The impact of antiretroviral drugs on Cardiovascular Healthregist2.virology-education.com/2017/HealthyLiving/... · The Impact of Antiretroviral Drugs on Cardiovascular Health. Population-based

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

• Why?

• How can we measure the risk?

• How can we prevent / treat?


• The impact

• Why?




• Ëarly¨ Cardiac manifestations of HIV endocarditis, myocarditis, pericarditis, malignancies


• Ëarly¨ Cardiac manifestations of HIV endocarditis, myocarditis, pericarditis, malignancies

• Late CV manifestations• Increase of CV risk factors• Increase long term prevalence of CV disease


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


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)


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


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

• Why?




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


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:


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

• Why?




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


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


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


VALUE OF THE RISK SCORES?:AWARENESS!


• The impact

• Why?




EACS Guidelines


EACS GuidelinesMuiltifactorialMultidisciplinary


• 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 Ÿes¨• Start treatment• Send to specialist if in doubt

YesNo

Any Ÿes¨

• Send to cardiologist

Local Protocol, K.I.S.S. rule

H.U. La Paz, MadridCARDIOTOX Local Protocol


EAC

S G

uide

lines


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

The impact of antiretroviral drugs on Cardiovascular Healthregist2.virology-education.com/2017/HealthyLiving/... · The Impact of Antiretroviral Drugs on Cardiovascular Health. Population-based

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