1 / 62

HIV infection and cardiovascular diseases Matthew S. Freiberg, MD, MSc

HIV infection and cardiovascular diseases Matthew S. Freiberg, MD, MSc. University of Pittsburgh School of Medicine and Graduate School of Public Health Yale GIM Research in Progress September 8 th , 2011. This Grand Rounds is accredited for CME by the Yale School of Medicine.

gittel
Download Presentation

HIV infection and cardiovascular diseases Matthew S. Freiberg, MD, MSc

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. HIV infection and cardiovascular diseases Matthew S. Freiberg, MD, MSc University of Pittsburgh School of Medicine and Graduate School of Public Health Yale GIM Research in Progress September 8th, 2011

  2. This Grand Rounds is accredited for CME by the Yale School of Medicine. • If you wish to receive credit for your participation, • you must: • sign in DISCLOSURE & ACCREDITATION

  3. DISCLOSURE & ACCREDITATION Acknowledgement is made on behalf of the Department that: ~ There is no commercial support for this Grand Rounds. Confirmation is also made that today’s lecture and faculty disclosure have been peer reviewed and: ~There are no conflicts of interest.

  4. By 2015, what percentage of HIV infected people living in the U.S. will be 50 years of age or older • 15% • 25% • 35% • 50% http://www.cdc.gov/hiv/resources/factsheets/

  5. By 2015, what percentage of HIV infected people living in the U.S. will be 50 years of age or older • 15% • 25% • 35% • 50% http://www.cdc.gov/hiv/resources/factsheets/

  6. At the end of 2006, African Americans accounted for what percentage of all new HIV infection diagnoses • 15% • 35% • 45% • 50% http://www.cdc.gov/hiv/topics/aa/

  7. At the end of 2006, African Americans accounted for what percentage of all new HIV infection diagnoses • 15% • 35% • 45% • 50% http://www.cdc.gov/hiv/topics/aa/

  8. In 2006, the rate of new HIV infection for black women was nearly __ times as high as that of white women and nearly __ times that of Hispanic/Latina women. • 3 and 2 • 5 and 3 • 10 and 3 • 15 and 4 http://www.cdc.gov/hiv/topics/aa/

  9. In 2006, the rate of new HIV infection for black women was nearly __ times as high as that of white women and nearly __ times that of Hispanic/Latina women. • 3 and 2 • 5 and 3 • 10 and 3 • 15 and 4 http://www.cdc.gov/hiv/topics/aa/

  10. Background HIV infection is associated with Increased coronary calcium1 Progression of carotid IMT2 Endothelial dysfunction as measured by FMD3 Antiretroviral therapy (ARV) is associated with AMI risk in observational studies4 Intermittent ARV, however, is associated with a greater risk of AMI than continuous ARV for viral suppression5 1. Lai et al. Archives of Internal Medicine 2005; 2. Hsue et al. Circulation 2004; 3. Solages et al. CID 2006; 4. DAD study group. NEJM 2007; 5. SMART study group. NEJM 2006.

  11. The SMART Study The Strategies for Management of ART (SMART) study is a RCT of 5472 HIV+ Participants who were assigned either to drug Conservation or viral suppression Participants were followed for 16 months Primary end points was opportunistic disease or death from any cause (n=167) Secondary endpoints were major CVD, renal, or hepatic disease (n=104 of which 79 were CVD)

  12. The SMART Study The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. N Engl J Med 2006;355:2283-2296

  13. Important Questions Is HIV infection an independent risk factor for AMI? Does HIV infection increase the risk of other cardiovascular diseases? If HIV does increase the risk of CVD what is the mechanism? Do ARVs play a role? Do non-traditional risk factors play a role? If so, does the Framingham risk score apply to those with HIV infection?

  14. Is HIV as an independent risk factor for AMI

  15. Prior studies suggesting HIV is associated with a significant AMI risk • Triant et al.1 • AMI rate ratio=1.75 (95% CI=1.51-2.02, p<0.001) • Klein et al.2 • AMI rate ratio=1.4 (95% CI=1.3-1.7, p<0.001) • Obel et al.3 • IHD hospitalization RR=2.12 (95% CI=1.62-2.76) • Currier et al.4 • CHD RR=2.16 (95% CI=1.81-2.58) for men 25-34 • CHD RR=1.53 (95% CI=1.10-2.13) for women 25-34 1. Triant et al. J Clin Endo Metab 2007; 2. Klein et al. CROI. Boston, 2011; 3. Odell et al. CID. 2007 4. Currier et al. JAIDS 2003

  16. Veterans Aging Cohort Study Virtual Cohort and Ischemic Heart Disease Quality Enhance Research Initiative • Cohort of HIV+ and 1:2 matched age, gender, race/ethnicity, and clinical site matched Veterans • All participants alive in 2003 eligible and free of baseline CVD (n=84,832, 33% HIV+) • All AMI outcomes clinically confirmed by IHD QUERI • Validated smoking data, blood pressure and lipid measurements were used

  17. Freiberg et al. CROI. Boston, 2011

  18. Freiberg et al. CROI. Boston, 2011

  19. HIV and the risk of AMI in subpopulations Among never smokers (HR=2.82, 95% CI=1.60-2.38) Among those not on Statin therapy (HR=1.88, 95% CI=1.51-2.34) Among those without hepatitis C, renal disease, or obesity (HR=1.82, 95% CI=1.37-2.40) Freiberg et al. CROI. Boston, 2011

