Background: After accounting for established risk factors, people living with HIV (PLWHIV) have a 50-75% greater risk of acute myocardial infarction (AMI) than uninfected individuals. Several underlying causes for this association have been suggested including ongoing chronic inflammation, immune suppression, and a greater burden of anemia, renal disease, liver disease, and hepatitis C infection. While many of these factors have been studied in a cross-sectional manner, few have considered the association of cumulative HIV care measures with AMI among PLWHIV. We hypothesized that measuring these factors in a cumulative way would be associated with AMI incidence.
Methods: Retrospective cohort study including PLWHIV starting antiretroviral therapy (ART) in the Veterans Aging Cohort Study Virtual Cohort (VACS VC) from 2000-2009. The impact of baseline, time-updated and cumulative measures of HIV viremia, CD4 count and the VACS Index were modeled. Cumulative measures were captured starting 6 months after ART initiation until AMI event, death, last clinic visit or censor date (December 31, 2009) and calculated as follows:
1) Copy Years viremia (CYV)= Area under the curve of HIV viral load (VL) measures.
2) CD4 Years (CD4Y)= Area under the curve of CD4 measures.
3) VACS Index years (VISY)= Area under the VACS Index curve.
Areas under the curve were calculated using the trapezoidal rule. The VACS Index score was calculated using age, HIV-1 RNA, CD4, aspartate and alanine transaminases, hemoglobin, platelet count, creatinine and known hepatitis C infection. An online calculator is available (http://vacs.med.yale.edu). The primary outcome was incident AMI determined using Medicare and VA ICD9 codes. Multi-variable proportional hazard (PH) models were fit for time to AMI.
Results: 12,131 patients were included in the analysis. Separate PH models were fit for different measures of VL, CD4 and the VACS Index (basal, time-updated and cumulative) and results are presented in table 1. While all three cumulative measures predicted the studied outcome, VCY≥63, 000 copy-years/mL (HR=4.17; 95%CI=3.59-4.85) and CD4Y<750 cell-years/mm3 (HR=5.61; 95%CI=4.56-6.90); patients with higher VACS Index score-years had the highest risk of AMI (VISY≥250; HR=40.56; 95%CI=33.25-49.47).
Conclusions: Cumulative measures of viral load, CD4 count and VACS Index provide added information about risk of AMI, of these, VACS Index is the most comprehensive.
Table 1. Multivariable Cox Proportional Hazards analyses of factors associated with time to Acute Myocardial Infarction among patients starting Initial ART regimens in the VACS Virtual Cohort; 2000-2009.