Managing Cardiovascular Risk in HIV A Toolkit for HIV Clinicians CVD Risk and Assessment Smoking Cessation Counselling Management of Lipids Management of Diabetes Management of Hypertension Management of KidneyDisease
Disclosure of Potential for Conflict of Interest Marek Smieja, MD PhD FRCPC Cardiovascular Risk in HIV: A Toolkit for HIV Clinicians program FINANCIAL DISCLOSURE Speakers Bureau/Honoraria (100% donated): Abbott, Astra-Zeneca, BI, BMS, GSK/Viiv, Merck, Pfizer, Roche, Tibotec Grants: Pfizer (Champix), Gilead (Canadian HIV Vascular Study)
“There needs to be recognition among both HIV clinicians and cardiologists that first, these patients are at risk for cardiovascular disease and, second, we need to recognize that risk and figure out what we need to do to treat it." Grinspoon SK, et al. Circulation 2008;118:198-210.
Objectives • This CME course is designed to provide the HIV clinician with: • the tools needed for recognition of the various factors that lead to increased cardiovascular (CV) risk in HIV • the knowledge required for the diagnosis of the factors that lead to increased CV risk in HIV • the guidelines for the management of the factors that lead to increased CV risk in HIV CME: continuing medical education
Overview CVD Risk and Assessment Smoking Cessation Counselling Management of Lipids Management of Diabetes Management of Hypertension Management of Kidney Disease
Program Development Committee • Co-chairs: Anita Rachlis • Marek Smieja • Committee: Linda Robinson • Jean-Guy Baril • Greg Bondy • Julian Falutz • Marianne Harris • Mona Loutfy • Alireza Zahirieh
CVD Risk Factors in the HIV Population hs-CRP? Lipids* Inactivity, Diet Gender Abdominal Obesity* Age CVD Risk Cigarette Smoking Family History - - Hyper-tension* HIV Infection Hyper-glycemia* Insulin Resistance ARV Orange = Modifiable Green = Non-modifiable Purple = HIV-associated Diabetes *Metabolic syndrome ARV: antiretroviral therapy; hs-CRP: high-sensitivity C-reactive protein Adapted from Carr A. Clinical Care Options HIV. Available at: www.clinicaloptions.com/hiv
Canadian Evidence-BasedGuidelines on CV Risk in HIV Primary Authors: Marek Smieja Astha Ramaiya Greg Bondy CV Experts:Jacques Genest Allan Sniderman Working Group: Jean-Guy Baril Julian Falutz Marianne Harris Sean Hosein Mona Loutfy Anita Rachlis Linda Robinson
The Guideline Panel Asked the Following Questions… • Does HIV infection contribute to CV risk? • Do traditional factors associated with increased CV risk have the same impact in HIV patients? • Does HAART contribute to CV risk in HIV? • Are traditional screening methods applicable in HIV? • Are traditional CV risk management strategies applicable in HIV? HAART: highly active antiretroviral therapy
Quality of the Evidence Grade I: RCT or meta-analysis Grade II: Observational data II-a. Prospective cohort study II-b: Retrospective cohort or administrative database II-c: Case-control Grade III: Expert opinion, clinical experience, descriptive studies Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
Strength of Recommendation Category A: Strong evidence to support Category B: Moderate evidence to support Grade C: Poor evidence to support or recommend Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
Summary Does HIV infection contribute to CV risk? HIV is a weak cardiac risk factor (B-II) Do traditional factors associated with increased CV risk have the same impact in HIV patients? HIV patients: high smoking (A-II), other factors (B-ll) Does HAART contribute to CV risk in HIV? HAART: PI (B-II) > NRTI (C-II) > NNRTI Starting & stopping HAART (B-II) Are traditional screening methods applicable in HIV? Screening: Framingham (B-II) + time on HAART (C-II) Are traditional CV risk management strategies applicable in HIV? Treatment: statins (A-I); switching ARVs (B-I); smoking cessation medications (A-I) HAART: highly active antiretroviral therapy; ARVs: antiretrovirals; PI: protease inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
