Cardiovascular Risk and Chronic Obstructive Pulmonary Disease

Official title

Cardiovascular Risk and Chronic Obstructive Pulmonary Disease (COPD)

Overview

The principal objective of the study is to measure parameters of inflammation, oxidative stress, and vascular, respiratory, and peripheral muscle function parameters, and identify parameters indicative of evolving cardiovascular risk (CVR) in COPD patients, using multivariate analysis.

Detailed description

Reduced lung function is a major risk factor for cardiovascular mortality (CV), regardless of age, sex and history of smoking. Similarly, CV events are known causes of mortality in patients with chronic obstructive pulmonary disease (COPD). The investigators propose to determine the parameters influencing the evolution of CV risk in a cohort of COPD patients followed over 5 years. For this the investigators will study the role of inflammation, oxidative stress, and vascular, respiratory and peripheral muscle function parameters.

In order to study a sufficient number of patients the investigators propose to group data from two cohorts: a first cohort of 121 COPD patients that already exists (currently closed to inclusions but still undergoing follow-up (NCT00404430)) and a new cohort of 150, decompensated or not, COPD patients.

This study is of major scientific interest and will enable to obtain extremely important information to better understand COPD.

Primary outcome measures

• Change of the pulse wave velocity (PWV) [Time frame: During 5 years since inclusion (once a year)]

Secondary outcome measures (5)

• Monitoring of COPD exacerbations compared to evolution of PWV [Time frame: During 5 years since inclusion]
• Relationship between the new cardiovascular (CV) events and the evolution of the PWV. [Time frame: During 5 years since inclusion (once a year)]
• Correlations between the parameters of severity of pulmonary disease and physical activity. [Time frame: During 5 years since inclusion (once a year)]
• Prevalence of nocturnal "non-dipping" of blood pressure during COPD. [Time frame: During 5 years since inclusion (once a year)]
• Impact of sleep disorders and sleep apnea syndrome on the evolution of CVR during COPD. [Time frame: At inclusion visit]

Eligibility criteria

Inclusion criteria

For patients with stable COPD:

• Men or women aged 18 to 85
• FEV1/FVC < 70% or proven BPCO
• Patients who have given their free and informed consent in writing

For patients with decompensated COPD:

• Men or women aged 18 to 85
• FEV1/FVC < 70% or proven BPCO
• At the time of acute respiratory failure (ARF), when admitted to hospital:

• Respiratory rate > 25 cycles per minute
• PaCO2 > 45 mmHg
• blood pH < 7.35
• When included in the study:

• pH > 7.33 at the end of ARF, 2 days in a row, or 3 to 7 days post-D1 decompensation (admission to the hospital)
• Fever < 38.5°C
• Patients who have given their free and informed consent in writing

Exclusion criteria

• Obvious evolving infection or CRP > 100 mg/L
• Cardiac decompensation considered the main cause of decompensation or chronic heart failure with LVEF < 45%
• Evolving neoplasia
• On antioxidants: N-acetyl-cysteine, selenium, vit. C, vit. E
• Pregnant or nursing women
• Patients under tutorship or curatorship
• Patients participating in a drug clinical research study
• Patients not affiliated to the French social security system (or equivalent)
• Patients deprived of liberty or hospitalized without consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• University Grenoble Hospital — Grenoble

Publications

• Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004 Jul;59(7):574-80. doi: 10.1136/thx.2003.019588. PMID 15223864
• Mallia P, Johnston SL. Mechanisms and experimental models of chronic obstructive pulmonary disease exacerbations. Proc Am Thorac Soc. 2005;2(4):361-6; discussion 371-2. doi: 10.1513/pats.200504-025SR. PMID 16267363
• de Torres JP, Cordoba-Lanus E, Lopez-Aguilar C, Muros de Fuentes M, Montejo de Garcini A, Aguirre-Jaime A, Celli BR, Casanova C. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J. 2006 May;27(5):902-7. doi: 10.1183/09031936.06.00109605. Epub 2006 Feb 2. PMID 16455829
• Malo O, Sauleda J, Busquets X, Miralles C, Agusti AG, Noguera A. [Systemic inflammation during exacerbations of chronic obstructive pulmonary disease]. Arch Bronconeumol. 2002 Apr;38(4):172-6. Spanish. PMID 11953269
• Dekhuijzen PN, Aben KK, Dekker I, Aarts LP, Wielders PL, van Herwaarden CL, Bast A. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):813-6. doi: 10.1164/ajrccm.154.3.8810624. PMID 8810624
• Rahman I. The role of oxidative stress in the pathogenesis of COPD: implications for therapy. Treat Respir Med. 2005;4(3):175-200. doi: 10.2165/00151829-200504030-00003. PMID 15987234
• Heunks LM, Vina J, van Herwaarden CL, Folgering HT, Gimeno A, Dekhuijzen PN. Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Physiol. 1999 Dec;277(6):R1697-704. doi: 10.1152/ajpregu.1999.277.6.R1697. PMID 10600916
• Yende S, Waterer GW, Tolley EA, Newman AB, Bauer DC, Taaffe DR, Jensen R, Crapo R, Rubin S, Nevitt M, Simonsick EM, Satterfield S, Harris T, Kritchevsky SB. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax. 2006 Jan;61(1):10-6. doi: 10.1136/thx.2004.034181. Epub 2005 Nov 11. PMID 16284220

Identifiers

NCT: NCT03014609 · 38RC16.245

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