Post on 19-Dec-2015
Managing Cardiovascular Risk in HIV
A Toolkit for HIV Clinicians
Management of
Lipids
Management of
Diabetes
Smoking Cessation
Counselling
CVD Risk and Assessment
Management of KidneyDisease
Managementof
Hypertension
Disclosure of Potential for Conflict of Interest
Marek Smieja, MD PhD FRCPCCardiovascular 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
Management of Lipids
Management of Diabetes
Smoking Cessation Counselling
CVD Risk and Assessment
Management of Kidney Disease
Management of Hypertension
Overview
Program Development Committee
Co-chairs: Anita RachlisMarek Smieja
Committee: Linda RobinsonJean-Guy BarilGreg BondyJulian FalutzMarianne HarrisMona LoutfyAlireza Zahirieh
CVD Risk and Assessment
CVD Risk and Assessment
HIV Infection
ARV
*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
CVD Risk Factors in the CVD Risk Factors in the HIV PopulationHIV Population
Gender
CVD Risk
--
Diabetes
Lipids*
Family History
Abdominal Obesity*
Hyper-tension*
Cigarette Smoking
Hyper-glycemia*
Insulin Resistanc
e
Inactivity, Diet
Age
Orange = ModifiableGreen = Non-modifiablePurple = HIV-associated
hs-CRP?
Canadian Evidence-BasedGuidelines on CV Risk in HIV
Primary Authors: Marek SmiejaAstha RamaiyaAstha RamaiyaGreg BondyGreg Bondy
CV Experts: Jacques GenestJacques GenestAllan SnidermanAllan Sniderman
Working Group: Jean-Guy BarilJulian FalutzMarianne HarrisSean HoseinMona LoutfyAnita RachlisLinda Robinson
The Guideline Panel Asked the Following Questions…
1) Does HIV infection contribute to CV risk?
2) Do traditional factors associated with increased CV risk have the same impact in HIV patients?
3) Does HAART contribute to CV risk in HIV?
4) Are traditional screening methods applicable in HIV?
5) Are traditional CV risk management strategies applicable in HIV?
HAART: highly active antiretroviral therapy
Quality of the Evidence
• Grade I: RCT or meta-analysisRCT or meta-analysis
• Grade II: Observational dataObservational data– II-a. Prospective cohort studyII-a. Prospective cohort study– II-b: Retrospective cohort or administrative II-b: Retrospective cohort or administrative
databasedatabase– II-c: Case-controlII-c: Case-control
• Grade III: Expert opinion, clinical experience,Expert opinion, clinical experience,descriptive studiesdescriptive 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
1) Does HIV infection contribute to CV risk?– HIV is a weak cardiac risk factor (B-II)
2) 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)
3) Does HAART contribute to CV risk in HIV?– HAART: PI (B-II) > NRTI (C-II) > NNRTI– Starting & stopping HAART (B-II)
4) Are traditional screening methods applicable in HIV?– Screening: Framingham (B-II) + time on HAART (C-II)
5) Are traditional CV risk management strategies applicable in HIV?– Treatment: statins (A-I); switching ARVs (B-I); smoking cessation
medications (A-I)
Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
HAART: highly active antiretroviral therapy; ARVs: antiretrovirals; PI: protease inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor
Screening for all patients:
Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
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.
Assessment How often?History• Personal or family history of CVD,
hypertension, diabetes• Personal habits: smoking, exercise, EtOH
• Family history at baseline, then update• Personal history, baseline, before ART, then
annually*
Physical• Weight, BMI, waist circumference, BP • Baseline, before ART, then annually*
Laboratory **• Fasting TC, HDL-C, LDL-C, TG, (apoB)• Fasting glucose, creatinine
• Consider hs-CRP
• Baseline, before ART, 3-6 months after starting ART, then annually*
Calculations• Framingham CV risk assessment• Consider Reynolds Risk Score (if
moderate risk)• Creatinine clearance, (eGFR)***
• Before ART and annually on ART• Baseline, annually in men > 45 yrs, women >
55 yrs
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 Smoking cessation counselling and medications
• Manage lipids Manage lipids
– Lifestyle modifications: exercise, diet Lifestyle modifications: exercise, diet
– Pharmaceutical management to meet lipid targets based on Pharmaceutical management to meet lipid targets based on risk stratificationrisk stratification
• Treat hypertension and diabetes as per current guidelinesTreat hypertension and diabetes as per current guidelines
• Treat underlying CV diseaseTreat underlying CV disease
• Prevent CV disease in high-risk populationsPrevent CV disease in high-risk populations
• Maintain healthy renal functionMaintain 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
Management of Lipids
Management of Diabetes
Smoking Cessation Counselling
CVD Risk and Assessment
Management of Kidney Disease
Management of Hypertension
Overview
Smoking Cessation Counselling
Smoking Cessation Counselling
Tobacco Dependence is a Medical Condition
Heishman SJ. Nicotine Tob Res 1999;1(Suppl 2):S143-7.
