Managing Cardiovascular Risk in HIV A Toolkit for HIV Clinicians Management of Lipids Management of Diabetes Smoking Cessation Counselling CVD Risk and

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


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



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?

http://www.clinicaloptions.com/hiv

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


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)


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:


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

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


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



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

http://ctica.org/

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 offer assistance when patient is ready

Make note in file and offer assistance when patient is ready



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

http://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.

http://www.surgeongeneral.gov/tobacco/default.htm

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


http://www.ctica.org/cessation/cessation.html

http://www.smokershelpline.ca/

http://www.surgeongeneral.gov/tobacco/

http://www.mhp.gov.on.ca/english/health/smoke_free/default.asp

http://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 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.

http://www.hivclinic.ca/main/drugs_interact_files/LIPID-drugs.pdf

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


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)




http://www.hivclinic.ca/main/drugs_interact.html



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

http://www.clinicaloptions.com/HIV/Management%20Series/Insulin%20Resistance/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


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


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)

http://www.sgfp.ca/forms.html

http://www.diabetes.ca/for-professionals/resources/2008-cpg/

http://www.hivclinic.ca/main/drugs_interact.html

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

http://www.hypertension.ca/chep/recommendations-2009

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


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



Diagnosisof HTN

Diagnosisof HTN

Home BPMHome BPM

<135/85<135/85 ≥135/85≥135/85



Diagnosisof HTN

Diagnosisof HTN

or


When to Treat

SBP: systolic blood pressure; DBP: diastolic blood pressure


≥ 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


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


Dual combinationDual combination

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


*Not indicated as first-line therapy > 60 years.


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.

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


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



Dual combinationDual combination



Initial therapyInitial therapy



*Not indicated as first-line therapy > 60 years.

Special Cases/Drug Classes

•ARV Drug Interactions: http://www.hivclinic.ca/main/drugs_interact.html


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


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


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)



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


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







Overview

Documents

Managing Cardiovascular Risk in HIV A Toolkit for HIV Clinicians Management of Lipids Management of Diabetes Smoking Cessation Counselling CVD Risk and