Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study

Megha A Parikh; Carrie P Aaron; Eric A Hoffman; Joseph E Schwartz; Jaime Madrigano; John H M Austin; Ravi Kalhan; Gina Lovasi; Karol Watson; Karen Hinckley Stukovsky; R Graham Barr

doi:10.1513/AnnalsATS.201604-317OC

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Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study

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Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study

Megha A Parikh, Carrie P Aaron, Eric A Hoffman, Joseph E Schwartz, Jaime Madrigano, John H M Austin, Ravi Kalhan, Gina Lovasi, Karol Watson, Karen Hinckley Stukovsky, …

Annals of the American Thoracic Society, Vol.14(5), pp.649-658

05/2017

DOI: 10.1513/AnnalsATS.201604-317OC

PMCID: PMC5427735

PMID: 28207279

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Abstract

Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45-84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than -950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.

United States

Smoking - adverse effects

Spirometry

Humans

Middle Aged

Male

Pulmonary Emphysema - drug therapy

Tomography, X-Ray Computed

Pulmonary Disease, Chronic Obstructive - physiopathology

Pulmonary Disease, Chronic Obstructive - complications

Pulmonary Emphysema - diagnostic imaging

Angiotensin-Converting Enzyme Inhibitors - administration & dosage

Regression Analysis

Aged, 80 and over

Female

Aged

Respiratory Function Tests

Longitudinal Studies

Angiotensin Receptor Antagonists - administration & dosage

Details

Title: Subtitle: Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study
Creators: Megha A Parikh - 1 Department of Medicine, College of Physicians and Surgeons
Carrie P Aaron - 1 Department of Medicine, College of Physicians and Surgeons
Eric A Hoffman - 2 Department of Radiology, University of Iowa, Iowa City, Iowa
Joseph E Schwartz - 3 Department of Psychiatry, Stony Brook University, Stony Brook, New York
Jaime Madrigano - 4 Department of Environmental Health Sciences, Mailman School of Public Health
John H M Austin - 5 Department of Radiology, College of Physicians and Surgeons, and
Ravi Kalhan - 6 Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
Gina Lovasi - 7 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
Karol Watson - 8 Division of Cardiology, School of Medicine, University of California, Los Angeles, Los Angeles, California; and
Karen Hinckley Stukovsky - 9 Department of Biostatistics, University of Washington, Seattle, Washington
R Graham Barr - 7 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
Resource Type: Journal article
Publication Details: Annals of the American Thoracic Society, Vol.14(5), pp.649-658
DOI: 10.1513/AnnalsATS.201604-317OC
PMID: 28207279
PMCID: PMC5427735
NLM abbreviation: Ann Am Thorac Soc
ISSN: 2325-6621
eISSN: 2325-6621
Publisher: American Thoracic Society; United States
Grant note: P30 ES005605 / NIEHS NIH HHS N01HC95169 / NHLBI NIH HHS UL1 RR025005 / NCRR NIH HHS R01 HL093081 / NHLBI NIH HHS N01HC95164 / NHLBI NIH HHS N01HC95160 / NHLBI NIH HHS R01 HL121270 / NHLBI NIH HHS R01 HL112986 / NHLBI NIH HHS RC1 HL100543 / NHLBI NIH HHS N01HC95159 / NHLBI NIH HHS UL1 RR024156 / NCRR NIH HHS R01 HL077612 / NHLBI NIH HHS R01 HL122477 / NHLBI NIH HHS N01HC95162 / NHLBI NIH HHS
Language: English
Date published: 05/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051782502771

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