Cardiovascular Disease: Predicting Risk and Monitoring Outcomes

Monica R. Shah, MD, FACCNHLBI AIDS Coordinator

Conference on Retroviruses and Opportunistic InfectionsMarch 5, 2013

HIV-Related Cardiovascular Disease (CVD)

NHLBI AIDS Working Group (WG) – Scientific Priorities

NHLBI AIDS Program – Future Initiatives

Overview

2

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 >50% of HIV/AIDS cases1

Chronic, non-infectious diseases such as CVD increasing public health problem

1 www.cdc.gov; Slide courtesy P. Hsue

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

13 HIV Cohorts1996-2006

CVD15.7%

Non-AIDSinfection

16.3%

Non-AIDSMalignancy

23.5%

Violence, Substance

abuse 15.4%

Liver-related14.1%

Other

9.0%Respiratory

3.1%

Renal3%

Antiretroviral Therapy Cohort Collaboration. Clin Infect Dis. 2010;50:1387-1396Slide courtesy JS Currier

Risk of CVD in HIV vs. Non-HIV Patients

HIV – no ARTRR 1.61 (1.43-1.81)

p<0.001

HIV – on ARTRR 2.0 (1.7-2.37)

P<0.001

Islam, FM, et al. HIV Medicine; 2012; 13:453-68.

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

HIV-Related CV Disease

Inflammation and Immune Activation

Gut microbiome

Hypercoagulability Aging

HIV Infection

Hsue, P et al. The Journal of Infectious Disease. 2012; 13: S375-82.

Coronary artery disease

Arrhythmias and sudden cardiac death

Heart failure

Pulmonary hypertension

Hypertension/vascular disease

HIV-Related CV Disease

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.

NHLBI AIDS Program – Mission

NHLBI AIDS WG: CV Scientific Priorities

EpidemiologyScientific 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

HIV/AIDS WG: CV Scientific Priorities

PathophysiologyScientific 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

NHLBI AIDS WG: CV Scientific Priorities

Prevention & Treatment

Scientific Gaps Approaches to GapsPotential 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

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

NHLBI AIDS WG: Research Strategies

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

NHLBI Future Initiatives – Goal 2014

Conclusion

Increasing focus on HIV-related CVD

Progress in science

NHLBI uniquely poised to support research in this area