Albuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study

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 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV/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.