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 Kidney
Disease
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
and Assessment
CVD Risk Factors in the
HIV Population
hsCRP?
Lipids*
Inactivity,
Diet
Gender
Abdominal
Obesity*
Age
CVD
Risk
Family
History
HIV
Infection
Orange = Modifiable
Green = Non-modifiable
Purple = HIV-associated
*Metabolic syndrome
Cigarette
Smoking
ARV
Hypertension*
Hyperglycemia*
Insulin
Resistanc
e
Diabetes
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-Based
Guidelines 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…
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-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
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
Adapted from Smieja M, et al. Canadian Evidence-Based Guidelines on Cardiovascular Risk in HIV [in development].
Screening for all patients:
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
• Baseline, before ART, 3-6 months after
starting ART, then annually*
• Consider hs-CRP
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
ART: antiretroviral therapy; EtOH: ethyl alcohol; BMI: body mass index; BP: blood pressure; TC: total cholesterol; HDL-C: high-density lipoprotein
cholesterol; 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 HIVspecific 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
Smoking Cessation
Counselling
Tobacco Dependence is a
Medical Condition
What are the effects
of nicotine?
PHYSICAL
DEPENDENCE
Why do people continue
to smoke?
Drop in nicotine levels
leads to craving and
withdrawal
Smoking prevalence: General population:
20%
HIV population:
40-70%
Heishman SJ. Nicotine Tob Res 1999;1(Suppl 2):S143-7.
The 5A’s Model
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
Further information on this model available at: http://ctica.org
ASK…(at every visit)
Is he/she
currently Yes
smoking?
No
Make note in
file and
address
at future
appointments
Has he/she
Would he/she
considered Yes like your
quitting?
help to quit?
No
Make note in
file and offer
assistance
when patient is
ready
Yes
No
Make note in
file and
address
at future
appointments
Discuss
smoking
cessation or
arrange an
appointment
to address
next steps
in strategy1
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
The healthcare provider focuses their efforts
and education to best motivate the patient to
move across this continuum
to the right
Knowledge
Skills
Changes in Attitude
Enablers
Reward System
Reinforcements
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:
1.
2.
3.
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
Medication
Nicotine gum
Nicotine
patch
Nicotine
inhaler
Bupropion*
Varenicline
Treatment
length
1-3 months
8-12 weeks
12-24 weeks
7-12 weeks
12 weeks
Main side
effects
Dosage
• Upset
stomach
• Hiccups
2 mg, 4 mg
• Headache
• Disturbed
sleep
• Site rash
7 mg,
14 mg,
21 mg
• Irritation of
throat and
nasal
passages
• Sneezing
• Coughing
6-12
cartridges per
day
• Insomnia
150 to
300 mg/day
• Nausea
• Depression
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.





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: 1-877-513-5333
www.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 Canada
www.smoke-free.ca
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:
Genest J. et al. Can J. Cardiol 2009;25:567-79.
estimated glomerular filtration rate; HAART: highly-active
antiretroviral therapy
First Steps to Managing
Lipids
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
Assess Co-morbidities*
Determine Lipid Targets
• Calculate using Framingham
<10% = LOW RISK
10%- 19% = MODERATE RISK
>20% = HIGH RISK
• Consider calculating Reynolds Risk
Score (if hs-CRP assessed)
•
•
•
•
•
• LOW RISK: ≥ 50% ↓ LDL-C
Diabetes mellitus
Coronary heart disease
Previous CV event
Atherosclerosis
Aneurysm
*ANY = HIGH RISK
** 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.
Adapted from Genest J, et al. Can J Cardiol 2009;25:567-79.
• 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
TREAT TO TARGET
TREAT TO TARGET
Low-to-Moderate Risk
High-risk
Start with…
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
If lipid targets are not met with
3- to 6-month trial…
Pharmaceutical Management
Lipid-Lowering Therapy
Altering ARV 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
• 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
When to Treat
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%
Low
• Framingham: < 10%
•
•
•
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)
•
LDL-C ≥ 5.0 mmol/L
**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
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
*Secondary (optional targets) once LDL-C at goal:
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.
—
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
Lipid-Lowering Agents and
PIs: Drug Interactions
Fenofibrate
Fluvastatin
Ezetimibe
Fish oil
Statin + fibrate
Atorvastatin
Rosuvastatin
Pravastatin*
Niacin
Gemfibrozil
Lovastatin
Simvastatin
Low interaction
potential
Use cautiously:
“START LOW-GO SLOW “
http://www.hivclinic.ca/main/drugs_interact_files/LIPID-drugs.pdf
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)
Management
of Diabetes
Diabetes Risk Factors
HIV-associated DM
Risk Factors
Classical DM
Risk Factors
• Abdominal
obesity
• Physical inactivity
• Genetic
Insulin
Resistance
• Family history
• Race/ethnicity
• Older age
• Dyslipidemia
•
•
•
•
•
•
•
Peripheral lipoatrophy
Reduced adiponectin
Increased liver/muscle fat
Inflammatory cytokines
Low testosterone
HCV co-infection
Protease inhibitors, d4T
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
OR
AND/OR
Casual PG > 11.1 mmol/L
with symptoms of polydipsia or polyuria
or unexplained weight loss
OR
7.8-11.1
mmol/L
IFG
and/or
IGT
Confirmed
by any of
these 3
laboratory
tests on
another day
2h PG in a 75-g OGTT > 11.1 mmol/L
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.