  20. HIV and HCV Co-infection and the Risk of Incident CHD * Incidence rates are age and race/ethnicity adjusted per 1000 person-years Model 1 adjusted for age, race/ethnicity, education, BMI, traditional CHD risk factors, and substance use Model 2 adjusted for all in model 1 plus competing risk of death Freiberg et al. Circ CardiovascularQualityand Outcomes, in press

  21. HCV, ARV, and the risk of AMI among HIV infected men ‡Models adjusted for age, race/ethnicity, education, BMI, traditional CHD risk factors, and substance use Class of ARV (either duration or recent use), HIV viral load, CD4 count, and adjustment for death as a Censoring event or a competing risk Freiberg et al. Circ Cardiovascular Quality and Outcomes, in press

  22. Does HIV infection increase the risk of other cardiovascular diseases?

  23. Increasing incidence of ischemic stroke in patients with HIV Figure 1 Trends in stroke hospitalization by type among persons with a diagnosis of HIV in the United States population 1997-2006(A) Ischemic stroke: trend p value p value = 0.27. (C) Intracerebral hemorrhage: trend p value = 0.88. 2 Ovbiagele et al. Neurology 2011

  24. Alcohol Abuse or Dependence, HIV, and the Risk of Incident Ischemic Stroke Incidence rates are age and race/ethnicity adjusted per 1000 person-years Model adjusted for age, race/ethnicity, education, CVD risk factors, hepatitis C; and DX of cocaine abuse or dependence Freiberg et al. Research Society on Alcoholism Conference, San Antonio, 2010

  25. Which of the following is NOT true about HIV and failure • HIV is associated with a nearly two fold increased risk of heart failure • Ongoing HIV viral replication may play a role • HIV is not associated with heart failure after adjusting for CHD, ischemic cardiomyopathy, and hazardous alcohol consumption

  26. Which of the following is NOT true about HIV and failure • HIV is associated with a nearly two fold increased risk of heart failure • Ongoing HIV viral replication may play a role • HIV is not associated with heart failure after adjusting for CHD, ischemic cardiomyopathy, and hazardous alcohol consumption

  27. HIV and the Risk of Heart Failure Butt et al. Archives of Internal Medicine, 2011

  28. HIV and the Risk of Heart Failure by viral load status Butt et al. Archives of Internal Medicine, 2011

  29. Echocardiographic Parameters by HIV Status Hsue et al. Circ Heart Failure 2010

  30. HIV infection is associated with diastolic dysfunction Hsue et al. Circ Heart Failure 2010

  31. If HIV does increase the risk of CVD what is the mechanism? Do ARVs play a role?

  32. Conceptual Model for HIV and Vascular Risk Baker et al. European Heart Journal 2011

  33. Chronic HIV infection and microbial translocation Brenchley et al. Nature Medicine 2006

  34. Microbial translocation and mortality among HIV infected people* *No adjustment for liver disease or alcohol Sandler et al. JID. 2011

  35. Biomarkers associated with Fatal and Non-Fatal CVD from the SMART Study Hs CRP HR=1.6 (95% CI=0.8-3.1) p=0.20 IL-6 HR=2.8 (95% CI=1.4-5.5) p=0.003 Amyloid A HR=1.6 (95% CI=0.9-2.9) p=0.12 Amyloid P HR=2.8 (95% CI=1.4-5.3) p=0.002 D-dimer HR=2.0 (95% CI=1.0-3.9) p=0.06 Kuller et al. CROI. Boston, 2008

  36. Biomarkers associated with CVD risk among those chronically infected with HIV 2 Ford et al. AIDS 2010

  37. ART Use, Viral Suppression, and CD4 Change Over Follow-Up 2 Baker et al. JAIDS 2011

  38. Median levels of hsCRP (A), IL-6 (B), and D-dimer (C) are presented for VS and DC groups at each visit. Error bars represent the interquartile range (IQR). *P values represent the difference between treatment groups in the change from baseline (on loge scale) and are adjusted for baseline biomarker level. 2 Baker et al. JAIDS 2011

  39. Average change to 1 month in the DC versus VS group in total, large, medium and small HDL-p (μmol/L) by treatment group among HIV infected people. Duprez et al. Atherosclerosis 2009

  40. ARV Therapy and Levels of Inflammatory Biomarkers Baker et al. CROI. Boston, 2011

  41. Do non-traditional risk factors play a role?

  42. The role of alcohol, hepatitis C, and HIV and the risk of AMI Freiberg and Kraemer. Alcohol Research and Health. 2010

  43. Current Alcohol Consumption and HIV VL and Levels of sCD14, IL-6, D-dimer, and Fib4 Score All values are median (25th,75th percentiles) Freiberg et al. ISBRA Conference. Paris, 2010

  44. HCV Status and Levels of sCD14, IL-6, D-dimer, and FIB4 Score pg/ml ng/ml ug/ml Median values for all biomarkers, p values ≤ 0.001 for all Freiberg et al. ISBRA Conference. Paris, 2010

  45. FIB4 Score and Levels of sCD14, IL-6, and D-dimer Freiberg et al. ISBRA Conference. Paris, 2010

  46. The association between HIV and HCV viral load and biomarkers in the HIV LIVE Study Samet et al. ISBRA Conference. Paris, 2010

  47. Correlation between D-dimer, sCD14, IL-6 biomarkers in the VACS* * All associations are significant p<0.001

  48. So, what might you predict next….

  49. Characteristics of SMART, CARDIA, and MESA Study Participants. Neuhaus J et al. J Infect Dis. 2010.

More Related