Declining Lung Function and Cardiovascular Risk: The ARIC Study

Abstract

Background: Pulmonary dysfunction predicts incident cardiovascular disease (CVD).

Objectives: The purpose of this study was to evaluate whether longitudinal decline in lung function is associated with incident heart failure (HF), coronary heart disease (CHD), and stroke.

Methods: Among 10,351 participants in the ARIC (Atherosclerosis Risk In Communities) study free of CVD, rapid lung function decline was defined as the greatest quartile (n = 2,585) of decline in either forced expiratory volume in 1 s (FEV₁) (>1.9% decline/year) or forced vital capacity (FVC) (>2.1% decline/year) over 2.9 ± 0.2 years. The relationship between rapid decline in FEV₁ or FVC and subsequent incident HF, CHD, stroke, or a composite of these was assessed using multivariable Cox regression adjusting for the baseline spirometry value, demographics, height, body mass index, heart rate, diabetes, hypertension, low-density lipoprotein, use of lipid-lowering medication, N-terminal fragment of prohormone for B-type natriuretic peptide, and smoking.

Results: The mean age was 54 ± 6 years, 56% were women, and 81% were white. At 17 ± 6 years of follow-up, HF occurred in 14%, CHD 11%, stroke 6%, and the composite in 24%. Rapid decline in FEV₁ and in FVC were both associated with a heightened risk of incident HF (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.33; p = 0.010; and HR: 1.27; 95% CI: 1.12 to 1.44; p < 0.001; respectively), with rapid decline in FEV₁ most prognostic in the first year of follow-up (HR: 4.22; 95% CI: 1.34 to 13.26; p = 0.01). Rapid decline in FEV₁ was also associated with incident stroke (HR: 1.25; 95% CI: 1.04 to 1.50; p = 0.015).

Conclusions: A rapid decline in lung function, assessed by serial spirometry, is associated with a higher incidence of subsequent CVD, particularly incident HF.

Keywords: FEV(1); FVC; cardiovascular disease; heart failure; lung function.

Figure 1. Association of rapid decline in FEV₁ with incident cardiovascular disease

Rapid decline is defined as greatest quartile of decline in FEV₁ over a mean of 2.9 years. Kaplan-Meier curves demonstrate the rates of (A) incident heart failure, (B) incident coronary heart disease, (C) incident stroke, and (D) the composite of these among the rapid decliner and non-rapid decliner groups. Hazard ratios (HR) and associated 95% confidence intervals are calculated from Cox regression models adjusted for age, sex, race, ARIC center, height, heart rate, body mass index, LDL-cholesterol, NT-proBNP, diabetes, hypertension, and smoking. For heart failure, a violation of the proportional hazards assumption was noted for this endpoint, indicated by the significant p for interaction for decline in percentage of predicted FEV₁ and time with respect to incident heart failure. The Panel A inset shows the Kaplan-Meier curve restricted to the 1^st year of follow-up. HRs are provided separately for pre-1 year and post-1year follow-up (indicated by dashed line), with associated P for interaction.

Figure 2. Association of rapid decline in FVC with incident cardiovascular disease

Rapid decline is defined as greatest quartile of decline in FVC over a mean of 2.9 years. Kaplan-Meier curves demonstrate the rates of (A) incident heart failure, (B) incident coronary heart disease, (C) incident stroke, and (D) the composite of these among the rapid decliner and non-rapid decliner groups. Hazard ratios (HR) and associated 95% confidence intervals are calculated from Cox regression models adjusted for age, sex, race, ARIC center, height, heart rate, body mass index, LDL-cholesterol, NT-proBNP, diabetes, hypertension, and smoking.

Central Illustration. Association of Rapid Decline in Lung Function With Subsequent Cardiovascular Disease

Rapid decline is defined as the greatest quartile of decline in either FEV₁ (Panel A) or FVC (Panel B) over a 2.9 year period. Kaplan-Meier curves demonstrate rates of subsequent cardiovascular disease (CVD) among the rapid decliner and non-rapid decliner groups. CVD is defined as a composite of heart failure, coronary disease, and stroke. Hazard ratios (HR) and associated 95% confidence intervals are calculated from Cox regression models adjusted for age, sex, race, ARIC center, height, heart rate, body mass index, LDL-cholesterol, NT-proBNP, diabetes, hypertension, and smoking.