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/sec (SD 0.32). Eighteen participants (15.5%) had PASP of at least 40 mmHg, and 9 (7.8%) had TRV of at least 3.0 m/sec. Elevated TRV was significantly associated with CD4 cell counts below 200 cells/μl and higher log HIV RNA levels. Forced expiratory volume in one second (FEV1) percent predicted, FEV1/forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLco) percent 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 increased 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. Conclusions 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 COPD coexist in HIV and may arise secondary to common inflammatory mechanisms.

Enhanced Pulmonary Arteriopathy in Simian Immunodeficiency Virus–infected Macaques Exposed to Morphine

“…Morris and colleagues recently reported for the first time a link between echocardiographic manifestations related to pulmonary vascular disease and the inflammatory phenotype in HIV-infected individuals (49). Consistent with these observations, we also found significantly increased perivascular cell infiltrates around remodeled vessels in addition to a trend toward up-regulation of proinflammatory mediators such as MCP-1 and IL-8 in the VM group.…”

Heart–Lung Interaction via Infection

“…For example, in a cohort of HIV-infected outpatients, we found that pulmonary function is significantly associated with multiple aspects of cardiovascular disease, including coronary artery calcification and echocardiographic evidence of pulmonary hypertension (17; Morris, unpublished data). HIV-infected participants with elevated pulmonary artery pressures on echocardiography (defined as tricuspid regurgitant jet velocity [TRV] > 3.0 m/s) had significantly worse airflow (17). This relationship with abnormal lung function was similar with pulmonary artery systolic pressure (PASP).…”

“…An example of one such infection is HIV. Lung and cardiac diseases, including CVD and pulmonary hypertension, have been reported to be accelerated in individuals with HIV and seem to occur together (16)(17)(18)(19)(20). For example, in a cohort of HIV-infected outpatients, we found that pulmonary function is significantly associated with multiple aspects of cardiovascular disease, including coronary artery calcification and echocardiographic evidence of pulmonary hypertension (17; Morris, unpublished data).…”

“…In one study of HIV-infected individuals, lower DL CO was associated with greater sputum neutrophils in smokers and nonsmokers (23). We also examined the relationship of pulmonary artery pressure measurements to pulmonary and systemic inflammation in the cohort of HIV-infected individuals described above (17). Percent sputum neutrophils tended to increase with increasing TRV, and increasing sputum IL-8 was significantly associated with higher PASP and TRV.…”

Injection Drug Use as a “Second Hit” in the Pathogenesis of HIV-associated Pulmonary Hypertension

“…Injection Drug Use as a "Second Hit" in the Pathogenesis of HIV-associated Pulmonary Hypertension HIV-associated pulmonary arterial hypertension (HIV-PAH) is a serious complication that develops in approximately 1:200 of HIV-infected individuals, and an even higher prevalence of echocardiographic signs of pulmonary hypertension indicates that the disease may be more common than previously thought (1)(2)(3). Mortality is high, even in the era of antiretroviral therapy (ART) (4).…”