consecutive individuals who presented to the sleep laboratory were recruited; of those, 34 were diagnosed with OSA, and 11 were primary snorers with no clinical or laboratory features of OSA. Nineteen control subjects were also recruited. Patients and controls completed the Beck Depression Inventory, the Profile of Mood States (POMS), and the Epworth Sleepiness Scale to assess their mood and sleepiness, prior to their polysomnography. Results: All patients reported significantly more depressive symptoms compared with healthy controls, regardless of their degree of OSA. There were no significant differences between OSA patients and primary snorers on any of the mood and self-rated sleepiness measures. Depression scores were not significantly associated with any of the nocturnal variables. Regression analysis revealed that the POMS fatigue subscale explained the majority of the variance in subjects' depression scores. Conclusions: Fatigue was the primary predictor of the level of depressive symptoms in patients who attended the sleep laboratory, regardless of the level of severity of sleep disordered breathing. When considering treatment options, practitioners should be aware of the concomitant occurrence of depressive symptoms and fatigue in patients presenting with sleep complaints, which may not be due to a sleep disorder

Combination inhaled steroid and long-acting beta2-agonist versus tiotropium for chronic obstructive pulmonary disease

Background Combination therapy (inhaled corticosteroids and long-acting beta(2)-agonists) and tiotropium are both used in the treatment of chronic obstructive pulmonary disease (COPD). There is uncertainty about the relative benefits and harms of these treatments. Objectives To assess the relative effects of inhaled combination therapy and tiotropium on patients with COPD. Search strategy We searched the Cochrane Airways Group Specialised Register of trials (March 2010) and reference lists of articles. We also contacted authors of the studies.Selection criteriaWe included only parallel, randomised controlled trials comparing inhaled combination corticosteroid and long-acting beta(2)-agonist against inhaled tiotropium bromide. Data collection and analysis Two authors independently assessed trials for inclusion and then extracted data on trial quality and outcome results. We contacted study authors for additional information. Discrepancies were resolved through discussion. Main results One large two year trial (INSPIRE) and two smaller, shorter trials (Dawber 2005; SCO40034) were found. The results from these trials were not pooled. The number of withdrawals from each arm of the INSPIRE trial was large and imbalanced and outcome data was not collected for patients who withdrew, raising concerns about the reliability of data from this study.In INSPIRE, there were more deaths on tiotropium than on fluticasone/salmeterol (Peto OR 0.55; 95% CI 0.33 to 0.93). This was a statistically significant difference, however the number of withdrawals from each of the arms was eleven times larger than the observed number of deaths for participants on fluticasone/salmeterol and seven times larger for participants on tiotropium. There were more all cause hospital admissions in patents on fluticasone/salmeterol than those on tiotropium in INSPIRE (Peto OR 1.32; 95% CI 1.04 to 1.67). There was no statistically significant difference in hospital admissions due to exacerbations, the primary outcome of INSPIRE. There was no significant difference in exacerbations in patients on fluticasone/salmeterol compared to tiotropium. Exacerbations requiring treatment with oral corticosteroids were less frequent in patients on fluticasone/salmeterol (Rate Ratio 0.81; 95% CI 0.67 to 0.99). Conversely exacerbations requiring treatment with antibiotics were more frequent in patients treated with fluticasone/salmeterol (Rate Ratio 1.19; 95% CI 1.02 to 1.38). There were more cases of pneumonia in patients on fluticasone/salmeterol than those on tiotropium (Peto OR 2.13; 95% CI 1.33 to 3.40). Confidence intervals for these outcomes do not reflect the additional uncertainty arising from unknown outcome data for patients who withdrew. Authors' conclusions Since the proportion of missing outcome data compared to the observed outcome data is enough to induce a clinically relevant bias in the intervention effect, the relative efficacy and safety of combined inhalers and tiotropium remains uncertain. Further large, long-term randomised controlled trials comparing combination therapy to tiotropium are required, including adequate follow-up of all participants randomised (similar to the procedures undertaken in TORCH and UPLIFT). Additional studies comparing alternative inhaled LABA/steroid combination therapies with tiotropium are also required