Eventi cerebro-vascolari: davvero una nuova frontiera?

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1 Eventi cerebro-vascolari: davvero una nuova frontiera? Leonardo Calza Clinica di Malattie Infettive, Policlinico S.Orsola-Malpighi, Università di Bologna

2 (Lancet 2016) Changes in leading 30 causes of death, 2005 to 2015

3 (Lancet Infect Dis 2015)

4 Age-standardized stroke incidence Nature Reviews Neurology 2014 HIV infection and stroke: an intersection of epidemics (Felicia C. Chow)

5 HIV infection and cerebrovascular diseases: critical issues Epidemiology of stroke in HIV infection Proposed mechanisms underlying elevated stroke risk in HIV infection cart impact on stroke risk Cerebrovascular disease and neucognitive disorders Prevention strategies

6 Risk of cerebrovascular diseases among HIV-infected patients in the pre-cart era (Case-control study; ) Odds Ratio OR, 3.4 (95% CI, ) OR, 2.3 (95% CI, 1-5.3) (Qureshi AI et al., Arch Neurol 1997)

7 (Okeke NL et al., J Infect Dis 2016) U.S. National Inpatient Sample (NIS) 18,369,785 AMI/stroke hospitalizations

8 (Hasse B et al., Clin Infect Dis 2011)

9 Increased incidence of stroke in the cart era Improved survival and aging of the HIV-positive people High prevalence of comorbidities High prevalence of traditional risk factors (mostly dyslipidemia, smoking and substance abuse) HIV-associated vasculopathy cart-induced vascular damage Cerebral vasculitis from concomitant infections (syphilis, CMV, tuberculosis)

10 CNICS U.S. Multisite Clinical Cohort HIV-infected patients 312 strokes (Crane HM et al., Abstract 347, CROI 2017)

11 (Sico JJ et al., Neurology 2015) Veterans Aging Cohort Study-Virtual Cohort male patients, Median follow-up: 5.9 years

13 Case control study 60 HIV-positive and 60 HIVnegative patients with firstever ischemic stroke (Chow FC et al., J Stroke Cerebrovasc Dis 2017)

14 (Benjamin LA et al., Neurology 2016) Case-control study Malawi 222 adults with acute stroke and 503 population controls Median age: years HIV prevalence: 31% in cases, 19% in controls

16 (Fitch KV et al., J Infect Dis 2013) Case-control study 90 women and 143 men (mean age, 47 years) HIV-positive group: HIV RNA<50 cp/ml in the 87% of cases Coronary CT angiography and immune activation markers

17 HIV-positive women Cross-sectional study 49 HIV-positive and 25 HIVnegative women Coronary CT angiography and immune activation markers (Looby SE et al., AIDS 2016)

18 HIV+ status alone 5 eligible studies ,426 person-years evaluated Pooled crude incidence ratio for ICH in HIV/AIDS: 3.40 (95% CI , p=0.005) AIDS status alone (Behrouz R et al., J Neurovirol 2016)

19 Mortality rates for stroke U.S. National Inpatient Sample (NIS) 1,874,067 stroke hospitalizations (Kucab P et al., J Stroke Cerebrovasc Dis 2017)

20 Stroke-associated hospitalizations U.S. National Inpatient Sample (NIS) 18,369,785 AMI/stroke hospitalizations (Okeke NL et al., J Infect Dis 2016)

22 HIV-associated vasculopathy A,B- atherosclerotic vasculopathy C- HIV-associated vasculitis D- small vessel disease: arteriolosclerosis E- small vessel disease: lipohyalinosis F- non-atherosclerotic vasculopathy (Benjamin LA et al., Neurol Neuroimmunol Neuroinflamm 2016)

23 (Benjamin LA et al., Lancet Neurol 2012) HIV-associated vasculopathy

24 Cross-sectional study 81 patients HIV+ patients on cart and with HIV RNA<48 cp/ml; mean CD4 count 641 cells/mmc Cardiac 18 F-FDG-PET and coronary CT scan Serum inflammatory markers (Subramanian S et al., JAMA 2012)

25 Association between cart and cerebrovascular events in cohort studies Reference Study No. of patients Results D Arminio Monforte, 2004 D:A:D Increased incidence of CVD with exposure to cart (no association bewteen cart and stroke) Bozzette, 2003 Veterans No relation between cart (NRTI, NNRTI or PI) and risk of CV events Rasmussen LD, 2011 Danish Cohort 5031 Abacavir associated with increased risk of CV events Choi AI, 2011 Veterans Abacavir associated with increased risk of CV events

28 (Chow FC et al., J AIDS 2017) -Case control study -78 HIV-positive patients on cart and with undetectable HIV RNA -18 HIV-negative controls

30 (Ryom L et al., Abstract 128LB, CROI 2017)

31 (Bertrand L et al., Sci Rep 2016)

32 HIV infection Cerebrovascular diseases HAND Neurocognitive symptoms

33 (Wright EJ et al., Neurology 2010) SMART Substudy 292 HIV+ patients 92% on cart Median CD4 count: 536 cells/mm 3 88% with HIV RNA <400 cp/ml

34 (Dufouil C et al., Neurology 2015) ANRS CO3 Aquitaine Cohort HIV+ patients 2-year follow-up

35 Cross-sectional study 103 aviremic HIV-infected men on cart vs 70 HIV-negative controls (Su T et al., AIDS 2016)

36 Stroke prevention Risk factor control Hypertension Cigarette smoking Dyslipidemia Diabetes mellitus Alcohol consumption Abdominal obesity and nutrition Physical inactivity Antithrombotic therapy

37 (Gilbert JM et al., Top Antivir Med 2015)

38 (Van Matre ET et al., Vasc Health Risk Manag 2016)

39 Conclusions Increasing incidence of cerebrovascular diseases in HIV-infected people Primary role of traditional cardiovascular risk factors Contribution of HIV and chronic inflammation Effect of specific antiretroviral drugs on vascular disease Association between cerebrovascular disease and neurocognitive disorders (mainly driven by cardiovascular risk factors) Risk factor control is mandatory

HIV AND CEREBROVASCULAR DISEASE: AN INTERSECTION OF EPIDEMICS

HIV AND CEREBROVASCULAR DISEASE: AN INTERSECTION OF EPIDEMICS Felicia C. Chow, MD, MAS University of California, San Francisco Departments of Neurology and Medicine (Infectious Diseases) September 26,