PHYSICALDEPENDENCEPHYSICALDEPENDENCE
What are the effects of nicotine?
Why do people continue to smoke?
Drop in nicotine levels leads to craving and withdrawal
Drop in nicotine levels leads to craving and withdrawal
Smoking prevalence: General population: 20%HIV population: 40-70%
The 5A’s Model
Further information on this model available at: http://ctica.org
ASK: Patients about smoking status at every visit
ADVISE:Patients about the health risks of tobacco use and to quit
ASSESS: Patients’ readiness to quit
ASSIST: Patients that are ready to quit
ARRANGE: Follow-up
ASK…(at every visit)
Is he/she currently smoking?
Has he/sheconsidered quitting?
Would he/she like your help to quit?
Make note in file and address at future appointments
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 offer assistance when patient is ready
Make note in file and address at future appointments
Make note in file and address at future appointments
Discuss smoking cessation or arrange an appointment to address next steps in strategy1
Discuss smoking cessation or arrange an appointment to address next steps in strategy1
NoNo
YesYes YesYesYesYes
NoNoNoNo
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…..
Pre-contemplation-Contemplation-Preparation-Action-MaintenancePre-contemplation-Contemplation-Preparation-Action-Maintenance
Stages of Behaviour Change
The healthcare provider focuses their efforts and education to best motivate the patient to
move across this continuum to the right
A patient’s readiness to quit can be anywhere from “no way” to “I’m ready” and anywhere in between
KnowledgeSkillsChanges in Attitude
KnowledgeSkillsChanges in Attitude
EnablersReward SystemReinforcements
EnablersReward SystemReinforcements
Prochaska JO, DiClemente CC. In: Norcross JC, Goldfried MR (eds). Handbook of psychotherapy integration 2nd ed. Oxford University Press; 2005.
ASSIST…
Hughes JR. CA Cancer J Clin 2000;50:143-51.
Three strategies have been proven to help patients quit smoking:
1. Set a QUIT DATE
2. Behavioural therapies to help patients recognize and adapt to TRIGGERS
3. MEDICATIONS
Most Common Medications
Medication Nicotine gumNicotine
patchNicotine inhaler
Bupropion* Varenicline
Treatment length
1-3 months 8-12 weeks 12-24 weeks 7-12 weeks 12 weeks
Main side effects
• Upset stomach
• Hiccups
• Headache• Disturbed
sleep• Site rash
• Irritation of throat and nasal passages
• Sneezing• Coughing
• Insomnia• Nausea• Depression
Dosage 2 mg, 4 mg7 mg,
14 mg, 21 mg
6-12 cartridges per
day
150 to 300 mg/day
0.5 mg qd to 1 mg bid
*Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely.
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.
US Department of Health and Human Services. Available at: www.surgeongeneral.gov/tobacco/default.htm (accessed Aug. 17, 2009)
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.
Flow Sheet for Chartwww.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 Promotion www.mhp.gov.on.ca/english/health/smoke_free/default.asp
Physicians for a Smoke-Free Canadawww.smoke-free.ca
Useful Links and Resources
Management of Lipids
Management of Lipids
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 therapyGenest J. et al. Can J. Cardiol 2009;25:567-79.
First Steps to Managing Lipids
** 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.
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)
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)
TREAT TO TARGETTREAT TO TARGET
Adapted from Genest J, et al. Can J Cardiol 2009;25:567-79.
