1. Pharmacological approaches to improve cardiovascular health

2. Bacterial Translocation CD4 Nadir Abacavir
Chronic Inflammation 
Antiretrovirals 
HRM Plaque 
LDL
Smoking
Inflammaging
Bacterial Translocation
Methotrexate 
CD4 Nadir
Abacavir 
Protease Inhibitors
Immune Activation 
Blood Pressure Control
CMV co-infection
HIV viremia 
HDL
Biomarkers 
Statins
CAD-10 yr Risk
Monocytes

3. HIV viremia, CD4 counts associated with poor CVD outcomes
Traditional
risk
Persons with well-controlled viremia still have worse CVD outcomes than uninfected 
HIV
HIV viremia, CD4 counts associated with poor CVD outcomes 
ART
Less of an issue with transition to INSTI
Abacavir?

4. Address chronic inflammation and immune activation
Traditional
risk
Address chronic inflammation and immune activation
HIV
Viral suppression
CD4 recovery
ART
Benefits outweigh risk

5. Anti-inflammatory Agents
Traditional
risk
Immunomodulators 
Anti-inflammatory Agents
HIV
Antiretrovirals
ART
Benefits outweigh risk

6. Traditional
risk
HIV
ART

7. Manage Blood Pressure
Control Cholesterol

11. According to the World Health Organization, what percentage of adults (ages 18-74) have high blood pressure? 8%
13%
18%
22%
 44%

12. According to the World Health Organization, what percentage of adults (ages 18-74) have high blood pressure? 8%
13%
 18%
 22%*
 44%

13. Author (Year)
Country
Sample Size
HIV-negative
PLWH
Seaberg et al. (2005) 
5578
n/a
7.3%
Triant et al. (2007)  
26,142
15.9%
21.2%
Malaza et al (2012)
3090
14.5%
10.2%
Kavishe et al. (2015)
2011
16-26%
van Zoest et al. (2016) 
1044
36.4%
48.2%

15. For every 20-point increase in systolic blood pressure, what is the relative increase in risk of death from a heart attack in the next 10 years?
10%
30%
50%
75%
100%

16. For every 20-point increase in systolic blood pressure, what is the relative increase in risk of death from a heart attack in the next 10 years?
10%
30%
50%
75%
100%
Lancet 2002; 360: 1903–13

19. Hypertension. 2018;71: ​

20. 130/80

21. Home BP Monitoring
What are your numbers?

22. Who should be treated for high blood pressure?
Hypertension. 2018;71:

23. Home Blood Pressure is More Predictive of 5-year Risk of Death
Banegas et al. NEJM, 2018

24. Pharmacologic Agents for High BP Treatment
Thiazide Diuretics
Calcium Chanel Blockers
ACE-Inhibitors
Angiotensin Receptor Blockers
Beta-blockers

25. Thiazide Diuretics Loss of salt and water in urine
Shown to decrease CVD events
Very well-tolerated
Side effects: Increased urinary frequency and electrolyte imbalances
Minimal interaction with antiretrovirals

26. Calcium Channel Blockers
Dilate blood vessels (arteries)
Side effects: swelling in extremities, headache, flushing
May be better for blood pressure lowering among persons with hypertension of African descent
NNRTIs can lower blood levels of CCBs
PIs/cobicistat can raise blood levels of CCBs

27. ACE-Inhibitors/Angiotensin II Receptor Blockers
Prevents retention of water in the kidneys & constriction of blood vessels
Side effects: Cough, High Potassium, Kidney Injury, Angioedema
Used in treatment of MI, heart failure
Very good for BP treatment in diabetics
PIs/cobicistat can raise blood levels of losartan

28. 22% 6% 24% 50% 58% What about Aspirin? Decrease in non-fatal MI
over 10 years
Decrease in all-cause
mortality
Decrease in colon cancer over 20 years
50%
58%
Increase in non-fatal
intracranial bleed
Increase in gastrointestinal bleed
Although evidence of increased platelet activation in HIV, no clear evidence of added benefit of aspirin in this population 
Guirguis-Blake et al., Ann Intern Med, 2016
Rothwell et al., Lancet, 2010 
O'Brien et al., Open Forum Infect Dis, 2017

29. United States Preventative Services Task Force, 2016
“Aspirin cannot be recommended in primary prevention due to its increased risk of major bleeding”
“Low-dose aspirin is recommended for individuals aged 50 to 59 years of age who have a 10 percent or greater 10-year risk of CVD risk, who are not at increased risk for bleeding, who have a life expectancy of 10 years, and who are willing to take aspirin for 10 years”
“The evidence to recommend aspirin in a population aged 60 to 69 years is less robust and the decision should be individualized”
“In adults younger than 50 or older than 70 years, the evidence is insufficient to make a recommendation.”
United States Preventative Services Task Force, 2016
European Society of Cardiology, 2016

30. Cholesterol Precursors
Statins
Cholesterol lowering medications
Have been shown to lower “bad cholesterol” up to 60%
Decreases risk of MI, stroke and all cause mortality
Side effects: liver inflammation, muscle pain/breakdown, impaired glucose tolerance
Cholesterol
Cholesterol Precursors
HMG CoA Reductase

31. Protease Inhibitors and Cobicistat Increase Blood Levels of Statins
Lovastatin
Simvastatin  
CONTRAINDICATED
Atorvastatin
Rosuvastatin
CAUTION
Pravastatin Pitavastatin 
NO INTERACTION

32. Indication for Statin LDL > 190 10-yr CVD risk > 7.5% Statin
Prior CAD
Diabetes
Circulation. 2014; 129: S1-S45

33. Pooled Cohort Equations Calculator
Risk calculators underestimate risk in persons living with HIV.
tools.acc.org/ascvd-risk-estimator-plus

34. Statin and HIV Decreases inflammatory biomarkers
Decreases plaque volume in coronary arteries
Slows plaque buildup in carotid arteries
Decreases monocyte activation
Preserves renal function
Increases bone mineral density
Eckard et al. (2014)
Lo et al. (2015)
Funderburg et al (2014)
Longenecker et al. (2016)
Longenecker et al. (2014)

35. What else do statins do?

36. In persons without high cholesterol and high inflammation (elevated CRP), statins decreased risk of MI, stroke or cardiovascular death by 44%
Ridker et.al, NEJM, 2008 

37. 110+ Sites Across US, Canada, Thailand, Brazil,
South Africa, Zimbabwe, Uganda, Botswana, Peru and Haiti
Opened April 2015
Many in the room are aware of this large randomized trial of statin therapy to reduce hard vascular events in HIV

38. Indications for Statin Use
LDL > 190
HIV
10-yr CVD risk > 7.5%
Statin
Prior CAD
Diabetes
Circulation. 2014; 129: S1-S45

39. Other agents PCSK-9 inhibitors (evolucumab) Ezetimibe Canakinumab
Methotrexate?
Ridker et al, NEJM, 2017

40. Take Home Points Know your numbers
Be informed to get the most out of your doctor visits
Medications work and have relatively few interactions
Not many HIV-specific interventions but more may be on the way
Focus on what you can change!!