1. Update on the VACS HIV CVD Substudy and Preliminary Analyses
Matthew S. Freiberg, MD, MSc
University of Pittsburgh
April 8, 2010

2. Specific Aims
(1) Evaluate whether HIV is an independent risk factor for cardiovascular disease (CVD) and whether HIV viral load; CD4 counts; duration, type, and adherence to combination antiretroviral therapy (CART); HCV and substance use increase CVD risk
(2) Evaluate the cross-sectional association of HIV infection and CART and
(3) Hepatitis C and substance use with potential mechanisms of CVD among HIV infected and uninfected persons.

3. VACS Conceptual Model for Alcohol, HIV and CVD
Freiberg et al. Alcohol Research and Health 2010

5. Self-reported CVD events within and outside the VA Health Care system
Cardiovascular Disease Events among 1496 surveyed VACS Participants
Site
VA Events
Non-VA Events
Atlanta 38 13
Bronx 34 7
Houston 32 6
Los Angeles 14 18
New York 4 2
Baltimore
Washington, D.C. 39 24
Pittsburgh 1
Total
172 
75 
There are a total of 247 cardiovascular events.

6. MI/CHD events within VA by screening criteria
VA screening process for MI/CHD:
-1601 participants who have a diagnostic ICD-9 codes
-148 participants had procedure ICD-9 codes (e.g., PTCA, CABG)
-881 participants have met pharmacy criteria (e.g., nitroglycerine)
-3345 participants have laboratory criteria (e.g., CPK or Troponin values)

7. Sample of Online Web Adjudication Site

8. Mechanistic Studies The 600 Substudy participants
Exercise treadmill test
Complete echocardiogram study
CT scan (measuring 10 endpoints)
Coronary artery, aortic valve, and mitral value annular calcium
Left ventricular size and thoracic aorta calcium
Liver : spleen fat ratio
Abdominal visceral and subcutaneous fat, epicardial fat, and thigh fat
Laboratory testing (serum biomarkers)
Endothelial function: (eg., sICAM-1)
Thrombosis: (e.g., D-dimer)
Other: (e.g., IL-6)

9. Mechanistic Substudy Current Enrollment and Completed Testing
Site
Current
Enrollment
and
Target
Completed Testing
Blood
GXT/6MW
Echo
CT scan
Baltimore
24 / 275 10
13 / 0 12 2 LA
17 / 275
7 / 0 7
Pittsburgh
5 / 50
3 / 3 3
Total
46 / 600 22
23 / 3 5

10. Ischemic Heart Disease Quality Enhancement Research Initiative (IHD QUERI)
The overall mission of the IHD QUERI is to improve the quality of care and health outcomes of veterans with IHD
To this end, all myocardial infarctions occurring within the VA from 2003 to 2008 were chart reviewed using standardized protocols

11. QUERI and Virtual Cohort Merger
Virtual Cohort and IHD QUERI merger
Virtual Cohort (40594 HIV+, HIV-)
Acute Myocardial Infarctions ( )
993 total events
379 events among HIV infected veterans
614 events among HIV uninfected veterans
These numbers do NOT include PTCA, stent, or CABG performed without
preceding AMI nor do these account for events outside VA system

12. Preliminary Data

13. Acknowledgements PI and Co-PI: AC Justice, DA Fiellin
Scientific Officer (NIAAA): K Bryant
Participating VA Medical Centers: Atlanta (D. Rimland), Baltimore (KA Oursler, R Titanji), Bronx (S Brown, S Garrison), Houston (M Rodriguez-Barradas, N Masozera), Los Angeles (M Goetz, D Leaf), Manhattan-Brooklyn (M Simberkoff, D Blumenthal, H Leaf, J Leung), Pittsburgh (A Butt, E Hoffman), and Washington DC (C Gibert, R Peck)
Core Faculty: K Mattocks (Deputy Director), K Akgun, S Braithwaite, C Brandt, K Bryant, R Cook, K Crothers, J Chang, S Crystal, N Day, R Dubrow, M Duggal, J Erdos, M Freiberg, M Gaziano, M Gerschenson, A Gordon, J Goulet, N Kim, M Kozal, K Kraemer, V LoRe, S Maisto, P Miller, P O’Connor, C Parikh, C Rinaldo, J Samet
Staff: H Bathulapalli, T Bohan, D Cohen, A Consorte, P Cunningham, A Dinh, C Frank, K Gordon, J Huston, F Kidwai, F Levin, K McGinnis, C Rogina, J Rogers, L Sacchetti, M Skanderson, J Tate, E Williams
Major Collaborators: VA Public Health Strategic Healthcare Group, VA Pharmacy Benefits Management, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Yale Center for Interdisciplinary Research on AIDS (CIRA), Center for Health Equity Research and Promotion (CHERP), ART-CC, NA-ACCORD, HIV-Causal
Major Funding by: National Institutes of Health: NIAAA (U10-AA13566), NIA (R01-AG029154), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347) , NIAID (U01-A ), NIMH (P30-MH062294), and the Veterans Health Administration Office of Research and Development (VA REA ) and Office of Academic Affiliations (Medical Informatics Fellowship).