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
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
Assess Co-morbidities*
• Diabetes mellitus• Coronary heart disease• Previous CV event• Atherosclerosis• Aneurysm *ANY = HIGH RISK
Assess Co-morbidities*
• Diabetes mellitus• Coronary heart disease• Previous CV event• Atherosclerosis• Aneurysm *ANY = HIGH RISK
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)
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)
Lifestyle Interventions: • Dietician consultation (reduced saturated fats/sugars)• Smoking cessation consultation• Weight reduction and maintenance• Exercise (daily); at least 30 min/day
Lifestyle Interventions: • Dietician consultation (reduced saturated fats/sugars)• Smoking cessation consultation• Weight reduction and maintenance• Exercise (daily); at least 30 min/day
Lifestyle Interventions + Pharmacological Management
Lifestyle Interventions + Pharmacological Management
Pharmaceutical ManagementPharmaceutical Management
and/or
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
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
Altering ARV Therapy• Consider ritonavir-sparing/PI switching• Consider switching PI to NNRTI• Consider nuke switching or sparing• Consider newer agents
Reassess CV risk category and targets 3-6 months after pharmaceutical intervention then yearly once targets are met
Reassess CV risk category and targets 3-6 months after pharmaceutical intervention then yearly once targets are met
If lipid targets are not met with 3- to 6-month trial…
TREAT TO TARGETTREAT TO TARGET
High-riskHigh-risk
Start with…
Low-to-Moderate RiskLow-to-Moderate Risk
When to Treat
**Double the risk if a first generation relative has suffered a CV event prior to the age of 60
Risk Level Initiate treatment if:High• CAD, PVD, atherosclerosis• Most patients with diabetes• Framingham: ≥20%• Reynolds Risk Sc. ≥ 20%
• Consider treatment in all patients
Moderate• Framingham: 10-19%
• LDL-C > 3.5 mmol/L• TC:HDL-C > 5.0• hs-CRP > 2 mg/L (in men > 50 yrs, women >
60 yrs)• Family history** and hs-CRP modulates
risk score (RRS)
Low• Framingham: < 10%
• LDL-C ≥ 5.0 mmol/L
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
Primary targets*
Risk Level LDL-C (mmol/L) Alternate: Apo-B (g/L)
High• CAD, PVD, atherosclerosis• Most patients with diabetes• Framingham: ≥ 20%• RRS: ≥ 20%
< 2.0 or ≥ 50% ↓ LDL-C
< 0.80
Moderate• Framingham: 10-19%
< 2.0 or ≥ 50% ↓ LDL-C
< 0.80
Low• Framingham: < 10% ≥ 50% ↓ LDL-C
—
Adapted from Genest J, et al. Can J Cardiol 2009;25:567-79.
Lipid-Lowering Agents and Lipid-Lowering Agents and PIs: Drug InteractionsPIs: Drug Interactions
FenofibrateFluvastatinEzetimibe
Fish oil
Use cautiously: Use cautiously: ““START LOW-GO SLOW “START LOW-GO SLOW “http://www.hivclinic.ca/main/drugs_interact_files/LIPID-drugs.pdf
Statin + fibrateAtorvastatinRosuvastatinPravastatin*
NiacinGemfibrozil
LovastatinSimvastatin
Contraindicated
Low interactionpotential
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.
*Area under the curve (AUC) ↑↑↑ with darunavir.
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 HIVhttp://www.idsociety.org/Content.aspx?id=5912
European AIDS Clinical Society (EACS) Guidelineshttp://www.europeanaidsclinicalsociety.org/guidelines.asp
Toronto General Hospital HIV Clinic – Drug Interaction Tableshttp://www.hivclinic.ca/main/drugs_interact.html (see Lipid-lowering drugs)
Management of Diabetes
Management of Diabetes
Diabetes Risk Factors
DM: diabetes mellitus; HCV: hepatitis C virus; d4T: stavudine
InsulinResistance
InsulinResistance
Classical DM Risk Factors
• Abdominal obesity
• Physical inactivity• Genetic
• Family history• Race/ethnicity
• Older age• Dyslipidemia
HIV-associated DM Risk Factors
• Peripheral lipoatrophy• Reduced adiponectin• Increased liver/muscle fat• Inflammatory cytokines• Low testosterone• HCV co-infection• Protease inhibitors, d4T
Adapted from Dube MP. Clinical Care Options.
