NORTHWEST AIDS EDUCATION AND TRAINING CENTER Heart Disease in the HIV+

NORTHWEST AIDS EDUCATION AND TRAINING CENTER Heart Disease in the HIV Person Ted Gibbons, MD January 15, 2015 Section Chief, Cardiology Harborview Medical Center University of Washington School of Medicine [email protected]

Outline CORONARY ARTERY DISEASE MYOCARDIAL AND PERICARDIAL DISEASE PULMONARY HYPERTENSION ATRIAL FIBRILLATION

CORONARY ARTERY DISEASE The Spectrum of CAD in HIV Persons North America: 15% of deaths in HIV population due to CV dz Severity spectrum: typically present with Acute Coronary Syndromes, but also subject to silent ischemia, stable angina and SCD Typical patient: - Young man, mean age 48 years old 8 years of HIV disease On ART (53-96% of reported series, 59% on PI) Often a smoker (45%) With Dyslipidemia (17-58%) ACS Diagnosis: - STEMI 29-64% (AN EXCESS) NSTEMI 20-48% Unstable angina 18-46% Male 81-97% PCI, CABG efficacy is similar to non-HIV population Mortality is similar for equivalent disease burden ACS recurrence is substantially higher with HIV (HR 6.5): Lipids/HIV Boccara F et al. J Am Coll Cardiol 2013;61:511–23 (systematic review) Collaborative analysis of 13 HIV cohort studies. Clin Infect Dis 2010;50:1387–96.

CORONARY ARTERY DISEASE MI Risk is Higher at Every Age of HIV RR for CAD: 2.8--3.0 women 1.4—2.1 men .but incomplete data on smoking Triant VA JID 2012:205 (Suppl 3): S355-361 Triant VA et al. J Clin Endocrinol Metab 2007; 92: 2506–2512 AIDS 2010;24:1228 –30

CORONARY ARTERY DISEASE Profile in HIV Persons: CAD Risk Risk for STEMI NSTEMI c/w general population Boccara F et al. J Am Coll Cardiol 2013;61:511–23

CORONARY ARTERY DISEASE Pathophysiology of CAD in ART Era Traditional CAD Risk Factors - Age Smoking (2.5 x risk of non-HIV ) Hypertension ( in ART) Atherogenic Dyslipidemia ( in some aRT) - Cf Dr Subramanian talk Inflammatory state Procoagulant state Immune activation within atherosclerotic plaque Vascular endothelial dysfunction Enhanced CHD Risk with ART interruption Boccara F et al. J Am Coll Cardiol 2013;61:511–23

CORONARY ARTERY DISEASE “Cardiometabolic Risk” Brunzell JD et al. , Diabetes Care 31:811-822, 2008

CORONARY ARTERY DISEASE Lipids: Age, Seroconversion and ART Therapy Lipid Profiles (mean values) Pre and Post-Seroconversion and after HAART Initiation in MEN TC HDL LDL 250 200 150 100 50 0 Lipid Fraction (mg/dL) Pr er s e o oc n n io s r ve m (ti e0 n ea ,m a Tim 3 ge 5 yr fo e eB s) H re R AA 7 T( .8 ar ye s) e1 Tim HA (9 T AR .1 ) rs a ye e2 Tim HA (9 T AR .6 ) rs a ye Tim e3 HA T( R A . 11 7 ar ye Tim Time Point Adapted from data in Riddler SA et al. JAMA 2003; 299:2978-2982 (MACS data) e4 s) HA T( R A . 12 2 ar ye s)

CORONARY ARTERY DISEASE CAD Risk-Equivalent Conditions Coronary Artery Disease Diabetes mellitus II Abdominal Aortic Aneurysm Symptomatic Carotid disease or 50% CCA stenos Peripheral arterial disease Framingham Score 20% 10 yr risk CACS 75th pctl Chronic Renal Disease, GFR 59 ml/min/1.73M2 HIV NCEP Guidelines Circulation 110:227, 2004

