NHLBI Working Group

Cardiovascular Disease in COPD: Evidences from Epidemiology, Genetics, Bio-Markers, Animal Models, Clinical Studies & Pharmacological treatments

Executive Summary

The National Heart, Lung, and Blood Institute convened a meeting of investigators on September 21-22, 2006, in Bethesda, Maryland, to evaluate evidence for a pathogenetic link between COPD (Chronic Obstructive Pulmonary Disease) and cardiovascular disease and to recommend future research that may be needed to clarify this relationship and to translate this understanding into better approaches for the prevention and treatment of cardiopulmonary disease.

Experts in cardiovascular disease and COPD were brought together for this working group. It was acknowledged that cardiovascular disease plays a major role in COPD, being responsible for the death of more than 30% of these patients. The need to look at COPD subjects as a whole in terms of the development, progression and treatment of a systemic disease was stressed. The general consensus was that the mechanisms behind the association of cardiovascular disease and COPD need to be further investigated at the epidemiological, patho-biological, and clinical levels. Therapeutic issues, with either beneficial or detrimental connotations, need to be clarified.

Several recommendations on priorities for future research directions were generated.

The general recommendations of the Working Group were:

• Analyses of existing data and new population-based epidemiological data are needed to clarify the relationship between cardiovascular disease and COPD, including the cardiovascular association with pulmonary function measures (e.g., FEV1) in those without clinically significant lung disease.
• Clinical studies are needed to determine the prevalence, pathogenesis, and consequences of thromboembolic abnormalities in subjects with chronic airflow limitation, including patients with stable COPD and during exacerbations.
• Basic research is needed to identify common pathobiological mechanisms that may contribute to vascular dysfunction in both pulmonary and systemic vessels of smokers with and without COPD.
• Studies are needed to assess the common mechanisms by which immune responses and inflammation may contribute to cardiovascular disease and COPD.
• The role of aging in the development of COPD and associated co-morbidities should be investigated.
• Critical examination of existing data is needed to clarify the safety profile of common cardiopulmonary drugs in patients with both conditions.
• Randomized controlled trials are needed to establish a pulmonary benefit of cardio-protective drugs such as angiotensin receptor antagonists and statins.
• Large cardiovascular and COPD trials of agents that might plausibly affect both conditions and that include co-morbid subjects should routinely include both cardiac and pulmonary endpoints (such as cardiac events and COPD exacerbation rate) as outcome variables.

Working Group Members

Chair

• Garret A. FitzGerald, M.D., University of Pennsylvania
• Stephen I. Rennard, M.D., Nebraska Medical Center

Members

• William C. Bailey, M.D., University of Alabama at Birmingham
• R. Graham Barr, M.D., Columbia University
• William A. Boisvert, M.D., Brigham & Women's Hospital
• Cynthia M. Boyd, M.D., Johns Hopkins University
• Joseph A. Caprini, M.D., Northwestern University
• Ronald G. Crystal, M.D., Weill Cornell Medical College
• Steve N. Georas, M.D., University of Rochester Medical Center
• Peter K. MacCallum, M.D., Barts and the London Queen Mary’s School of Medicine and Dentistry
• G.B. John Mancini, M.D., University of British Columbia and Vancouver Hospital and Health Sciences Centre
• Fernando J. Martinez, M.D., University of Michigan
• George O'Connor, M.D., Boston University School of Medicine
• Stephen Sidney, M.D., Kaiser Permanente Medical Care Program
• Don D. Sin, M.D., University of British Columbia
• Byron Thomashow, M.D., Columbia University
• Rubin Tuder, M.D., Johns Hopkins University
• Norbert Voelkel, M.D., University of Colorado Health Sciences Center

NHLBI Staff

• Thomas Croxton, Ph.D., M.D., Division of Lung Diseases
• Antonello Punturieri, M.D., Ph.D. Division of Lung Diseases
• Gail Weinmann, M.D., Division of Lung Diseases

November 2006