Available at: www.clinicaloptions.com/HIV/Management Series/Insulin Resistance/Modules/Dube.aspx
Diagnosis of 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.
IFGand/or
IGT
IFGand/or
IGT
Casual PG > 11.1 mmol/L with symptoms of polydipsia or polyuria
or unexplained weight loss
Casual PG > 11.1 mmol/L with symptoms of polydipsia or polyuria
or unexplained weight loss
DIABETESDIABETES
2h PG in a 75-g OGTT > 11.1 mmol/L2h PG in a 75-g OGTT > 11.1 mmol/L
FPG ≥ 7.0 mmol/LFPG ≥ 7.0 mmol/L
OR
OR
Confirmedby any of these 3 laboratory tests on another day
Confirmedby any of these 3 laboratory tests on another day
6.1-6.9mmol/L6.1-6.9mmol/L
7.8-11.1mmol/L7.8-11.1mmol/L
AND/OR
Management of Diabetes
Adapted from Canadian Diabetes Association. Can J Diabetes 2008;32(Suppl 1):S1-S201.
DIABETESDIABETES
Insulin: sooner for A1C > 9.0% or metabolic
syndrome
Insulin: sooner for A1C > 9.0% or metabolic
syndrome
TZD i.e., pioglitazone
**AVOID in CHF
TZD i.e., pioglitazone
**AVOID in CHF
Secretagoguei.e., glicazide,
glyburide
Secretagoguei.e., glicazide,
glyburide
Incretin DDP-4
inhibitor i.e. sitagliptin
Incretin DDP-4
inhibitor i.e. sitagliptin
Alpha-glucosidase
inhibitor i.e., acarbose
Alpha-glucosidase
inhibitor i.e., acarbose
A1C > 7.0%: Add 1 or more sequentially
Metformin and titrate dose to maximum 1 g BID if tolerated (consider sooner for A1C > 9.0%)
Metformin and titrate dose to maximum 1 g BID if tolerated (consider sooner for A1C > 9.0%)
A1C > 7.0%: Add
Lifestyle intervention: nutrition therapy and physical activity(initiate this step at first signs of IFG,IGT or metabolic syndrome)
Lifestyle intervention: nutrition therapy and physical activity(initiate this step at first signs of IFG,IGT or metabolic syndrome)
Targets For Treatment
Canadian Diabetes Association. Can J Diabetes 2008;32(Suppl 1):S1-S201.
No evidence that targets for the HIV-infected population should differ from those for the HIV-uninfected population
Parameter Goal
Glycemic control
A1C, % (try to achieve target within 6-12 months) ≤ 7.0
FPG or pre-prandial PG (mmol/L) 4.0 – 7.0
2-hr post-prandial PG (mmol/L) 5.0 – 10.0
Blood pressure, mm Hg < 130/80
Lipids
Primary target: LDL-C (mmol/L) ≤ 2.0
Secondary target: TC/HDL-C ratio < 4.0
Useful Links and Resources
Diabetes Management and Assessment Flow Sheethttp://www.sgfp.ca/forms.html
CDA Diabetes Guidelines 2008http://www.diabetes.ca/for-professionals/resources/2008-cpg/ “download”- Appendix 2 sample flow sheet p.S195
Toronto General Hospital HIV Clinic Drug Interaction Tableshttp://www.hivclinic.ca/main/drugs_interact.html (see Oral hypoglycemics)
Management of HypertensionManagement
of Hypertension
Diagnosis of Hypertension
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Hypertension Visit 2within 1 month
Diagnostic tests ordering at visit 1 or 2
Elevated Out ofthe Office BPMeasurement
Elevated Out ofthe Office BPMeasurement
Elevated RandomOffice BP
Measurement
Elevated RandomOffice BP
Measurement
Hypertension Visit 1BP Measurement,
History and Physical Examination
Hypertension Visit 1BP Measurement,
History and Physical Examination
Yes
BP >140/90 mmHg and TargetOrgan Damage or Diabetes or Chronic Kidney Disease
or BP >180/110?
BP >140/90 mmHg and TargetOrgan Damage or Diabetes or Chronic Kidney Disease
or BP >180/110?
