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The impact of antiretroviral drugs on Cardiovascular...
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The Impact of Antiretroviral Drugs on Cardiovascular Health
José López-SendónHospital Universitario La Paz. IdiPaz
Madrid. Spain
The impact of antiretroviral drugs on Cardiovascular Health
Research grants and honoraria from (research committees, clinical trials, personal, Institutional)
Lilly / Daiichi-Sankyo, Astra-Zeneca, Sanofi-Aventis, Pfizer, Servier, Novartis, BoehringerIngelheim, Menarini, Aspen, Merk, Bayer, Lilly
The Impact of Antiretroviral Drugs on Cardiovascular Health
• The impact
• Why?
• How can we measure the risk?
• How can we prevent / treat?
The Impact of Antiretroviral Drugs on Cardiovascular Health
• The impact
• Why?
• How can we measure the risk?
• How can we prevent / treat?
The Impact of Antiretroviral Drugs on Cardiovascular Health
• ¨Early¨ Cardiac manifestations of HIV endocarditis, myocarditis, pericarditis, malignancies
The Impact of Antiretroviral Drugs on Cardiovascular Health
• ¨Early¨ Cardiac manifestations of HIV endocarditis, myocarditis, pericarditis, malignancies
• Late CV manifestations• Increase of CV risk factors• Increase long term prevalence of CV disease
The Impact of Antiretroviral Drugs on Cardiovascular Health
Prevalence of CV comorbidities in HIV-positive individuals
Schouten et al. IAC 2012. Washington, DC. #THAB0205
Hypertension Non-AIDS cancer
Angina pectoris
Myocardialinfarction
Peripheralartery
disease
Other CVdisease
Part
icip
ants
(%)
0
20
30
40
50
10
p<0.0001
p=0.010
p=0.017p=0.015
p=0.043p=0.034
HIV-negative individuals (n=349)
HIV-positive individuals (n=381)
Cross-sectional analysis of prospective comparative cohort of 381 HIV + individuals and 349 HIV - controls in the Netherlands
The Impact of Antiretroviral Drugs on Cardiovascular Health
Study of 5,897 HIV-positive individuals and 53,073 controls in the Danish HIV Cohort Study, 1995–2014
Danish HIV Cohort StudyRisk of comorbidity development with age: CVD
aIRR, adjusted incidence rate ratio; IR, incidence rate; PYFU, person-years of follow-upRasmussen LD et al. Lancet HIV 2015;2:e288–e298
5.0
4.0
3.0
2.0
1.0
0
25.0
20.0
15.0
10.0
5.0
0
18.0
15.0
12.0
9.0
6.0
3.0
0
6.0
5.0
4.0
3.0
2.0
1.0
0
16–44 ≥6545–54 55–64
Age (years)
IR (
per
1,0
00
PY
FU)
Myocardial infarction
IR (HIV)
IR (controls)
16–44 ≥6545–54 55–64
Age (years)
Stroke
IR (HIV)
IR (controls)
The Impact of Antiretroviral Drugs on Cardiovascular Health
Population-based cohort study of 2,921 HIV-positive individuals from the Danish HIV Study and 10,642 controls from the Copenhagen General Population Study, 1995–2010
Mortality in HIV-positive smokersHIV-positive smokers lose more life-years to smoking than to HIV (12.3 vs 5.1)
Danish HIV studyHelleberg et al. Clin Infect Dis 2013;56:727‒734
1.00
0.75
0.50
0.25
0.00
Prob
abili
ty o
f sur
viva
l
35 40 45 50 55 60 65 70 75 80Age (years)
HIV, smoking
HIV, non-smoking
Control, smoking
Control, non-smoking
The Impact of Antiretroviral Drugs on Cardiovascular Health
Clinical prospective study of 83,527 HIV-positive and demographically matched HIV-negative veterans in the USA contributed 453,982 PYFU, 2003–2010
VACSFactors contributing to myocardial infarction
aHR, adjusted hazard ratios; CI, confidence interval; eGFR, estimated glomerular filtration; PYFU, person-years of follow-up; VACS, Veterans Aging Cohort Study
Althoff KN et al. Clin Infect Dis 2015;60:627–638
0.00 1.00 2.00 3.00 4.00 5.00
aHR (95% CI)
HIV-positive (vs HIV-negative)
Male (vs female)
Diabetes (vs none)
eGFR <60 (vs ≥60) mL/min/1.73m2
Current (vs never) smoking
Past (vs never) smoking
Hypertension (vs none)
Hyperlipidemia (vs none)
Hepatitis C infection (vs none)
Black race (vs white)
Other race (vs white)
The Impact of Antiretroviral Drugs on Cardiovascular Health
• The impact
• Why?
• How can we measure the risk?
• How can we prevent / treat?