Screening for all patients: ART: antiretroviral therapy; EtOH: ethyl alcohol; BMI: body mass index; BP: blood pressure; TC: total cholesterol; HDL-C: high-density lipoproteincholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglycerides; eGFR: estimated glomerular filtration rate * More frequent monitoring if patient is in the process of lifestyle modification and/or starting or adjusting new medications for hypertension, hyperglycemia, or hyperlipidemia. Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
Framingham Risk Score Used to Estimate 10-Year CV Risk Developed for use in general population Thought to be reasonable predictor in HIV-infected population However, does not include HIV-specific factors Immune status Increased inflammatory markers Insulin resistance Time on HAART Calgary Health Region online risk calculator. Available at: http://www.calgaryhealthregion.ca/healthinfo/tools/heart_health.htm
Treatment of Increased CV Risk Smoking cessation counselling and medications Manage lipids Lifestyle modifications: exercise, diet Pharmaceutical management to meet lipid targets based on risk stratification Treat hypertension and diabetes as per current guidelines Treat underlying CV disease Prevent CV disease in high-risk populations Maintain healthy renal function Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
Useful Links and Resources On-line risk calculator (Canadian) http://www.calgaryhealthregion.ca/healthinfo/tools/heart_health.htm Infectious Diseases Society of America (IDSA)Guidelines for Managing CV Risk in HIV http://www.idsociety.org/Content.aspx?id=5912 European AIDS Clinical Society (EACS)Guidelines http://www.europeanaidsclinicalsociety.org/guidelines.asp
Overview CVD Risk and Assessment Smoking Cessation Counselling Management of Lipids Management of Diabetes Management of Hypertension Management of Kidney Disease
What are the effects of nicotine? Why do people continue to smoke? PHYSICALDEPENDENCE Drop in nicotine levels leads to craving and withdrawal Tobacco Dependence is a Medical Condition Smoking prevalence: General population: 20% HIV population: 40-70% Heishman SJ. Nicotine Tob Res 1999;1(Suppl 2):S143-7.
The 5A’s Model Further information on this model available at: http://ctica.org
Is he/she currently smoking? Has he/sheconsidered quitting? Would he/she like your help to quit? Yes Yes Yes No No No Discuss smoking cessation or arrangean appointment to address next steps in strategy1 Make note in file and address at future appointments Make note in file and offer assistance when patient is ready Make note in file and address at future appointments ASK…(at every visit) Hughes JR, et al. Cochrane Database Syst Rev 2005;2:CD001007; Jorenby DE, et al. JAMA 2006;296:56-63; Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;2:CD001292; Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;3:CD001118; Silagy C, et al. Cochrane Database Syst Rev 2004;3:CD000146; Stead LF, et al. Cochrane Database Syst Rev 2005;3:CD002850.
ADVISE… Offer advice on quitting using messages that are… • CLEAR “I think it is important for you to quit smoking now, and I can help you.” • STRONG “As your clinician, I need you to know that quitting smoking is very important to protecting your health now and in the future.” • PERSONALIZED Link tobacco use to health/illness (reason for office visit), social/economic costs, motivation level and impact on others (e.g., children) Fiore MC, et al. US Department of Health and Human Services. Public Health Service; 2008. Available at: www.surgeongeneral.gov/tobacco/default.htm
ASSESS….. A patient’s readiness to quit can be anywhere from “no way” to “I’m ready” and anywhere in between Stages of Behaviour Change Pre-contemplation-Contemplation-Preparation-Action-Maintenance Knowledge Skills Changes in Attitude Enablers Reward System Reinforcements The healthcare provider focuses their efforts and education to best motivate the patient to move across this continuum to the right Prochaska JO, DiClemente CC. In: Norcross JC, Goldfried MR (eds). Handbook of psychotherapy integration 2nd ed. Oxford University Press; 2005.
ASSIST… Three strategies have been proven to help patients quit smoking: • Set a QUIT DATE • Behavioural therapies to help patients recognize and adapt to TRIGGERS • MEDICATIONS Hughes JR. CA Cancer J Clin 2000;50:143-51.