No
BP: 140-179 /90-109 mm HgBP: 140-179 /90-109 mm Hg
Diagnosisof HTN
Diagnosisof HTN
HypertensiveUrgency/
Emergency
HypertensiveUrgency/
Emergency
Diagnosis of Hypertension (cont’d)
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
BP: 140-179 / 90-109 mm HgBP: 140-179 / 90-109 mm Hg
Hypertension Visit 3≥160 SBP or≥100 DBP
<160 / 100
Hypertension Visits 4-5≥140 SBP or≥90 DBP
<140 / 90
Hypertension Visit 3≥160 SBP or≥100 DBP
<160 / 100
Hypertension Visits 4-5≥140 SBP or≥90 DBP
<140 / 90
Clinic BPClinic BP
or
Diagnosisof HTN
Diagnosisof HTN
ABPM orHBPM
ABPM orHBPM
Diagnosisof HTN
Diagnosisof HTN
Continue tofollow-up
Continue tofollow-up
ABPM (if available)ABPM (if available)
Awake BP<135/85
and24-hour<130/80
Awake BP<135/85
and24-hour<130/80
Awake BP≥135 SBP or≥ 85 DBP or
24-hour≥130 SBP or
≥80 DBP
Awake BP≥135 SBP or≥ 85 DBP or
24-hour≥130 SBP or
≥80 DBP
Continue tofollow-up
Continue tofollow-up
Diagnosisof HTN
Diagnosisof HTN
Home BPMHome BPM
<135/85<135/85 ≥135/85≥135/85
Continue tofollow-up
Continue tofollow-up
Diagnosisof HTN
Diagnosisof HTN
or
When to Treat
SBP: systolic blood pressure; DBP: diastolic blood pressure
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
≥ 2 consecutive measures ≥ thresholds = TREAT
Thresholds for Initiation of Antihypertensive Agents
Condition Initiation
SBP or DBP mm Hg
• Systolic or diastolic hypertension 140/90
• Diabetes• Chronic kidney disease
130/80
Goals of Therapy
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Target Values for Treatment of Hypertension
Condition Target
SBP and DBP mm Hg
Isolated systolic hypertension < 140
Systolic/diastolic hypertension• Systolic BP • Diastolic BP
< 140< 90
Diabetes or chronic kidney disease• Systolic • Diastolic
< 130< 80
How to Treat
ACE-I: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CCB: calcium-channel blocker; HTN: hypertensionAdapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Lifestyle modificationLifestyle modification
TARGET <140/90 mm Hg (<130/80 mm Hg in diabetes or CKD)
Beta blocker*
Beta blocker*
Long-acting CCB
Long-acting CCBARBARBACE-IACE-IThiazide
diureticThiazide diuretic
CONSIDER:• Non-adherence• Secondary HTN• Interfering drugs or lifestyle• White coat effect
CONSIDER:• Non-adherence• Secondary HTN• Interfering drugs or lifestyle• White coat effect
Dual combinationDual combination
Triple or quadruple therapy
Triple or quadruple therapy
Initial therapyInitial therapy
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
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
*Not indicated as first-line therapy > 60 years.
Lifestyle Therapies
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
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.
Intervention Target
Reduce foods with added sodium < 2300 mg/day
Weight loss BMI < 25 kg/m2
Alcohol restriction < 2 drinks/day
Physical activity 30-60 minutes 4-7 days/week
Dietary patterns DASH diet*
Smoking cessation Smoke free environment
Waist circumference- Europid- South Asian, Chinese
Men Women < 94 cm < 80 cm < 90 cm < 80 cm
How to Treat
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Lifestyle modificationLifestyle modification
TARGET <140/90 mm Hg (<130/80 mm Hg in diabetes or CKD)
Beta blocker*
Beta blocker*
Long-acting CCB
Long-acting CCBARBARBACE-IACE-IThiazide
diureticThiazide diuretic
CONSIDER:• Non-adherence• Secondary HTN• Interfering drugs or lifestyle• White coat effect
CONSIDER:• Non-adherence• Secondary HTN• Interfering drugs or lifestyle• White coat effect
Dual combinationDual combination
Triple or quadruple therapy
Triple or quadruple therapy
Initial therapyInitial therapy
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
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
*Not indicated as first-line therapy > 60 years.
