HIV e infarto miocardico: un problema dimenticato?
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1 HIV e infarto miocardico: un problema dimenticato? Leonardo Calza Clinica di Malattie Infettive, Policlinico S.Orsola-Malpighi, Università degli Studi di Bologna
2 CVD and HIV disease. The current issues The real size Screening and evaluation Clinical management
3
4 Cardiovascular deaths among HIV-infected patients (percentage of total deaths) 8% 15% France (Lewden C et al., J AIDS 2008) (Palella FJ et al., J AIDS 2006) U.S.
5 Prospective, observational cohort 8,444 HIV-infected patients (Hasse B et al., Clin Infect Dis 2011)
6 Comorbidities Rate per 1000 person-years Non-AIDS defining malignancies 95% C.I Coronary angioplasty Myocardial infarction Cerebral infarction Osteoporosis Liver-associated diseases Kidney-associated diseases (Hasse B et al., Clin Infect Dis 2011)
7 Studies about cardiovascular disease risk in HIV-infected patients compared to the general population Author Year Cohort/ population N. of HIV+ patients Results Klein 2002 Kaiser 4,159 MI and CHD vs control Currier 2003 CA Medicaid 28,513 CHD vs control 2.06 Effect size 1.5 (MI); 1.7 (CHD) Triant 2007 Partners 3,851 MI vs control 1.75 Obel 2007 Danish Cohort 3,953 CHD vs control 2.12 Lang 2010 FHDH 74,958 MI vs control 1.5 Durand 2011 Quebec 7,053 MI vs control 2.11 Freiberg 2013 VA 27,350 MI vs control 1.5
8 Veterans Aging Cohort Study 82,459 HIV-infected patients (Freiberg MS et al., JAMA Intern Med 2013)
9
10 (Silverberg MJ et al., J AIDS 2014) (Kaiser Permanente cohort study: 22,081 HIV+ patients, )
11 Linee guida per il trattamento dell ipercolesterolemia (NCEP, 2004) Colesterolo LDL (mg/dl) FATTORI DI RISCHIO Goal DIETA TERAPIA PER CHD IPOLIPIDICA FARMACOLOGICA Senza CHD: 0-1 fattori di rischio < 160 > 160 > 190 > 2 fattori di rischio -rischio <10% < 130 > 130 > 160 -rischio 10-20% < > 130 > 130 Con CHD o equivalenti: (diabete, rischio > 20%) < > 100 > 100 (Grundy SM, J Am Coll Cardiol 2004)
12
13 The Pooled Cohort Equations to estimate the 10-year and lifetime risk of ASCVD (
14 (Stone NJ et al., Circulation 2013)
15 (Stone NJ et al., Circulation 2013)
16 June 13, 2008
17 Could Russert's death has been prevented? He was being treated for high LDL, low HDL and hypertension; he did not smoke; he did not have diabetes. A stress test in late April was normal. He had even had a calcium scan in 2006, which yielded a calcium score of 210. Autopsy has confirmed LV enlargement and plaque rupture in his LAD. Grady D. A search for answers in Russert's death. New York Times June 17, 2008
18 Traditional risk factors: 1)Age 2) Hypertension 3) Low HDL cholesterol LDL 134 mg/dl
19 30%
20 The Pooled Cohort Equations to estimate the 10-year and lifetime risk of ASCVD
21 (Guaraldi G et al., Abstract OC73, ICAR 2014)
22 Multicenter, cross-sectional study 1182 HIV-positive patients Overall prevalence of hypertension: 29.3% (Am J Hypertens, 2013 Sep 27)
23 HIV, systemic immune activation and endothelial damage (van Leuven SI et al., Current Opin HIV/AIDS 2007)
24 (Hsue PY et al., J Am Heart Assoc 2012) (Case-control study, 347 patients, mean follow-up 2.4 years)
25 (De Luca A et al., BMC Infect Dis 2013) Retrospective, nested, case-control study 109 HIV-infected patients 5-year follow-up
