We found that HIV-infected women have higher mean NT-pro-BNP than HIV-uninfected women. Similarly, markers of advanced HIV disease including CD4+
count below 200
cells/μl and ADI were associated with higher NT-pro-BNP, although multivariate analyses suggested that these associations were explained by comorbidities including anemia, HCV, and impaired kidney function, which were more prevalent in the HIV-infected group. Our findings suggest that NT-pro-BNP levels among HIV-infected patients are a global marker of non-HIV-related comorbidities known to be associated with higher natriuretic peptide levels.
Concern regarding CV disease in HIV-infected individuals has led to multiple studies examining the associations of HIV infection with atherosclerosis, left ventricular dysfunction, and congestive heart failure.26
Natriuretic peptides including NT-pro-BNP are markers of hemodynamic stress, and are used clinically to aid in the detection of LV dysfunction and the evaluation and management of congestive heart failure.27
Recently, however, the measurement of natriuretic peptides has been shown to provide prognostic information in patients with acute and chronic coronary artery disease.7,28
Accordingly, measurement of plasma BNP level has been suggested to be a cost-effective means of screening for CV disease.29,30
Few prior studies have assessed natriuretic peptide levels and cardiac function in HIV-infected populations12–15
and none hasspecifically examined NT-Pro-BNP levels. Carillo-Jimenez found serum levels inversely related to LV function in 10 HIV-infected patients assessed by echocardiography.12
In contrast, a Danish study of 95 HIV-infected patients found no correlation between NT-pro-BNP levels and LV or right ventricular ejection fraction measured by radionuclide ventriculography.13
That finding could be explained by unmeasured factors other than cardiac function contributing to elevated NT-pro-BNP levels. A prior German study performed cardiac magnetic resonance imaging on 12 HIV-infected subjects with elevated BNP levels and found multiple abnormalities including left ventricular hypertrophy, myocarditis, dilated cardiomyopathy, and right ventricular failure.15
These findings support the interpretation that natriuretic peptide levels are a global measure of CV disease.30
Our findings indicate that the prevalence of elevated NT-pro-BNP in HIV-infected individuals is almost twice that of HIV-uninfected individuals (12.1% vs. 7.5%, respectively, p
In our study, elevated NT-pro-BNP levels were significantly associated with HCV infection, anemia, and kidney dysfunction. These findings are consistent with prior studies showing higher natriuretic peptide levels associated with the same factors in HIV-uninfected populations.31
HCV has been previously reported to be associated with myocarditis, cardiomyopathy, and elevated NT-pro-BNP in HIV-uninfected populations.32,33
Among 1355 patients with heart failure, elevated NT-pro-BNP levels were found in 42 of 42 patients (100%) who had HCV antibodies.31
Though the exact mechanism of cardiac involvement in HCV infection is unclear, it is believed that HCV may promote the development of cardiomyopathy by inducing myocarditis, wherein an inflammatory response induces growth and cell death in cardiac cells.34
The strong relationship between NT-pro-BNP and advanced renal disease has also been reported in prior studies of HIV-uninfected individuals.35–37
Elevated NT-pro-BNP levels among patients with renal disease may reflect a chronic fluid overload state or may be related to other comorbidities that may increase LV wall tension.
We found that HIV infection was not associated with NT-pro-BNP after adjustment for comorbidities and other variables in the linear regression models. However, HIV is associated with an increased occurrence of myocarditis, cardiomyopathy, as well as atherosclerosis.1,7,38,39
It is also associated with comorbid conditions including anemia, renal insufficiency, and hepatitis, which were independently associated with elevated NT-pro-BNP. These findings suggest natriuretic peptide levels are nonspecific markers of general medical (non-HIV-specific) comorbidities in patients with HIV infection.
In the present study, there was a strong inverse relationship between obesity and plasma NT-pro-BNP levels. This finding is consistent with prior studies of natriuretic peptides in non-HIV-infected populations. Although the explanation for this finding is currently debated, higher testosterone levels and lower adiponectin levels seen in overweight and obese subjects have been implicated.40,41
Another interesting finding in this study was the J-shaped relationship between systolic BP and natural log-transformed NT-pro-BNP levels (). Although a J-shaped curve has been previously reported for BP and CV outcomes,42
natriuretic peptide levels are linearly related to CV outcomes.43
High systolic BP may directly increase LV workload and tension. Although the exact mechanism for the association between low systolic BP and higher NT-pro-BNP level is unclear, clinically stable hypotension is a frequent finding in advanced congestive cardiomyopathy.44
High LV wall stress or expanded plasma volume may contribute to higher NT-pro-BNP in such patients.
The J-shaped relationship between systolic blood pressure and naturally log-transformed NT-pro-BNP (log-NT-pro-BNP) among HIV-infected women, the Women's Interagency HIV Study (WIHS).
This is the largest study of NT-pro-BNP in HIV-infected individuals in the United States. However, this study has limitations, including a cross-sectional design that makes it difficult to attribute causality between the investigated factors and NT-pro-BNP levels. LV function and atherosclerosis are known to be associated with NT-pro-BNP; however, they were not investigated in this study. Finally, although the women in the WIHS reflect the demographics of the HIV epidemic among women in the United States, generalizability of our findings to HIV-infected men is limited as women have been found to have higher levels of natriuretic peptide. Moreover, women in this study had relatively well-controlled HIV infection, and had been enrolled in a prospective study for many years at the time of NT-pro-BNP assessment.
In summary, we found HIV-infected women had higher mean NT-pro-BNP levels compared to HIV-uninfected women. However, HIV infection was not associated with higher levels of NT-pro-BNP after controlling for relevant covariates. Among HIV-infected women, higher NT-pro-BNP levels were related to non-HIV-specific comorbidities including anemia, hepatitis C, and kidney disease. Increased life expectancy of HIV-infected individuals has led to the need for new biomarkers of comorbidities in this population. Longitudinal research is needed to determine the prognostic value of high natriuretic peptide levels in HIV-infected individuals for cardiac and noncardiac clinical endpoints.