Most Common Medications Hughes JR, et al. Cochrane Database Syst Rev 2004;4:CD000031; Jorenby DE, et al. JAMA 2006;296:56-63; Silagy C, et al. Cochrane Database Syst Rev 2004;3:CD000146. Hesse LM, et al. Drug Metab Dispos 2001;29:100-102.
ARRANGE… • Follow-up contact should begin soon after the quit date, preferably during the first week. • A second follow-up contact is recommended within the first month. • Schedule further follow-up contacts as indicated. • For patients who are abstinent, congratulate them on their success. • Assess problems and anticipate challenges in the immediate future. • Assess medication use and problems. • Remind patients of quit support mechanisms. • Address tobacco use at next clinical visit (treat tobacco use as a chronic disease). • If tobacco use has occurred, review circumstances and elicit recommitment to total abstinence. US Department of Health and Human Services. Available at: www.surgeongeneral.gov/tobacco/default.htm (accessed Aug. 17, 2009)
Useful Links and Resources Flow Sheet for Chart www.ctica.org/cessation/cessation.html “downloads” Smoker’s Helpline: 1-877-513-5333www.smokershelpline.ca Guidelines from the US Department of Health and Human Services, Office of the Surgeon General Ministry of Health Promotionwww.mhp.gov.on.ca/english/health/smoke_free/default.asp Physicians for a Smoke-Free Canada www.smoke-free.ca
Screen fasting lipid profile in… • Men ≥ 40 years, women ≥ 50 years or postmenopausal • All adults with any of the following, regardless of age: • Diabetes • Cigarette smoking • Hypertension • Obesity (BMI > 27 kg/m2) • Family history of premature CAD • Clinical signs of hyperlipidemia • Evidence of atherosclerosis • Rheumatoid arthritis, systemic lupus erythematosis, psoriasis • HIV infection on HAART • eGFR < 60 mL/min/1.73 m2 • Erectile dysfunction • Screen children with a family history of hypercholesterolemia or chylomicronemia BMI: body mass index; CAD: coronary artery disease; eGFR: estimated glomerular filtration rate; HAART: highly-active antiretroviral therapy Genest J. et al. Can J. Cardiol 2009;25:567-79.
Obtain Fasting Lipids and Apo-B (if possible)** • Baseline • Prior to starting HAART • 3-6 months after HAART initiation • Yearly (re-assess risk q12 months) • Calculate & Categorize • CV Risk • Calculate using Framingham • <10% = LOW RISK • 10%- 19% = MODERATE RISK • >20% = HIGH RISK • Consider calculating Reynolds Risk • Score (if hs-CRP assessed) • Assess Co-morbidities* • Diabetes mellitus • Coronary heart disease • Previous CV event • Atherosclerosis • Aneurysm • *ANY = HIGH RISK • Determine Lipid Targets • LOW RISK: ≥ 50% ↓ LDL-C • MODERATE: LDL-C<2.0 or • ≥ 50% ↓ LDL-C or apo-B<0.8 • HIGH RISK: LDL-C<2.0 or • ≥ 50% ↓ LDL-C or apo-B<0.8 ** Evidence suggests that apolipoprotein-B (apo-B) is a better marker of vascular disease risk and provides a better index of the adequacy of lipid-lowering therapy than LDL-C. Also, there appears to be less laboratory error with apo-B. It is particularly useful in cases where it is not possible or convenient to get “fasting” lab results. First Steps to Managing Lipids TREAT TO TARGET • Adapted from Genest J, et al. Can J Cardiol 2009;25:567-79.