CORONARY ARTERY DISEASE Is HIV Status a CAD Risk Equivalent? Average Baseline risk HIV risk 16.4% x (1.4-2.0) 23-35% Treatment recommended regardless of HIV status: highly dependent on age and other RF http://tools.cardiosource.org/ASCVD-Risk-Estimator/

CORONARY ARTERY DISEASE CHD Risk Workup in the HIV Person o o o o o o o o o o Smoking habits Diet Level of exercise activity Family history of coronary artery or vascular disease, hypertension, or diabetes mellitus Baseline blood pressure Waist circumference Body mass index Random lipid profile (fasting if TG 200 mg/dL) HbA1c, renal profile Consider Stress Testing for symptoms or markedly elevated risk* Fihn SD et al. SIHD Guideline . J Am Coll Cardiol 2012;60:e44–164; 2014 Update*

CORONARY ARTERY DISEASE Initial Treatment of CAD-I Fihn SD et al. SIHD Guideline . J Am Coll Cardiol 2012;60:e44–164; 2014 Update

CORONARY ARTERY DISEASE Initial Treatment of CAD-II Rx Symptoms Rx Risk Fihn SD et al. SIHD Guideline . J Am Coll Cardiol 2012;60:e44–164; 2014 Update

CORONARY ARTERY DISEASE Guidelines 2013: 4 Statin Benefit Groups Clinical ASCVD* LDL-C 190 mg/dL, Age 21 years Primary prevention : Diabetes: Age 40-75 years, LDL-C 70-189 mg/dL Primary prevention: No Diabetes†: 7.5%‡ 10-year ASCVD risk, Age 40-75 years, LDL-C 70-189 mg/dL http://circ.ahajournals.org/lookup/doi/10.1161/01.cir.0000437738.63853.7a

CORONARY ARTERY DISEASE Individuals Not in a Statin Benefit Group In those for whom a risk decision is uncertain, these factors may inform clinical decision making: Family history of premature ASCVD Elevated lifetime risk of ASCVD LDL-C 160 mg/dL hs-CRP 2.0 mg/L CAC score 300 Agatston units ABI 0.9 This may sound familiar as “Enhanced Risk” from ATP III update Statin use still requires discussion between clinician and patient http://circ.ahajournals.org/lookup/doi/10.1161/01.cir.0000437738.63853.7a

CORONARY ARTERY DISEASE Statin Treatment Goals ªHigh-intensity statin therapy is defined as a daily dose that lowers LDL-C by 50% and ªModerate-intensity by 30% to 50%. ªAll patients with ASCVD who are age 75 years, as well as patients 75 years, should receive high-intensity statin therapy ªIf not a candidate for high-intensity, should receive moderate-intensity statin therapy. ªFollow-Up LDL/AST in 6-8 weeks http://circ.ahajournals.org/lookup/doi/10.1161/01.cir.0000437738.63853.7a Boccara F et al. J Am Coll Cardiol 2013;61:511–23

Myocardial Disease Systolic Dysfunction Pre-ART and On ART Focal myocarditis may be seen on bx or MRI regardless of ART Cardiotropic viruses implicated Symptomatic cardiomyopathy still only 1-3% in pre-ART era In ART-limited areas (South Africa), up to 38% of new heart failure has been attributed to HIV-associated cardiomyopathy Etiologies proposed: Inflammatory cytokines in HIV Coxsackievirus, Cytomegalovirus, EpsteinBarr virus Cryptococcus neoformans and toxoplasma (CD4 200 cells/mm Illicit drugs: alcohol; cocaine and methamphetamine may be synergistic with infectious agents Pentamidine, zidovudine Symptoms and treatment are similar to non-HIV associated myocardial disease Cardiac Tumors (Kaposi and non-Hodgkin lymphomas) Autonomic Dysfunction (tachycardia, prolonged QTc) Barbaro G et al. N Engl J Med. 1998;339(16):109 Ntsekhe M, Mayosi BM. Nat Clin Pract Cardiovasc Med 2009; 6:120.

