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Cardiovascular Complications of HIVMark Boyd MD, FRACPThe Kirby Institute for infection and immunity in society7th IAS Conference Kuala Lumpur, Malaysia03 July 2013
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Cardiovascular Complications of HIVConflicts of interestGrants HonorariaAbbVie AbbVie
Gilead Sciences Boehringer-Ingelheim
Merck Bristol Myers Squibb
Janssen-Cilag
Merck
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Cardiovascular Complications of HIVOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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Cardiovascular Complications of HIVOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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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
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Cardiovascular ComplicationsOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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Risk factors CVD HIV+ vs HIV-
Kaplan R, et al. CID 2007.
Dyslipidaemia
Smoking
Insulin resistance
HIV-neg menHIV-pos men
HIV-neg womenHIV-pos. women
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Comorbidity distribution
*
Schouten J et al. World AIDS Conference July 2012;updated May 2013 (personal communication, Reiss P)
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Cardiovascular ComplicationsOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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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
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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
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Untreated HIV infection and CVD pathogenesis: a proposed model
Baker J and Lundgren J. Eur Heart J 2011
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Cardiovascular ComplicationsOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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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
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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
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Untreated HIV infection and CVD pathogenesis: a proposed model
Baker J and Lundgren J. Eur Heart J 2011
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Treated HIV infection and CVD pathogenesis: a proposed model
Baker J and Lundgren Eur Heart J. 2011
ART Insulin resistance
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Cardiovascular ComplicationsOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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IRR1.73
3.403.73 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
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Cardiovascular disease in HIVPrevention: monitor and modify risks
Petoumenos K for D:A:D . 20th CROI 2013.
12
34
56
Rel
ativ
e H
azar
d
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
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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.
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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 0Score 2
Score 3 & 4
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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
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Cardiovascular ComplicationsOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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CVD complications of HIV: key messages
Walker S, et al. DART. Lancet 2009.
ART saves lives
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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
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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
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Cardiovascular ComplicationsOutline• Epidemiology• Risk factors
– host– virus-host– ART
• Prevention• Key messages• Conclusions
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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
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