TREAT TO TARGET Low-to-Moderate Risk High-risk Start with… Lifestyle Interventions + Pharmacological Management If lipid targets are not met with 3- to 6-month trial… Pharmaceutical Management • Lipid-Lowering Therapy • Start with low-dose statin for LDL-C • Increase dose to effect or ADR • Add ezetimibe if not at target • Fibrates for TGs to avert pancreatitis • Altering ARV Therapy • Consider ritonavir-sparing/PI switching • Consider switching PI to NNRTI • Consider nuke switching or sparing • Consider newer agents and/or Reassess CV risk category and targets 3-6 months after pharmaceutical intervention then yearly once targets are met • Lifestyle Interventions: • Dietician consultation (reduced saturated fats/sugars) • Smoking cessation consultation • Weight reduction and maintenance • Exercise (daily); at least 30 min/day
When to Treat **Double the risk if a first generation relative has suffered a CV event prior to the age of 60 Genest J, et al. Can J Cardiol 2009;25:567-79.
Target Lipid Levels *Secondary (optional targets) once LDL-C at goal: TC:HDL-C < 4.0 Non-HDL-C < 3.5 mmol/L TG < 1.7 mmol/L Apo-B:Apo-AI < 0.80 hs-CRP < 2 mg/L CAD: coronary artery disease; PVD: peripheral vascular disease; RRS: Reynolds Risk Score Adapted from Genest J, et al. Can J Cardiol 2009;25:567-79.
Lipid-Lowering Agents and PIs: Drug Interactions Fenofibrate Fluvastatin Ezetimibe Fish oil Low interaction potential Statin + fibrate Atorvastatin Rosuvastatin Pravastatin* Niacin Gemfibrozil Use cautiously: “START LOW-GO SLOW “ http://www.hivclinic.ca/main/drugs_interact_files/LIPID-drugs.pdf Lovastatin Simvastatin Contraindicated *Area under the curve (AUC) ↑↑↑ with darunavir. Adapted from Fichtenbaum CJ, et al. AIDS 2002;16:569-577; Hsyu PH, et al. Antimicrob Agents Chemother 2001;45:3445-50; Gerber JG, et al. IAS 2003. Abstract 870; Carr RA, et al.ICAAC 2000. Abstract 1644; Telzir Package Insert 2003; Gerber JG, et al. CROI 2004. Abstract 603; Reyataz Package Insert 2005; Aptivus Product Label 2005.
Summary: Switching ARVs Switching ARVs is an appropriate strategy to manage dyslipidemia for some patients Maintaining virologic control is of paramount importance Must consider treatment history, resistance mutations present Potency of new regimen must be adequate
Useful Links and Resources On-line risk calculator (Canadian) http://www.calgaryhealthregion.ca/healthinfo/tools/heart_health.htm Infectious Diseases Society of America (IDSA)Guidelines for Managing CV Risk in HIV http://www.idsociety.org/Content.aspx?id=5912 European AIDS Clinical Society (EACS)Guidelines http://www.europeanaidsclinicalsociety.org/guidelines.asp Toronto General Hospital HIV Clinic – Drug Interaction Tables http://www.hivclinic.ca/main/drugs_interact.html(see Lipid-lowering drugs)
Diabetes Risk Factors • HIV-associated DM • Risk Factors • Peripheral lipoatrophy • Reduced adiponectin • Increased liver/muscle fat • Inflammatory cytokines • Low testosterone • HCV co-infection • Protease inhibitors, d4T • Classical DM • Risk Factors • Abdominal obesity • Physical inactivity • Genetic • Family history • Race/ethnicity • Older age • Dyslipidemia InsulinResistance DM: diabetes mellitus; HCV: hepatitis C virus; d4T: stavudine Adapted from Dube MP. Clinical Care Options. Available at: www.clinicaloptions.com/HIV/Management Series/Insulin Resistance/Modules/Dube.aspx
Diagnosis of Diabetes 6.1-6.9 mmol/L FPG ≥ 7.0 mmol/L Confirmedby any of these 3 laboratory tests on another day OR Casual PG > 11.1 mmol/L with symptoms of polydipsia or polyuria or unexplained weight loss AND/OR OR 7.8-11.1 mmol/L 2h PG in a 75-g OGTT > 11.1 mmol/L IFG and/orIGT DIABETES FPG: fasting plasma glucose; PG: plasma glucose; OGTT: oral glucose tolerance test; IFG: impaired fasting glucose; IGT: impaired glucose tolerance Adapted from Canadian Diabetes Association. Can J Diabetes 2008;32(Suppl 1):S1-S201.