The Impact of Antiretroviral Drugs on Cardiovascular Health
HIV
Reasons for CV disease increase in long term survivors
• HIV direct effect: Imflammation, metabolic, endothelial damage
• ART: toxicity on myocardium, metabolism, vessels, thrombotic
• Aging: longer life expectancy more CV risk & disease
• Permisive life style: sedentarism, diet, smoke, neglet risk factors
De Gaetano Donati K et al. J Hematol Infect Dis 2010;2:e2010034Shahbaz S et al. World J Cardiol 2015;7:633–644
The Impact of Antiretroviral Drugs on Cardiovascular Health
D:A:D study population of 33,308 HIV-positive individuals, followed up from enrolment until the first MI event
D:A:DLink between risk of MI and ART-specific exposure
3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; AZT, zidovudine; CI, confidence interval; D4T, stavudine; DDC, zalcitabine; DDI, didanosine; EFV, efavirenz; IDV, indinavir; LPV, lopinavir; MI, myocardial infarction; NFV, nelfinavir; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NVP, nevirapine; PI, protease inhibitor; PYFU, patient-years of follow-up; RTV, ritonavir; TDF, tenofovir disoproxil fumarateAdapted from Lundgren JD et al. CROI 2009. Montreal, Canada. #44LB
Relative risk (RR) of MI for different ART
RR
of
cum
ula
tive
ex
pos
ure
/ye
ar (
95
% C
I) 1.2
1.131.1
1.0
0.9
PI‡ NNRTI
IDV NFV LPV/RTV
SQV NVP EFV
68,469298
56,529197
37,136150
44,657221
61,855228
58,946221
#PYFU:#MI:
RR
of
rece
nt*
exp
osu
reY
es/
No
(95
% C
I)
1.9
1.5
1.2
1.0
0.8
0.6
†
Use in HIV treatment
1.9
1.5
1.2
1.0
0.8
0.6
NRTI
AZT DDI DDC D4T 3TC ABC TDF
138,109523
74,407331
29,676148
95,320405
152,009554
53,300221
39,157139
#PYFU:#MI:
The Impact of Antiretroviral Drugs on Cardiovascular Health
French ANRS CO3 Aquitaine prospective cohort, 10 years apart, observed both in 2004 and in 2014
Significant improvement in HIV markers over time, in a population getting older
HIGHER prevalence of comorbidities, (dyslipidaemia, hypertension) with increased associated risk factors and renal and cardiovascular risk scores more pronounced
Bonnet. Glasgow 2016
HIV PATIENTS TODAY AND 10 YEARS AGO: DO THEY HAVE THE SAME NEEDS?
The Impact of Antiretroviral Drugs on Cardiovascular Health
• The impact
• Why?
• How can we measure the risk?
• How can we prevent / treat?
The Impact of Antiretroviral Drugs on Cardiovascular Health
Addition of risk factors Multiplies the CV RiskProbability of CV disease
Cholesterol 185 335 185 335 185 335 185 335Diabetes 0 + + +Systolic BP 105 195 195 195Smoking 0 0 + +LVH in ECG 0 0 0 +
Framingham8 y follow-up
Framingham study
The Impact of Antiretroviral Drugs on Cardiovascular Health
Mortality/ 1000 / year
41,64
20
16
12
8
0
mg/dl >240<200200-240
9,09
0,66 0,55
2,74
17,08
Known Cardiovascular Diseaseyes
ColesterolNo
>240<200200-240
n=2541 MEN 40-69 a.10 YEAR FOLLOW-UP
Pekannen J et alNEJM 1990;322:1700
The most potent risk factor for future CV events is CV disease itself
The Impact of Antiretroviral Drugs on Cardiovascular Health
Risk Scores• Framinham?• European Society of Cardiology SCORE?• D.A.D. score?, EUROsida, Other HIV score?• K.I.S.S. rule?• Use your fingers counting risk factors?• Forget about scores and always treat each risk factor?
http://www.hivpv.org/Home/Tools/tabid/91/ctl/ExamView/mid/500/eid/0/lid/0/Default.aspx
The Impact of Antiretroviral Drugs on Cardiovascular Health
VALUE OF THE RISK SCORES?:AWARENESS!
The Impact of Antiretroviral Drugs on Cardiovascular Health
• The impact
• Why?
• How can we measure the risk?
• How can we prevent / treat?
The Impact of Antiretroviral Drugs on Cardiovascular Health
EACS Guidelines
The Impact of Antiretroviral Drugs on Cardiovascular Health
EACS GuidelinesMuiltifactorialMultidisciplinary
The Impact of Antiretroviral Drugs on Cardiovascular Health
• Smokes ……………………………..
• Cholesterol (Col >200 / LDL > 115)
• Hypertension> 140 / 90 mm Hg ...
• Diabetes (HbA1C > 6,5) …………..
• CV symptoms? …………………….
• Known CV disease ………………..
YesNo
YesNo
YesNo
YesNo
YesNo
Any ¨Yes¨• Start treatment• Send to specialist if in doubt
YesNo
Any ¨Yes¨
• Send to cardiologist
Local Protocol, K.I.S.S. rule
H.U. La Paz, MadridCARDIOTOX Local Protocol
The Impact of Antiretroviral Drugs on Cardiovascular Health
EAC
S G
uide
lines
The Impact of Antiretroviral Drugs on Cardiovascular Health
Conclusions
• CV risk increased in HIV w/wout ARTs
• Use ARTs as indicated
• Awarenes of increase in risk factors
• Healthy life style
• Early identification & treatment of risk factors