Association of lung diffusion capacity with cardiac remodeling and risk of heart failure: The Framingham heart study

Abstract

Background: Lung function abnormalities are ubiquitous in heart failure (HF). It is unclear, however, if abnormal lung diffusion capacity is associated with cardiac remodeling and antedates HF. We hypothesized that lower lung diffusion capacity for carbon monoxide (DLCO) is associated with worse left ventricular (LV) systolic and diastolic function cross-sectionally, and with higher risk of HF prospectively.

Methods: We evaluated 2423 Framingham Study participants (mean age 66 years, 55% women) free of HF who underwent routine echocardiography and pulmonary function tests. We used multivariable regression models to relate DLCO, forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) to left ventricular ejection fraction (LVEF), left atrial (LA) emptying fraction (LAEF), E/e', E/A, LV mass, and LA diameter (LAD). Multivariable-adjusted Cox proportional hazards regression was used to relate DLCO, FEV1, and FVC to incident HF.

Results: In multivariable-adjusted cross-sectional analyses, DLCO, FEV1, and FVC (dependent variables) were associated positively with LVEF (βDLCO = 0.208, βFEV1 = 0.021, and βFVC = 0.025 per 5% increment in LVEF; p<0.005 for all), and LAEF (βDLCO = 0.707, βFEV1 = 0.058 and βFVC = 0.058 per 5% increment in LAEF; p<0.002 for all). DLCO and FVC were inversely related to E/A (βDLCO = -0.289, βFVC = -0.047 per SD increment in E/A; p<0.001 for all). Additionally, DLCO, FEV1 and FVC were inversely related to HF risk (108 events, median follow-up 9.7 years; multivariable-adjusted hazard ratios per SD increment 0.90, 95% CI 0.86-0.95; 0.42, 95% CI 0.28-0.65, and 0.51, 95% CI 0.36-0.73, respectively). These results remained robust in analyses restricted to non-smokers.

Conclusions: Our large community-based observations are consistent with the concept that lower lung diffusion capacity and expiratory flow rates are associated with cardiac remodeling and may antedate HF. Additional studies are needed to confirm our findings and to evaluate the prognostic utility of pulmonary function testing for predicting HF.

Fig 1. Kaplan-Meier curves depicting the association between tertiles of DLCO and risk of HF (green represents the highest, blue is the middle, and red is the lowest tertile).

Fig 2. Kaplan-Meier curves depicting the association between tertiles of FEV1 and risk of HF (green represents the highest, blue is the middle, and red is the lowest tertile).

Fig 3. Kaplan-Meier curves depicting the association between tertiles of FVC and risk of HF (green represents the highest, blue is the middle, and red is the lowest tertile).

Fig 4. Multivariable adjusted RCS splines assessing for potential nonlinearity of the associations of DLCO, FEV1, and FVC with incidence of HF.