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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
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
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