Cardiovascular Disease:

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• Cardiovascular Disease
• Predicting Risk and Monitoring Outcomes
• Monica R. Shah, MD, FACC
• NHLBI AIDS Coordinator
• Conference on Retroviruses and Opportunistic
  Infections
• March 5, 2013

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Overview

• HIV-Related Cardiovascular Disease (CVD)
• NHLBI AIDS Working Group (WG) Scientific
  Priorities
• NHLBI AIDS Program Future Initiatives

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AIDS An Evolving Population
AIDS Patients Face Downside of Living Longer
January 2008

• In the US 1.2 million people living with HIV
  50,000 new infections each year
• By 2015, HIV patients aged 50 and older will
  account
• for gt50 of HIV/AIDS cases1
• Chronic, non-infectious diseases such as CVD
  increasing public health problem

1 www.cdc.gov Slide courtesy P. Hsue
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HIV-related CVD Significant Mortality

• 1,876 deaths among 39,727 patients
• Non-AIDS related deaths accounted for 50.5
• 16 were due to CVD

Renal 3
Other 9.0
Respiratory 3.1
13 HIV Cohorts 1996-2006
Non-AIDS Malignancy 23.5
Liver-related 14.1
Non-AIDS infection 16.3
Violence, Substance abuse 15.4
CVD 15.7
Antiretroviral Therapy Cohort Collaboration. Clin
Infect Dis. 2010501387-1396 Slide courtesy JS
Currier
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Risk of CVD in HIV vs. Non-HIV Patients
HIV no ART RR 1.61 (1.43-1.81) plt0.001
HIV on ART RR 2.0 (1.7-2.37) Plt0.001
Islam, FM, et al. HIV Medicine 2012 13453-68.
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HIV-Related CV Disease

• Complex interplay between
• Conventional risk factors
• Higher rates of smoking, dyslipidemia,
  hypertension, diabetes
• Obesity
• Renal disease
• Cardio-metabolic adverse effects of ART
• HIV infection
• Inflammation and Immune Activation

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Inflammation and Immune Activation
HIV Infection
Gut microbiome
Aging
Hypercoagulability
Hsue, P et al. The Journal of Infectious Disease.
2012 13 S375-82.
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HIV-Related CV Disease

• Coronary artery disease
• Arrhythmias and sudden cardiac death
• Heart failure
• Pulmonary hypertension
• Hypertension/vascular disease

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NHLBI AIDS Program Mission

• The NHLBI AIDS Program provides global leadership
  for research, training, and education programs to
  promote the prevention and treatment of
  HIV-related cardiovascular, pulmonary, and
  hematologic disease.
• The NHLBI AIDS Program believes that critical
  research in this area will result in discovery
  that enhances the survival and quality of life of
  patients with HIV, and may also lead to
  knowledge that benefits all patients with heart,
  lung, and blood disease.

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NHLBI AIDS WG CV Scientific Priorities
Epidemiology Epidemiology
Scientific Gaps Approaches to Gaps
Incidence/prevalence of HIV-related CVD Utilize existing HIV and CV cohorts to examine questions about HIV-related CVD
Interplay of HIV, inflammation, ART, co-infections, and traditional risk factors on development of HIV-related CVD Enrich HIV cohort studies with data on CV events/imaging and thrombotic events Enrich ongoing CVD studies with HIV patients
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HIV/AIDS WG CV Scientific Priorities
Pathophysiology Pathophysiology
Scientific Gaps Approaches to Gaps
Mechanisms of the interplay of HIV, inflammation, ART, co-infections, and traditional risk factors Studies of these factors in the progression of atherosclerosis Studies of molecular pathways responsible for chronic inflammation Studies of microbial translocation, viral replication, and inflammation in altering lipid metabolism, endothelial function, immune senescence, and thrombosis
Synergy of pathophysiological mechanisms with smoking Mechanistic and imaging studies that elucidate pathogenesis of HIV-related CVD
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NHLBI AIDS WG CV Scientific Priorities
Prevention Treatment Prevention Treatment
Scientific Gaps Approaches to Gaps
Potential differences in the prevention and treatment of CAD Add CV outcomes to HIV trials, increase enrollment of HIV patients in CV trials
Actual efficacy and effectiveness of evidence-based therapies in HIV patients Leverage existing CV databases, claims data, and EHR to evaluate CV patterns of care, variation in prevention, diagnosis, and treatment, post-event outcomes, and implementation of evidence-based care
Appropriate targets for therapy in HIV patients Collaborate with HIV trial networks early during protocol development
Novel therapies to address unique pathophysiology of CAD in HIV patients Conduct pilot trials of novel agents in HIV-related CVD
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NHLBI AIDS WG Research Strategies

• Multi-disciplinary collaboration
• Critical need for HIV and CV researchers to work
  together to advance field
• Leverage existing research resources
• Cross-institute collaboration
• Training
• Training programs that allow clinical and basic
  investigators to learn fundamentals of HIV CVD
  research

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NHLBI Future Initiatives Goal 2014

• Focus on scientific gaps identified by WG
• Broadly stimulate science
• Promote multi-disciplinary collaboration
• Encourage peer-review, investigator-initiated
  research
• Educate scientific community that NHLBI is a
  primary Institute for AIDS research

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Conclusion

• Increasing focus on HIV-related CVD
• Progress in science
• NHLBI uniquely poised to support research in this
  area

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