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      Cardiovascular disease and COPD: dangerous liaisons?

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      1 , 2 , , 3 , 4 , 5
      European Respiratory Review
      European Respiratory Society

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          Abstract

          Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently occur together and their coexistence is associated with worse outcomes than either condition alone. Pathophysiological links between COPD and CVD include lung hyperinflation, systemic inflammation and COPD exacerbations. COPD treatments may produce beneficial cardiovascular (CV) effects, such as long-acting bronchodilators, which are associated with improvements in arterial stiffness, pulmonary vasoconstriction, and cardiac function. However, data are limited regarding whether these translate into benefits in CV outcomes. Some studies have suggested that treatment with long-acting β 2-agonists and long-acting muscarinic antagonists leads to an increase in the risk of CV events, particularly at treatment initiation, although the safety profile of these agents with prolonged use appears reassuring. Some CV medications may have a beneficial impact on COPD outcomes, but there have been concerns about β-blocker use leading to bronchospasm in COPD, which may result in patients not receiving guideline-recommended treatment. However, there are few data suggesting harm with these agents and patients should not be denied β-blockers if required. Clearer recommendations are necessary regarding the identification and management of comorbid CVD in patients with COPD in order to facilitate early intervention and appropriate treatment.

          Abstract

          CVD and COPD are often comorbid. Their pathophysiology and treatment may affect each other and health outcomes. http://ow.ly/v18p30lxmms

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          Most cited references200

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          2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

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            Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure

            We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients. In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes. The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group. LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).
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              Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study

              Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell’s C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.

                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 September 2018
                03 October 2018
                : 27
                : 149
                : 180057
                Affiliations
                [1 ]Dept of Medicine, University of Kiel, Kiel, Germany
                [2 ]Lung Clinic Großhansdorf, Airway Research Center North (ARCN), Groβhansdorf, Germany
                [3 ]Centre for Inflammation and Tissue Repair, Division of Medicine, University College London, London, UK
                [4 ]Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada
                [5 ]Dept of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada
                Author notes
                Klaus F. Rabe, LungenClinic Großhansdorf, Airway Research Center North, Woehrendamm 80, Großhansdorf 22927, Germany. E-mail: k.f.rabe@ 123456lungenclinic.de
                Article
                ERR-0057-2018
                10.1183/16000617.0057-2018
                9488649
                30282634
                45161ff9-c3f1-436a-81f4-f94a0686df20
                Copyright ©ERS 2018.

                ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 19 June 2018
                : 20 August 2018
                Funding
                Funded by: Novartis, doi 10.13039/100004336;
                Categories
                Review
                1

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