Albuminuria, lung function decline, and risk of incident chronic obstructive pulmonary disease the NHLBI pooled cohorts study

Elizabeth C. Oelsner, Pallavi P. Balte, Morgan E. Grams, Patricia A. Cassano, David R. Jacobs, R. Graham Barr, Kristin M. Burkart, Ravi Kalhan, Richard Kronmal, Laura R. Loehr, George T. O’Connor, Joseph E. Schwartz, Michael Shlipak, Russell P. Tracy, Michael Y. Tsai, Wendy White, Sachin Yende

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Rationale: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD. Objectives: To test whether albuminuria was associated with lung function decline and incident CLRDs. Methods: Six U.S. population–based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications. Measurements and Main Results: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV 1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV 1 decline (95% confidence interval [CI], 0.86–4.76%; P = 0.0047), 11.02% greater FEV 1 /FVC decline (95% CI, 4.43–17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2–31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18–34%, P, 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease. Conclusions: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population–based sample.

Original languageEnglish (US)
Pages (from-to)321-332
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Issue number3
StatePublished - Feb 1 2019

Bibliographical note

Funding Information:
Supported as follows: NHLBI Pooled Cohorts Study: NIH/NHLBI R21-HL121457, R21-HL-129924, K23-HL-130627. ARIC (Atherosclerosis Risk in Communities) Study: The ARIC study has been funded in whole or in part with Federal funds from the NHLBI, NIH, Department of Health and Human Services, under contract HHSN268201700001I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I, HHSN2682017000021. CARDIA (Coronary Artery Risk Development in Young Adults) Study: CARDIA is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), the University of Minnesota (HHSN268201300028C), the Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intraagency agreement between NIA and NHLBI (AG0005), as well as an NHLBI grant (to R.K.) R01 HL122477. This manuscript has been reviewed by CARDIA for scientific content. CHS (Cardiovascular Health Study): This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grants U01HL080295 and U01HL130114 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the NIA. A full list of principal CHS investigators and institutions can be found at FHS (Framingham Heart Study): From the Framingham Heart Study of the NHLBI of the NIH and Boston University School of Medicine. This work was supported by the NHLBI’s Framingham Heart Study (contract no. N01-HC-25195; HHSN268201500001I). Health ABC (Health Aging and Body Composition) Study: This research was supported by NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050; and by National Institute of Nursing Research grant R01-NR012459. MESA (Multi-Ethnic Study of Atherosclerosis): NIH/NHLBI R01-HL-077612, R01-HL-093081, RC1-HL-100543, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169. This publication was also developed under a STAR research assistance agreement, no. RD831697 (MESA Air), awarded by the U.S Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication.

Publisher Copyright:
Copyright © 2019 by the American Thoracic Society


  • Asthma
  • Epidemiology
  • Spirometry

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