14. Acknowledgements Investigator Amy Justice, MD, PhD Co-Investigators
John Gottdiener, MD
Dan Edmundowicz, MD
Adeel Butt, MD, MS
Sheldon Brown, MD
Joyce Chang, PhD
Matthew Budoff, MD
Matthew Goetz, MD
Cynthia Gilbert, MD
David Leaf, MD MPH
Maria Rodriguez-Barradas, MD
Kris Ann Oursler MD, ScM
Stephen Gottlieb, MD
Lewis Kuller, MD, DrPH
Insert title
Elliot Lowy
Melissa Skanderson
Kathleen McGinnis
Elizabeth Sorek
Sean Wang
Carol Rogina
Travis Rabbit
Kaku Armah
Courtney Watson

15. Acknowledgements

16. Studies and Results Testing Protocols for 600 person substudy
Echo: ready to start
CT: ready to start except one “dummy scan” from LA VA
GXT: ready to start
Lab protocol: finalizing bar coding procedure and final run through with technician from Russ Tracy’s laboratory
Enrollment projected for first week of October 2009

17. Studies and Results

18. Studies and Results
Currently enrolling all VACS participants (3227 HIV+, 2340HIV-)
Survey items quantifying family history of CVD and self-reported CVD events within and outside the VA hospital system
Laboratory measurements being collected
Hepatitis C antibody and viral RNA levels
Fasting lipid panel and glucose testing
Physical Measurements being collected
Blood pressure
Height and weight

19. Studies and Results On-line Web adjudication system
Adjudication process started
Virtual Cohort (41,630 HIV+, HIV-)
Acute Myocardial Infarctions ( )
1021 total events (41% HIV infected)
VACS cohort
90 total events (45% HIV infected)
These numbers do NOT include PTCA, stent, or CABG performed without
preceding AMI nor do these account for events outside VA system
Data based on Quality Enhancement Research Initiative (QUERI) IHD

20. Cardiovascular Disease Mechanisms in HIV Infected and Uninfected Veterans
Matthew S. Freiberg, MD, MSc
University of Pittsburgh
Veterans Aging Cohort Study Meeting
New Haven, Connecticut
October 14th, 2008

21. Data Collection: Mechanistic Studies Aim 2 and Aim 3
The 600 Substudy participants
Exercise treadmill test
Complete echocardiogram study
CT scan (measuring 10 endpoints)
Coronary artery, aortic valve, and mitral value annular calcium
Left ventricular size and thoracic aorta calcium
Liver : spleen fat ratio
Abdominal visceral and subcutaneous fat, epicardial fat, and thigh fat
Laboratory testing (serum biomarkers)
Endothelial function: sICAM-1, serum tissue factor, factor VIIIc
and von Willebrand Factor
Thrombosis: D-dimer, plasminogen, t-PA antigen, PAI-1, TPA/PAI-1 complex, TAF1, thrombin-antithrombin complex (TAT)
Other: Lp (a), hs CRP, IL-6, SSA, Cystatin C, Fibrinogen, and insulin

22. Data Collection: Prospective Studies Aim 1
Traditional and Non-traditional CVD risk factors in VACS
Blood pressure measurement, height, and weight*
Fasting lipid panel and glucose*
Hepatitis C testing and quantification (HCV antibody and viral load)
Information on family history of CVD
Information on CVD events outside of the VA system
Adjudicate CVD outcomes in VACS
Coronary Heart Disease (CHD): Myocardial Infarction and coronary revascularization
Non-CHD CVD: stroke, peripheral vascular disease, congestive heart failure, deep venous thrombosis, and pulmonary embolism
Will include both prevalent and incident events
* Will not be obtained at the Atlanta site due to logistic constraints