The impact of antiretroviral drugs on Cardiovascular Health
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1 The impact of antiretroviral drugs on Cardiovascular Health José López-Sendón Hospital Universitario La Paz. IdiPaz Madrid. Spain Research grants and honoraria from (research committees, clinical trials, personal, Institutional) Lilly / Daiichi-Sankyo, Astra-Zeneca, Sanofi-Aventis, Pfizer, Servier, Novartis, Boehringer Ingelheim, Menarini, Aspen, Merk, Bayer, Lilly
2 The impact Why? How can we measure the risk? How can we prevent / treat?
3 The impact Why? How can we measure the risk? How can we prevent / treat?
4 Early Cardiac manifestations of HIV endocarditis, myocarditis, pericarditis, malignancies
5 Early Cardiac manifestations of HIV endocarditis, myocarditis, pericarditis, malignancies Late CV manifestations Increase of CV risk factors Increase long term prevalence of CV disease
6 50 Prevalence of CV comorbidities in HIV-positive individuals p< HIV-negative individuals (n=349) HIV-positive individuals (n=381) Participants (%) p= p=0.017 p=0.015 p=0.043 p= Hypertension Non-AIDS cancer Angina pectoris Myocardial infarction Peripheral artery disease Other CV disease Cross-sectional analysis of prospective comparative cohort of 381 HIV + individuals and 349 HIV - controls in the Netherlands Schouten et al. IAC Washington, DC. #THAB0205
7 Danish HIV Cohort Study Risk of comorbidity development with age: CVD Myocardial infarction Stroke IR (per 1,000 PYFU) IR (HIV) IR (controls) IR (HIV) IR (controls) Age (years) Age (years) Study of 5,897 HIV-positive individuals and 53,073 controls in the Danish HIV Cohort Study, airr, adjusted incidence rate ratio; IR, incidence rate; PYFU, person-years of follow-up Rasmussen LD et al. Lancet HIV 2015;2:e288 e298
8 Mortality in HIV-positive smokers HIV-positive smokers lose more life-years to smoking than to HIV (12.3 vs 5.1) Probability of survival Age (years) Control, non-smoking Control, smoking HIV, non-smoking HIV, smoking 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, Danish HIV study Helleberg et al. Clin Infect Dis 2013;56:
9 VACS Factors contributing to myocardial infarction HIV-positive (vs HIV-negative) Male (vs female) Diabetes (vs none) egfr <60 (vs 60) ml/min/1.73m 2 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) ahr (95% CI) Clinical prospective study of 83,527 HIV-positive and demographically matched HIV-negative veterans in the USA contributed 453,982 PYFU, 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:
10 The impact Why? How can we measure the risk? How can we prevent / treat?
11 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:e Shahbaz S et al. World J Cardiol 2015;7:
12 D:A:D Link between risk of MI and ART-specific exposure D:A:D study population of 33,308 HIV-positive individuals, followed up from enrolment until the first MI event Relative risk (RR) of MI for different ART RR of recent * exposure Yes/No (95% CI) AZT NRTI Use in HIV treatment DDI DDC D4T 3TC ABC TDF RR of cumulative exposure/year (95% CI) PI IDV NFV LPV/ RTV NNRTI SQV NVP EFV #PYFU: #MI: 138, , , , ,009 53,300 39, #PYFU: #MI: 68, , , , , , TC, 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 fumarate Adapted from Lundgren JD et al. CROI Montreal, Canada. #44LB
13 HIV PATIENTS TODAY AND 10 YEARS AGO: DO THEY HAVE THE SAME NEEDS? 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
14 The impact Why? How can we measure the risk? How can we prevent / treat?
15 Addition of risk factors Multiplies the CV Risk Probability of CV disease Framingham 8 y follow-up Cholesterol Diabetes Systolic BP Smoking LVH in ECG Framingham study
16 The most potent risk factor for future CV events is CV disease itself n=2541 MEN a. 10 YEAR FOLLOW-UP 17,08 Mortality / 1000 / year ,09 4 0,66 0,55 2,74 1,64 Colesterol Pekannen J et al NEJM 1990;322: mg/dl <200 >240 No < yes Known Cardiovascular Disease >240
17 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?
18 VALUE OF THE RISK SCORES?: AWARENESS!
19 The impact Why? How can we measure the risk? How can we prevent / treat?
20 EACS Guidelines
21 EACS Guidelines Muiltifactorial Multidisciplinary
22 Local Protocol, K.I.S.S. rule Smokes.. No Yes Cholesterol (Col >200 / LDL > 115) Hypertension> 140 / 90 mm Hg... No No Yes Yes Any Yes Start treatment Send to specialist if in doubt Diabetes (HbA1C > 6,5).. No Yes CV symptoms?. No Yes Any Yes Known CV disease.. No Yes Send to cardiologist H.U. La Paz, Madrid CARDIOTOX Local Protocol
23 EACS Guidelines The Impact of Antiretroviral Drugs on Cardiovascular Health
24 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
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