Cardiovascular Complications of HIVMark Boyd MD, FRACPThe Kirby Institute for infection and immunity in society7th IAS Conference Kuala Lumpur, Malaysia03 July 2013

Cardiovascular Complications of HIVConflicts of interestGrants Honoraria

AbbVie AbbVie

Gilead Sciences Boehringer-Ingelheim

Merck Bristol Myers Squibb

Janssen-Cilag

Merck

Cardiovascular Complications of HIVOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

Cardiovascular Complications of HIVOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

Myocardial Infarction rates in HIV+ versus HIV-

Triant J, et al. Clin Endocrinol Metab. 2007.

Mean MI rate = 11 v 7 per 1000 person yearsRR=1.7

Cardiovascular ComplicationsOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

Risk factors CVD HIV+ vs HIV-

Kaplan R, et al. CID 2007.

Dyslipidaemia

Smoking

Insulin resistance

HIV-neg men

HIV-pos men

HIV-neg women

HIV-pos. women

Comorbidity distribution

*

Schouten J et al. World AIDS Conference July 2012;updated May 2013 (personal communication, Reiss P)

Cardiovascular ComplicationsOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

0.1 1 10

SMART - major CVD, hepatic or renal diseaseNo. of patients

with eventsEndpoints

Major CVD, hepatic or renal disease 104

CVD, fatal or non-fatal 79

Favours VS ►

►

Favours DC

Relative risk (95% CI)

Renal disease, fatalor non-fatal 11

1.6

Hepatic disease, fatal or non-fatal 17

4.5

1.4

1.7

El-Sadr W, et al. SMART. NEJM 2006

Cardiovascular complications of HIVSMART: risk of death strongly associated with IL-6 & D-dimer biomarker levels at study entry

Biomarker <25th percentile(reference)

25th-49th

percentile50th-74th

percentile>75th

percentilep-value

OR (95%CI)

OR (95t% CI)

OR(95% CI)

IL-6(inflammation)

1.0 1.5(0.7-3.1)

3.2(1.3-7.9)

8.3(3.3-20.8)

<0.0001

D-dimer(coagulation)

1.0 3.2(1.1-9.0)

4.0(1.3-12.3)

12.4(4.3-37.0)

<0.0001

Kuller L, et al. PLoS Med 2008

Untreated HIV infection and CVD pathogenesis: a proposed model

Baker J and Lundgren J. Eur Heart J 2011

Cardiovascular ComplicationsOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

Cardiovascular complications of HIVART and myocardial infarction

Friis-Moller N, et al. D:A:D. NEJM 2003. MI incidence according to duration of ART exposure

MI risk disease by ARV exposure in D:A:D

Worm S, et al. D:A:D. JID 2012.

ART exposure and MI risk in D:A:D

Cardiovascular complications of HIV

Untreated HIV infection and CVD pathogenesis: a proposed model

Baker J and Lundgren J. Eur Heart J 2011

Treated HIV infection and CVD pathogenesis: a proposed model

Baker J and Lundgren Eur Heart J. 2011

ART Insulin resistance

Cardiovascular ComplicationsOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

IRR1.73

3.40

3.73 3.0

0 2.07

2.62

Myocardial Infarction

Never smoked

5 -

1 -

Previous

Baseline status

< 1 yr 1-2 yrs 2-3 yrs 3+ yrsCurrent

Stopped smoking during follow-up

Adjusted for: age, sex, cohort, calendar year, antiretroviral treatment, family history of CVD, diabetes, and time-updated lipids and blood pressure assessments

0.5 -

D:A:D study group. HIV Med 2011.

Stop Smoking

Cardiovascular disease in HIVPrevention: monitor and modify risks

Petoumenos K for D:A:D . 20th CROI 2013.

12

34

56

Rela

tive

Haza

rd

40 45 50 55 60 65age

Reduce TC 1 mmol/L

Stop smoking

CVD hazard in D:A:D*Reduce sysBP 10 mmHg

*relative to 40 y.o. HIV+ male

Control dyslipidaemia: use TDFTDF

(n=170)d4T

(n=162)p-value

Total-cholesterol (mmol/L) +0.78 +1.50 <0.001HDL-cholesterol (mmol/L) +0.23 +0.16 0.003LCL-cholesterol (mmol/L) +0.36 +0.67 <0.001TG (mmol/L) +0.01 +1.51 <0.001Total limb fat gain-DXA (kg) +8.6 +4.5 <0.001Total weight gain (kg) +2.9 +0.6 0.001Neuropathy 3% 10% <0.001

Gallant J, et al. GS 934 study. JAMA 2004;292:191-201.

CVD complications of HIV

Ahmed H et al. MESA. Am J Epi 2013.

Prevention: adopt a healthy lifestyle

Probability of CHD according to health score

Score 0

Score 2

Score 3 & 4

CVD complications of HIV

Ahmed A, et al. MESA. Am J Epi 2013.

Prevention: adopt a healthy lifestyle

Probability of death according to health score

Score 3 & 4

Score 2

Score 1Score 0

Cardiovascular ComplicationsOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

CVD complications of HIV: key messages

Walker S, et al. DART. Lancet 2009.

ART saves lives

CVD complications of HIV: key messages

3 year risk Off ART On ARTAIDS/Death 23 - 29% 6 - 11%

AMI 0.3% (0.2-0.38)

1% (0.43-1.77)

Law M et al. HIV Med 2003.

The risk of death from AMI is much less than the risk of dying from untreated HIV-infection

CVD complications of HIV: key messagesMonitor and treat modifiable risk factors• Stop smoking• Monitor& treat hypertension• Monitor & treat dyslipidaemia and diabetes• Encourage healthy weight, diet and exercise• Monitor and treat HIV-infection

– according to guidelines– there is no evidence to support use of specific ART

regimens for PLHIV with high-risk for CVD

Cardiovascular ComplicationsOutline• Epidemiology• Risk factors

– host– virus-host– ART

• Prevention• Key messages• Conclusions

Cardiovascular Complications of HIVConclusions• Cardiovascular disease pathogenesis in HIV

is complex• While HIV factors may add to complexity,

conventional risk factors are prominent• Risks can be monitored and modified • Primary prevention is key in low-, middle-

and high-income settings