Controlled Exposures to Air Pollution in Patients With Coronary Heart Disease

NCT ID: NCT00437138

Last Updated: 2007-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2006-06-30

Brief Summary

Air pollution is a major cause of cardiovascular morbidity and mortality. The components of air pollution responsible and the mechanisms through which they might mediate these harmful effects remain only partially understood. We hypothesise that these adverse effects are mediated by combustion derived air pollutants and that even a brief exposure will effect heart and blood vessel function. We assess the effect of dilute diesel exhaust inhalation at levels encountered in urban road traffic on heart and blood vessel function in patients with stable coronary heart disease.

Detailed Description

Observational studies suggest that exposure to air pollution may worsen symptoms of angina and trigger acute myocardial infarction. These findings are limited by imprecision in the measurement of pollution exposure, the effect of potential confounding environmental and social factors, and the lack of mechanistic data. Controlled exposures of air pollutants can help to address these shortcomings by providing a precisely defined exposure in a regulated environment that facilitates investigation with validated biomarkers and surrogate measures of cardiovascular health. Using a carefully characterised exposure system, we have previously shown in healthy volunteers that exposure to dilute diesel exhaust causes lung inflammation, depletion of airway antioxidant defences, and impairment of vascular and fibrinolytic function. To date, there have been no controlled exposures in patients with coronary heart disease: an important population who may be particularly susceptible to the adverse cardiovascular effects of air pollution.

In a double blind randomized cross-over study, 20 patients with prior myocardial infarction will be exposed to dilute diesel exhaust (300µg/m3) or filtered air during periods of rest and moderate exercise in a controlled exposure facility. During the exposure, myocardial ischemia will be quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours following exposure, vascular vasomotor and fibrinolytic function will be assessed by means of intra-arterial agonist infusions.

Conditions

Coronary Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

Exposure to dilute diesel exhaust (300µg/m3) or filtered air

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Previous myocardial infarction (>6 months previously) treated by primary angioplasty and stenting
• On standard secondary preventative therapy

Exclusion Criteria

• Angina pectoris (Canadian Cardiovascular Society grade ≥2)
• History of arrhythmia
• Diabetes mellitus
• Uncontrolled hypertension
• Renal or hepatic failure
• Unstable coronary disease (acute coronary syndrome or unstable symptoms within 3 months)
• Occupational exposure to air pollution
• Current smokers
• Asthma
• Inter-current illness

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Umeå University

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Principal Investigators

David E Newby, MD

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Thomas Sandstrom, MD

Role: PRINCIPAL_INVESTIGATOR

Umeå University

Locations

Umeå University

Umeå, Västerbotten County, Sweden

Countries

Sweden

References

Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundback M, Cassee FR, Donaldson K, Sandstrom T, Blomberg A, Newby DE, Mills NL. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect. 2014 Jul;122(7):747-53. doi: 10.1289/ehp.1307337. Epub 2014 Mar 25.

Reference Type: DERIVED

PMID: 24667535 (View on PubMed)

Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD, Soderberg S, Boon NA, Donaldson K, Sandstrom T, Blomberg A, Newby DE. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007 Sep 13;357(11):1075-82. doi: 10.1056/NEJMoa066314.

Reference Type: DERIVED

PMID: 17855668 (View on PubMed)

Related Links

http://www.cvs.med.ed.ac.uk/

Centre for Cardiovascular Science, Edinburgh

http://www.bhf.org.uk/

British Heart Foundation

Other Identifiers

RG/05/003 DISARM 2

Identifier Type: -

Identifier Source: org_study_id