Cardiopulmonary function in individuals with HIV infection in the antiretroviral therapy era

Abstract

Objective: To determine relationship of echocardiographic measures of pulmonary hypertension to lung function and inflammatory biomarkers in HIV-infected individuals.

Design: Cross-sectional study of 116 HIV-infected outpatients.

Methods: Doppler-echocardiography and pulmonary function testing were performed. Induced sputum and plasma cytokines, sputum cell counts and differentials, markers of peripheral T-cell activation, and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Univariate and multivariate analyses determined relationship of echocardiographic variables to pulmonary function, inflammation, and NT-proBNP.

Results: Mean estimated pulmonary artery systolic pressure (PASP) was 34.3 mmHg (SD 6.9) and mean tricuspid regurgitant jet velocity (TRV) was 2.5 m/s (SD 0.32). Eighteen participants (15.5%) had PASP of at least 40 mmHg, and nine (7.8%) had TRV of at least 3.0 m/s. Elevated TRV was significantly associated with CD4 cell counts below 200 cells/μl and higher log HIV-RNA levels. Forced expiratory volume in 1 s (FEV(1)) percentage predicted, FEV(1)/forced vital capacity, and diffusing capacity for carbon monoxide (DLco) percentage predicted were significantly lower in those with elevated PASP or TRV. Sputum interleukin-8, peripheral interleukin-8, peripheral interferon-γ levels, and CD8(+) T-cell expression of CD69(+) were associated with increasing PASP and TRV. Log NT-proBNP was significantly higher with increasing PASP and TRV. Left ventricular function was not associated with PASP or TRV.

Conclusion: Echocardiographic manifestations of pulmonary hypertension are common in HIV and are associated with respiratory symptoms, more advanced HIV disease, airway obstruction, abnormal DLco, and systemic and pulmonary inflammation. Pulmonary hypertension and chronic obstructive pulmonary disease coexist in HIV and may arise secondary to common inflammatory mechanisms.

Figure 1

Percentage of participants reporting respiratory symptoms compared by A. Normal or elevated pulmonary artery systolic pressures (≥40 mm Hg) and B. Normal or elevated tricuspid regurgitant velocity (≥3.0 m/sec). Abbreviations: PASP, pulmonary artery systolic pressure; TRV, tricuspid regurgitant velocity

Figure 2

Comparison of pulmonary function values for HIV-infected individuals with A. Normal or elevated pulmonary artery systolic pressures (≥40 mm Hg) and B. Normal or elevated tricuspid regurgitant velocity (≥3.0 m/sec) showing significantly worse pulmonary function in those with elevated echocardiographic pressures. Abbreviations: PASP, pulmonary artery systolic pressure; TRV, tricuspid regurgitant velocity

Figure 3

Relationship of peripheral cytokines to PASP and TRV. Abbreviations: IL, interleukin; IFN, interferon; PASP, pulmonary artery systolic pressure; TRV, tricuspid regurgitant velocity.