26 (Longenecker CT et al., AIDS 2014) (Cross-sectional study, 147 HIV-positive patients on cart with HIV RNA <1000 copies/ml and LDL-cholesterol <130 mg/dl)
27 (Knudsen A et al., AIDS 2014) (Matched case-control study of 54 cases and 54 controls)
28 Observational, cohort study 9,764 HIV-positive patients with no history of CVD Follow-up: 5 years (Nordell AD et al., J Am Heart Assoc 2014)
29 (Nordell AD et al., J Am Heart Assoc 2014)
30 (Maartens G et al., Lancet 2014) Gastrointestinal tract T CD4+ cell depletion
31 Case-control study 83 HIV-positive patients on HAART vs 88 HIV-negative subjects Age: years (Steele AK et al., PLoS One 2014)
32 Cross-sectional study 60 HIV-positive patients on HAART with viral suppression vs 31 HIV-negative subjects LPS mean level (pg/ml): HIV+ 64 HIV- 50 (p=0.002) (Pedersen KK et al., J AIDS 2013)
33 Role of ART to Prevent CVD Antiretroviral therapy and cardiovascular disease
34 (North Carolina new-user, active-comparator cohort study, 3481 HIV-positive patients) (Brouwer ES et al., Epidemiology 2014)
35
36
37
38 (Med Mal Infect 2013)
39 (Bavinger C et al., PLoS One 2013) (Meta-analysis of 27 studies)
40 (d Arminio Monforte A et al., AIDS 2013) (D:A:D Study)
41 (North Carolina new-user, active-comparator cohort study, 3481 HIV-positive patients) (Brouwer ES et al., Epidemiology 2014)
42 Research interventions to reduce inflammation in HIV patients on cart Chemokine receptor inhibitors: maraviroc, TB-652 Anti-infective therapy: CMV, EBV, HSV, HBV, HCV Microbial translocation: sevelamer, colostrum, rifaximin, pre-biotics, probiotics, isotretinoin Enhance T cell renewal: growth hormone, IL-7 Anti-fibrotic drugs: perfenidone, ACEinhibitors, ARBs Anti-aging: caloric restriction, diet,sirtuin activators, vitamin D, omega-3 fatty acids, sirolimus, exercise Anti-inflammatory drugs Anti-coagulants: low dose warfarin, dabigatran, aspirin, clopidogrel
43 Anti-inflammatory drugs Chloroquine, hydroxychloroquine Minocycline NSAIDs (COX-2 inhibitors), aspirin Statins Methotrexate (low-dose; CIRT) Talidomide, lenalidomide, pentoxyfylin
44 (Calza L et al., HIV Clin Trials 2014) (Observational, cohort study, 86 patients, 12-month follow-up)
45 (Calza L et al., AIDS Res Hum Retroviruses 2012) -Observational, cohort study -36 patients -2-year follow-up
46 (Ganesan A et al., J Infect Dis 2011) (Double-blind, randomized trial: 24 naive patients)
47 (SATURN-HIV randomized, double-blinded, placebo-controlled trial; 147 HIV+ patients) Stable cart (>12 weeks) LDL cholesterol <130 mg/dl hscrp >2 mg/l and/or CD8+ cell activation (Eckard AR et al., J Infect Dis 2014)
48 (Eckard AR et al., J Infect Dis 2014)
49 (Fundferburg NT et al., Clin Infect Dis 2014)
50 (J Infect Dis 2014; 209: )
51 -Case-control study -25 HIV-positive patients with HIV RNA <50 copies/ml and 44 healthy controls (O Brien M et al., J AIDS 2013)
52 (Cross-sectional study, 397 patients) Patients in need receiving aspirin: 17% (Burkholder GA et al., Clin Infect Dis 2012)
53 (Nemerovski CW et al., Pharmacotherapy 2012)
54 Conclusions. The current challenges The correct assessment of CDV risk in HIV+ patients The best markers for chronic inflammation and CVD risk in HIV The best treatment to reduce HIV-associated inflammation and CVD risk Assess, prevent and treat
55 Grazie per l attenzione.
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