Special Cases/Drug Classes
•ARV Drug Interactions: http://www.hivclinic.ca/main/drugs_interact.html
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Indication Target BP Recommended Drugs*
Post MI < 140/90 mm HgBeta-blocker + ACE-I or ARB
CKD < 130/80 mm Hg ACE-I or ARB
Diabetes with nephropathy < 130/80 mm Hg ACE-I or ARB
Diabetes without nephropathy
< 130/80 mm HgACE-I, ARB, or thiazide diuretic or DHP-CCB
Stroke/TIA < 140/90 mm Hg ACE-I/diuretic combination
Follow-up of Hypertension
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Symptoms, severe hypertension, intolerance to anti-hypertensive treatment
or target organ damage
Symptoms, severe hypertension, intolerance to anti-hypertensive treatment
or target organ damage
Treatment: pharmacological or non-pharmacological
Treatment: pharmacological or non-pharmacological
Diagnosis of hypertensionDiagnosis of hypertension
Are BP readings below target during 2 consecutive visits?Are BP readings below target during 2 consecutive visits?
Follow-up at 3-6 month intervals
Follow-up at 3-6 month intervals
More frequent
visits
More frequent
visits
Visit every 1-2 months
Visit every 1-2 months
NoYes
Yes No
Useful Links and Resources
CHEP Hypertension Recommendations 2009www.hypertension.ca/chep/recommendations-2009
Patient Guides for Home BP Monitoring and Dietwww.hypertension.qc.ca (french)
http://hypertension.ca/chep/educational-resources/public-information/ (english)
Toronto General Hospital HIV Clinic – Drug Interaction Tableswww.hivclinic.ca/main/drugs_interact.html (look up individual cardiac medications in PI and NNRTI tables)
Management of Kidney Disease
Management of Kidney Disease
HIV and the Kidney
• The renal tubules have clearly been demonstrated to be a reservoir for HIV infection
• Active viral replication in renal tubular cells can result in high-grade proteinuria with rapid decline in renal function
– Pathological diagnosis: HIV-associated nephropathy (HIVAN)
– HIVAN seen almost exclusively in individuals of African descent who are not actively treated with ARVs
Wyatt CM, Klotman PE. Clin J Am Soc Nephrol 2007;2:S20-24.
National Kidney Foundation. Am J Kidney Dis 2002;39(2 Suppl 1):S1-266.
Classification of CKD
*Modification of Diet in Renal Disease (formula) is recommended for staging of CKD; GFR: glomerular filtration rate
Stage Description GFR *(mL/min/1.73m2)
IAbnormal ultrasound OR hematuria OR proteinuria
> 90
II mild ↓ GFR 60 - 89
III moderate ↓ GFR 30 - 59
IV severe ↓ GFR 15 - 29
V End-stage renal disease < 15
Proteinuria
Low CD4 #
EstablishedCVD
Family hxof CVD
Hypertension
Dyslipidemia
Smoking
Diabetes
African-American descent
Family hx of kidneydisease
Older age
Recreational drug use
Use of nephrotoxicmedications
HBV/HCV co-infection
Orange = non-modifiableBlue = modifiable
Risk Factors For CKD in
HIV
Medications and Renal Disease
Guo X, Nzerue C. Cleve Clin J Med 2002;69:289-312.
