To the Editor—We read with great interest the study by Justice et al in which they build upon their prior work by incorporating inflammatory markers (sCD14 and D-dimer) into the Veterans Aging Cohort Study (VACS) index in order to improve its predictive accuracy for mortality [1, 2]. Cardiovascular disease (CVD) deaths are an important cause of mortality in human immunodeficiency virus (HIV)–infected patients, and thus it is notable that none of the components of the VACS index represent CVD risk factors. We therefore explored the use of the VACS index in assessing CVD burden using coronary artery calcium (CAC) scores, a validated surrogate marker of CVD events [3], as the response variable. Additionally, we assessed whether additional inflammatory molecules and endothelial dysfunction markers might modify this association. We utilized the Hawaii Aging with HIV–Cardiovascular Study cohort, a longitudinal study of the role of oxidative stress and inflammation in HIV cardiovascular risk.
Univariate logistic regression models were used to estimate odds ratios for the association between CAC scores (presence/absence) and VACS index and components of VACS index (Table 1). A significant association between the VACS index and presence of CAC was observed (P <.01). When the VACS was broken down to its components (age, current CD4 count, HIV RNA, hemoglobin, FIB-4, eGFR, and coinfection with hepatitis C), only age correlated with CAC scores. When both VACS index and age were included in the model, P values of the Wald test for age and VACS index were <.01 and .47, respectively, suggesting that age is relatively more important than the VACS index in association with the CAC score. Lastly, we assessed the association between the following inflammatory molecules and endothelial dysfunction markers and the VACS index: soluble adhesion molecules (sICAM-1, sVCAM-1), soluble E-selectin, plasminogen activator inhibitor 1, tumor necrosis factor α, monocyte chemotactic protein 1, and c-reactive protein. No association was found between these biomarkers and the VACS index.
Table 1.
Association of Veterans Aging Cohort Study Index and Its Components With Coronary Artery Calcium
| Variable | Odds Ratio | P Value | No. |
|---|---|---|---|
| VACS index | 1.05 | <.01 | 150 |
| Age | 1.15 | <.01 | 150 |
| Current CD4 | 1.00 | .76 | 150 |
| HIV RNA | 1.00 | .53 | 150 |
| Hemoglobin | 0.99 | .54 | 150 |
| FIB-4 | 1.00 | .76 | 118 |
| eGFR | 0.98 | .11 | 119 |
| Hepatitis C | 1.77 | .30 | 150 |
Abbreviations: HIV, human immunodeficiency virus; VACS, Veterans Aging Cohort Study.
This study is limited by its reliance on a surrogate marker of CVD rather than on clinical outcomes. Our cohort differs from the VACS cohort ethnically and by its composition predominantly of nonveterans. All our subjects were on stable antiretroviral therapy, and 85% of them had an undetectable HIV load. Despite these differences, our findings have important implications and suggestions for future research. Our data demonstrate that, although the VACS index correlates with CAC scores, a validated surrogate marker of CVD risk, this association is exclusively driven by age. Whether or not the other components of the VACS index are useful to predict CVD mortality as a subset of all-cause mortality is uncertain. In order to better refine the utility of the VACS index, it will be critical to assess its association with cause-specific mortality, including CVD mortality.
Notes
Financial support. This work was supported by the National Institute of Health (grants U54RR026136, U54MD007584, K23HL088981, and R01HL095135). D.C. and C.S. have received institutional funding from the National Heart, Lung, and Blood Institute, the National Institute on Minority Health and Health Disparities, and the National Center for Research Resources.
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
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