Chronic Obstructive Pulmonary Disease as a Predictor of Cardiovascular Risk: A Case-Control Study.

Chronic obstructive pulmonary disease (COPD) is a complex multi-morbid disorder with significant cardiac mortality. Current cardiovascular risk prediction models do not include COPD. We investigated whether COPD modifies future cardiovascular risk to determine if it should be considered in risk prediction models.Case-control study using baseline data from two randomized controlled trials performed between 2012 and 2015. Of the 90 eligible subjects, 26 COPD patients with lung hyperinflation were propensity matched for 10-year global cardiovascular risk score (QRISK2) with 26 controls having normal lung function. Patients underwent cardiac magnetic resonance imaging, arterial stiffness and lung function measurements. Differences in pulse wave velocity (PWV), total arterial compliance (TAC) and aortic distensibility were main outcome measures.PWV (mean difference 1.0 m/s, 95% CI 0.02-1.92; p = 0.033) and TAC (mean difference -0.27 mL/m2/mmHg, 95% CI 0.39-0.15; p < 0.001) were adversely affected in COPD compared to the control group. The PWV difference equates to an age, sex and risk-factor adjusted increase in relative risk of cardiovascular events and mortality of 14% and 15%, respectively.There were no differences in aortic distensibility. In the whole cohort (n = 90) QRISK2 (ß = 0.045, p = 0.005) was associated with PWV in multivariate analysis. The relationship between QRISK2 and PWV were modified by COPD, where the interaction term reached significance (p = 0.014). FEV1 (ß = 0.055 (0.027), p = 0.041) and pulse (B = -0.006 (0.002), p = 0.003) were associated with TAC in multivariate analysis.Markers of cardiovascular outcomes are adversely affected in COPD patients with lung hyperinflation compared to controls matched for global cardiovascular risk. Cardiovascular risk algorithms may benefit from the addition of a COPD variable to improve risk prediction and guide management.HAPPY London ClinicalTrials.gov: NCT01911910 and HZC116601; ClinicalTrials.gov: NCT01691885.

Lung Deflation and Cardiovascular Structure and Function in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

RATIONALE: Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. OBJECTIVES: To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. METHODS: Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting ß2-agonist fluticasone furoate/vilanterol 100/25 µg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. MEASUREMENTS AND MAIN RESULTS: There was a 5.8 ml/m(2) (95% confidence interval, 2.74-8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m(2) (P = 0.002) and 2.33 ml/m(2) (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m(2) (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. CONCLUSIONS: Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

Reporting standards in cardiac MRI, CT, and SPECT diagnostic accuracy studies: analysis of the impact of STARD criteria.

AIMS: Diagnostic accuracy studies determine the clinical value of non-invasive cardiac imaging tests. The 'STAndards for the Reporting of Diagnostic accuracy studies' (STARD) were published in 2003 to improve the quality of study reporting. We aimed to assess the reporting quality of cardiac computed tomography (CCT), single positron emission computed tomography (SPECT), and cardiac magnetic resonance (CMR) diagnostic accuracy studies; to evaluate the impact of STARD; and to investigate the relationships between reporting quality, journal impact factor, and study citation index. METHODS AND RESULTS: We randomly generated six groups of 50 diagnostic accuracy studies: 'CMR 1995-2002', 'CMR 2004-11', 'CCT 1995-2002', 'CCT 2004-11', 'SPECT 1995-2002', and 'SPECT 2004-11'. The 300 studies were double-read by two blinded reviewers and reporting quality determined by % adherence to the 25 STARD criteria. Reporting quality increased from 65.3% before STARD to 74.1% after (P = 0.003) in CMR studies and from 61.6 to 79.0% (P < 0.001) in CCT studies. SPECT studies showed no significant change: 71.9% before and 71.5% after STARD (P = 0.92). Journals advising authors to refer to STARD had significantly higher impact factors than those that did not (P = 0.03), and journals with above-median impact factors published studies of significantly higher reporting quality (P < 0.001). Since STARD, citation index has not significantly increased (P = 0.14), but, after adjustment for impact factor, reporting quality continues to increase by ∼1.5% each year. CONCLUSION: Reporting standards for diagnostic accuracy studies of non-invasive cardiac imaging are at most satisfactory and have improved since the introduction of STARD. Adherence to STARD should be mandatory for authors of diagnostic accuracy studies.

Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms?

In the majority of cases, asthma and chronic obstructive pulmonary disease (COPD) are two clearly distinct disease entities. However, in some patients there may be significant overlap between the two conditions. This constitutes an important area of concern because these patients are generally excluded from randomised controlled trials (mostly because of smoking history in the case of asthma or because of significant bronchodilator reversibility in the case of COPD). As a result, their pathobiology, prognosis and response to therapy are largely unknown. This may lead to suboptimal management and can limit the development of more personalised therapeutic options. Emerging genetic and molecular information coupled with new bioinformatics capabilities provide novel information that can pave the way towards a new taxonomy of airway diseases. In this paper we question the current value of the terms 'asthma' and 'COPD' as still useful diagnostic labels; discuss the scientific and clinical progress made over the past few years towards unravelling the complexity of airway diseases, from the definition of clinical phenotypes and endotypes to a better understanding of cellular and molecular networks as key pathogenic elements of human diseases (so-called systems medicine); and summarise a number of ongoing studies with the potential to move the field towards a new taxonomy of airways diseases and, hopefully, a more personalised approach to medicine, in which the focus will shift from the current goal of treating diseases as best as possible to the so-called P4 medicine, a new type of medicine that is predictive, preventive, personalised and participatory.

Reproducibility of arterial stiffness and wave reflections in chronic obstructive pulmonary disease: the contribution of lung hyperinflation and a comparison of techniques.

Significant cardiovascular morbidity and mortality exists in chronic obstructive pulmonary disease (COPD). Arterial stiffness is raised in COPD and may be a mechanistic link. Non-invasive assessment of arterial stiffness has the potential to be a surrogate outcome measure, although no reproducibility data exists in COPD patients. Two studies (23 and 33 COPD patients) were undertaken to 1) assess the Vicorder reproducibility of carotid-femoral pulse wave velocity and Augmentation index in COPD; 2) compare it to SphygmoCor; and 3) assess the contribution of lung hyperinflation to measurement variability. There were excellent correlations and good agreement between repeat Vicorder measurements for carotid-femoral pulse wave velocity (r = 0.96 (p < 0.001); mean difference ±SD = -0.03 ± 0.36 m/s (p = 0.65); co-efficient of reproducibility = 4.02%; limits of agreement = -0.68-0.75 m/s). Augmentation index significantly correlated (r = 0.736 (p < 0.001); mean difference ±SD = 0.72 ± 4.86% (p = 0.48), however limits of agreement were only 10.42-9.02%, with co-efficient of reproducibility of 27.93%. Comparing devices, Vicorder values were lower but there was satisfactory agreement. There were no correlation between lung hyperinflation (as measured by residual volume percent predicted, total lung capacity percent predicted or the ratio of inspiratory capacity to residual volume) and variability of measurements in either study. In COPD, measurement of carotid-femoral pulse wave velocity is highly reproducible, not affected by lung hyperinflation and suitable as a surrogate endpoint in research studies. Day-to-day variation in augmentation index highlights the importance of such studies prior to the planning and undertaking of clinical COPD research.

Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease?

Significant cardiac morbidity and mortality exists in patients with COPD. Shared risk factors include age, smoking history and exposure to air pollution and passive smoke. Although the inappropriate under-prescribing of ß-blockers contributes, it is now appreciated that the observed cardiac risk is not only due to smoking and conventional cardiovascular risk factors, but also other independent factors. A number of hypotheses exist for the increased cardiovascular morbidity and mortality seen in COPD including inflammation, pulmonary hypertension, lung hyperinflation and shared genetics models. Mounting evidence from large randomised controlled trials suggests that COPD treatment may be cardio-protective. We review the current evidence supporting the aforementioned hypotheses and how their modulation may prevent cardiovascular morbidity and mortality in COPD. The persisting underdiagnosis of COPD may have significant consequences. Further mechanistic studies identifying the onset and impact of individual interventions will develop our understanding of this emerging and highly relevant clinical field.