TMP/SMX: trimethoprim and sulfamethoxazole
Prerenal Tubular InjuryAllergic
Interstitial Nephritis
Thrombotic Microangiopathy
Obstructive
• ACE-I• Amphotericin• NSAIDS• Cyclosporine• Diuretics• Interferon
• Cidofovir• Adefovir• Tenofovir• Didanosine• Lamivudine• Stavudine• Aminoglycosides• Amphotericin• Cocaine• Foscarnet• Pentamidine
• Abacavir• Indinavir• Ritonavir• Acyclovir• Cephalosporins• Penicillins• Ciprofloxacin• TMP/SMX• Rifampin
• Indinavir• Cocaine• Cyclosporine• Valacyclovir
• Indinavir• Atazanavir• Acyclovir• Foscarnet• Sulfadiazine• Sulfonamides
CKD in HIV: 10-Step Approach
1. Confirm finding with repeat testing2. Estimate renal function in terms of GFR
• MDRD formula recommended for CKD staging
3. Determine rate of change of renal function4. Quantify the degree of proteinuria
• Normal: < 150 mg/day of proteinuria; < 30 mg/day albuminuria
5. Assess for the presence of hematuria6. Identify potential nephrotoxins
• NSAIDS, IV contrast dye, aminoglycosides, high-dose acyclovir, amphotericin B, cidofovir (and caution with adefovir)
7. Rule out ECF volume depletion or urinary obstruction8. Identify risk factors for CKD
• Diabetes mellitus, hypertension, smoking history, dyslipidemia, family history of CVD, established CVD, low CD4 count
9. Renally dose ALL medications• Cockcroft-Gault formula recommended for drug dosing
10.Consider a nephrology referral
Initial Work-up for CKD in HIV
*with repeat testingCr: creatinine; Ca: calcium; Mg: magnesium; CBC: complete blood count; eGFR: estimated glomerular filtration rate;
CrCl: creatinine clearance
Initial workup When to refer
Serum
• Cr, electrolytes, Ca, Mg, phosphate, albumin
• CBC, liver enzymes and liver function tests
• Hepatitis B & C serologies
• Screen for diabetes mellitus, lipid profile
• Acute renal failure
• Rapidly declining renal function
• eGFR < 30 mL/min
Urine
• Spot urine albumin:creatinine ratio
AND/OR
• 24-hr collection for CrCl and proteinuria
• Persistent proteinuria
• Albumin:Cr ratio > 60*
• Protein:Cr ratio > 90*
Imaging
• Renal ultrasound • Urological assessment if evidence of obstruction
Management of CKD
Control Risk Factors for CKD • Hypertension: target BP < 130/80 mm Hg; consider ACE-I or ARB as initial choice• Diabetes: target HbA1C < 7%• Dyslipidemia: treat stage 1-3 CKD according to general population guidelines; treat stage 4 CKD to LDL-C < 2.0 mmol/L• Established CVD: antiplatelet therapy, statins, ACE-I or ARBs
Control Risk Factors for CKD • Hypertension: target BP < 130/80 mm Hg; consider ACE-I or ARB as initial choice• Diabetes: target HbA1C < 7%• Dyslipidemia: treat stage 1-3 CKD according to general population guidelines; treat stage 4 CKD to LDL-C < 2.0 mmol/L• Established CVD: antiplatelet therapy, statins, ACE-I or ARBs
Delay Progression of CKD• Treat underlying risk factor/disease• Avoid nephrotoxins (especially NSAIDS)• Treat proteinuria
- ACE-1 or ARB; titrate as toletated by BP and serum potassium- Dietary counselling on potassium restriction and/or diuretics to control serum potassium
• Target BP < 130/80 mm Hg
Delay Progression of CKD• Treat underlying risk factor/disease• Avoid nephrotoxins (especially NSAIDS)• Treat proteinuria
- ACE-1 or ARB; titrate as toletated by BP and serum potassium- Dietary counselling on potassium restriction and/or diuretics to control serum potassium
• Target BP < 130/80 mm Hg
Reduce CVD RiskReduce CVD Risk
Treat Metabolic Complications of CKD• Anemia• Disorders of the bone mineral metabolism
Treat Metabolic Complications of CKD• Anemia• Disorders of the bone mineral metabolism
• Potassium• Acidosis
Summary
• Risk factors for CKD and CVD are similar
• Management of patients with CKD involves:– Controlling risk factors: diabetes, hypertension
– Delaying progression
– Reducing CVD risk
– Avoiding nephrotoxins (consider OTC use of NSAIDS)
– Renally dosing all medications
• Specialist/nephrologist opinion should be considered for patients with rapidly falling GFR, GFR < 30 mL/min, and persistent proteinuria despite conservative therapy
Useful Links and Resources
eGFR calculator, nutritional guide, patient & health practitioner information on CKD www.ukidney.com
Canadian Guidelines for CKDwww.cmaj.ca/cgi/content/full/179/11/1154
IDSA Guidelines for CKD in HIVwww.journals.uchicago.edu/doi/pdf/10.1086/430257
ARV Dosing Adjustments for Impaired Renal Functionwww.aidsetc.org/aidsetc?page=et-03-00-02
Management of Lipids
Management of Diabetes
Smoking Cessation Counselling
CVD Risk and Assessment
Management of Kidney Disease
Management of Hypertension
Overview