Lifestyle intervention: nutrition therapy and physical activity (initiate this step at first signs of IFG,IGT or metabolic syndrome) A1C > 7.0%: Add Metformin and titrate dose to maximum 1 g BID if tolerated (consider sooner for A1C > 9.0%) A1C > 7.0%: Add 1 or more sequentially Alpha-glucosidase inhibitor i.e., acarbose Incretin DDP-4 inhibitor i.e. sitagliptin Secretagogue i.e., glicazide, glyburide TZD i.e., pioglitazone **AVOID in CHF Insulin: sooner for A1C > 9.0% or metabolic syndrome Management of Diabetes DIABETES Adapted from Canadian Diabetes Association. Can J Diabetes 2008;32(Suppl 1):S1-S201.
Targets For Treatment Canadian Diabetes Association. Can J Diabetes 2008;32(Suppl 1):S1-S201.
Useful Links and Resources Diabetes Management and Assessment Flow Sheet http://www.sgfp.ca/forms.html CDA Diabetes Guidelines 2008 http://www.diabetes.ca/for-professionals/resources/2008-cpg/ “download”- Appendix 2 sample flow sheet p.S195 Toronto General Hospital HIV Clinic Drug Interaction Tables http://www.hivclinic.ca/main/drugs_interact.html (see Oral hypoglycemics)
Hypertensive Urgency/ Emergency BP >140/90 mmHg and TargetOrgan Damage or Diabetes or Chronic Kidney Disease or BP >180/110? Diagnosis of HTN Yes No BP: 140-179 /90-109 mm Hg Diagnosis of Hypertension Elevated Out ofthe Office BPMeasurement Elevated RandomOffice BPMeasurement Hypertension Visit 1 BP Measurement, History and Physical Examination Diagnostic tests ordering at visit 1 or 2 Hypertension Visit 2 within 1 month Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Clinic BP ABPM (if available) Home BPM Hypertension Visit 3 ≥160 SBP or ≥100 DBP <160 / 100 Hypertension Visits 4-5 ≥140 SBP or ≥90 DBP <140 / 90 Awake BP <135/85 and 24-hour <130/80 Awake BP ≥135 SBP or ≥ 85 DBP or 24-hour ≥130 SBP or ≥80 DBP <135/85 ≥135/85 Diagnosisof HTN ABPM orHBPM or or Diagnosisof HTN Continue tofollow-up Continue tofollow-up Diagnosisof HTN Continue tofollow-up Diagnosisof HTN Diagnosis of Hypertension (cont’d) BP: 140-179 / 90-109 mm Hg Patients with high normal blood pressure (clinic SBP 130-139 and/or DBP 85-89) should be followed annually. ABPM: ambulatory blood pressure monitoring (please see back-up slides for more information on ABPM). Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
When to Treat ≥ 2 consecutive measures ≥ thresholds = TREAT SBP: systolic blood pressure; DBP: diastolic blood pressure Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Goals of Therapy Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
How to Treat TARGET <140/90 mm Hg (<130/80 mm Hg in diabetes or CKD) Lifestyle modification A combination of 2 first-line drugs may be considered as initial therapy if BP is >20 mm Hg systolic or >10 mm Hg diastolic above target Initial therapy Thiazide diuretic ACE-I ARB Long-acting CCB Beta blocker* • CONSIDER: • Non-adherence • Secondary HTN • Interfering drugs • or lifestyle • White coat effect Dual combination Triple or quadruple therapy *Not indicated as first-line therapy > 60 years. ACE-I: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CCB: calcium-channel blocker; HTN: hypertension Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Lifestyle Therapies DASH: Dietary Approaches to Stop Hypertension; BMI: body mass index *DASH diet emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fiber, whole grains and protein from plant sources that is reduced in saturated fat and cholesterol. Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009