Myocardial Disease Myocardial Disease: Systolic Dysfunction in ART Era Systematic review of 2,242 HIV minimally symptomatic Median age 42 years, 8.1 years of HIV diagnosis HAART in 98% Median CD4 489 cells/mm3 No Heart Failure (NYHA 1) 8.3% had LVEF 55% Predictors of LVSD: hcCRP 5 mg/L Active smoking Hx of MI Cerrato E et al. European Heart Journal (2013) 34, 1432–1436

Myocardial Disease Myocardial Disease: Diastolic Dysfunction in ART Era 43% had echo evidence of diastolic dysfunction: 32% grade I 8.5% grade II 3.0 % grade III Predictors of diastolic dysfunction: Age (OR 2.30) Hypertension (OR 2.5 per decade rise) Adapted from Ommen S R , Nishimura R A Heart 2003;89:iii18-iii23 Cerrato E et al. European Heart Journal (2013) 34, 1432–1436

PERICARDIAL DISEASE Pericardial Disease in HIV Asymptomatic pericardial effusions 10-40% in AIDS pre-ART era In symptomatic, myo-pericarditis commonly occurs (Africa), especially in In symptomatic patients, 2/3 are caused by infection or neoplasm; up to develop pericardial tamponade Etiologies: Mycobacteria: M. tuberculosis, M. aviumintracellulare, M. kansasii 42 90% of HIV pericardial effusion is M Tb in sub-Saharan Africa Staphylococcus aureus (11%) NH-Lymphoma and primary B-cell and Kaposi's sarcoma (15%) No etiology (26%) Rare fungals and others reported Rx is based on agent and need for intervention with pericardial drainage Prognosis related to agent and HIV state: 64% mortality at 6 months with AIDS vs 6% with no pericardial effusion Chen Y et al. Am Heart J 1999; 137:516 Mayosi BM Circulation. 2005;112:3608-3616. Syed FF et al. Heart 2014; 100:135.

PULMONARY HYPERTENSION Pulmonary Hypertension in HIV Disease Uncommon complication of HIV ( 1/200) Definition: Cath Mean PA pressure 25 with PCW 15 mm Hg Evaluate for other causes of PH: Hepatitis B and C Methamphetamine use L heart failure Intrinsic pulmonary disease Chronic thromboembolic disease ( in HIV disease also) Mixed etiologies (sarcoid/metabolic/heme/rheum) Etiology uncertain: HIV proteins suggested/arteriopathy Prognosis is poor with median survival 2-3 years Therapy is for symptomatic relief, modest effect on survival Combination ART PAH Therapy PAH Therapy: epoprostenol or bosentan-like drugs Ca channel blockers and sildenafil NOT recommended Mehta NJ et al. Chest 2000; 118:1133 Degano B et al. Eur Respir J. 2009;33:9 Zuber JP et al. Clin Infect Dis 2004; 38:1178 Simonneau G et al. J Am Coll Cardiol 2013; 62:S34

ATRIAL FIBRILLATION Atrial Fibrillation/Flutter and HIV Disease Unclear if CHADS2-Vasc is valid assessment of CVA Risk with HIV Multivariate Predictors of AF: Lower CD4 count ( 200 cells/mm3 Higher viral load (100,000 copies/ml) Older age White Race CAD CHF CKD, proteinuria Hypothyroidism Alcoholism 50% higher than historical age groups, more AA Hsu JC et al. J Am Coll Cardiol 2013;61:2288–95 (VA cohort of 30, 543 HIV Veterans)

WRAP-UP Summary: Cardiac Disease with HIV CAD risk is similar to that of family history of premature MI Comorbidities enhance risk in many with HIV Modifiable risk factors include smoking, dyslipidemia, obesit hypertension, illicit drug use, excess alcohol and sedentary lifestyle Standard EBM approaches to CAD risk reduction apply, with important adjustments for ART drug interactions Myocardial, pericardial disease and venous thromboembolis have receded as important HIV-specific complications in developed countries, but remain important complication with CD4 counts 200 cells/mL Atrial fibrillation is an emerging cardiovascular threat in the aging and younger HIV population

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