Management of Diabetes
DIABETES
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
Alphaglucosidase
inhibitor
Incretin
DDP-4
inhibitor
i.e., acarbose
i.e. sitagliptin
Secretagogue
TZD
i.e., glicazide,
glyburide
i.e., pioglitazone
**AVOID
in CHF
Adapted from Canadian Diabetes Association. Can J Diabetes 2008;32(Suppl 1):S1-S201.
Insulin:
sooner for
A1C > 9.0%
or metabolic
syndrome
Targets For Treatment
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
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)
Management
of Hypertension
Diagnosis of Hypertension
Elevated Out of
the Office BP
Measurement
Elevated Random
Office BP
Measurement
Hypertension Visit 1
Hypertensive
Urgency/
Emergency
BP Measurement,
History and
Physical Examination
Diagnostic tests
ordering at visit 1 or 2
Hypertension Visit 2
within 1 month
BP >140/90 mmHg and Target
Organ Damage or Diabetes
or Chronic Kidney Disease
or BP >180/110?
Yes
Diagnosis
of HTN
No
BP: 140-179 /90-109 mm Hg
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Diagnosis of Hypertension
(cont’d)
BP: 140-179 / 90-109 mm Hg
Clinic BP
ABPM (if available)
Hypertension Visit 3
≥160 SBP or
Diagnosis
of HTN
≥100 DBP
<160 / 100
or
ABPM or
HBPM
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
Continue to
follow-up
Diagnosis
of HTN
Continue to
follow-up
Hypertension Visits 4-5
≥140 SBP or
Diagnosis
of HTN
≥90 DBP
<140 / 90
Continue to
follow-up
Home BPM
≥135/85
or
Diagnosis
of HTN
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
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
≥ 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
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
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
Initial therapy
Thiazide
diuretic
CONSIDER:
• Non-adherence
• Secondary HTN
• Interfering drugs
or lifestyle
• White coat effect
ACE-I
ARB
Dual combination
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
Longacting CCB
Beta
blocker*
*Not indicated as first-line
therapy > 60 years.
Triple or quadruple
therapy
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
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
< 94 cm
< 90 cm
Women
< 80 cm
< 80 cm
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
How to Treat
TARGET <140/90 mm Hg (<130/80 mm Hg in diabetes or CKD)
Lifestyle modification
Initial therapy
Thiazide
diuretic
CONSIDER:
• Non-adherence
• Secondary HTN
• Interfering drugs
or lifestyle
• White coat effect
ACE-I
ARB
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
Longacting CCB
Beta
blocker*
Dual combination
*Not indicated as first-line
therapy > 60 years.
Triple or quadruple
therapy
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Special Cases/Drug Classes
Indication
Target BP
Recommended Drugs*
Post MI
< 140/90 mm Hg
Beta-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 Hg
ACE-I, ARB, or thiazide
diuretic or DHP-CCB
Stroke/TIA
< 140/90 mm Hg
ACE-I/diuretic
combination
•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
Follow-up of Hypertension
Diagnosis of hypertension
Treatment: pharmacological or nonpharmacological
Are BP readings below target during 2 consecutive visits?
Yes
Follow-up at 3-6 month
intervals
No
Symptoms, severe
hypertension, intolerance to
anti-hypertensive treatment
or target organ damage
Yes
More
frequent
visits
No
Visit every 12 months
Adapted from the 2009 CHEP Recommendations. Available at: www.hypertension.ca/chep/recommendations-2009
Useful Links and Resources
CHEP Hypertension Recommendations 2009
www.hypertension.ca/chep/recommendations-2009
Patient Guides for Home BP Monitoring and Diet
www.hypertension.qc.ca (french)
http://hypertension.ca/chep/educational-resources/publicinformation/ (english)
Toronto General Hospital HIV Clinic – Drug Interaction
Tables
www.hivclinic.ca/main/drugs_interact.html
(look up individual cardiac medications in PI and NNRTI tables)
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.
Classification of CKD
Stage
Description
GFR *(mL/min/1.73m2)
I
Abnormal 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
*Modification of Diet in Renal Disease (formula) is recommended for staging of CKD; GFR: glomerular filtration rate
National Kidney Foundation. Am J Kidney Dis 2002;39(2 Suppl 1):S1-266.
Recreational
drug use
Diabetes
Family hx
of kidney
disease
Proteinuria
Low CD4 #
HBV/HCV
co-infection
Orange = non-modifiable
Blue = modifiable
Established
CVD
Smoking
Risk Factors
For CKD in
HIV
AfricanAmerican
descent
Dyslipidemia
Hypertension
Family hx
of CVD
Older age
Use of
nephrotoxic
medications
Medications and
Renal Disease
Prerenal
•
•
•
•
•
•
ACE-I
Amphotericin
NSAIDS
Cyclosporine
Diuretics
Interferon
Allergic
Interstitial
Nephritis
Tubular Injury
•
•
•
•
•
•
•
•
•
•
•
Cidofovir
Adefovir
Tenofovir
Didanosine
Lamivudine
Stavudine
Aminoglycosides
Amphotericin
Cocaine
Foscarnet
Pentamidine
•
•
•
•
•
•
•
•
•
Abacavir
Indinavir
Ritonavir
Acyclovir
Cephalosporins
Penicillins
Ciprofloxacin
TMP/SMX
Rifampin
TMP/SMX: trimethoprim and sulfamethoxazole
Guo X, Nzerue C. Cleve Clin J Med 2002;69:289-312.
Thrombotic
Microangiopathy
•
•
•
•
Indinavir
Cocaine
Cyclosporine
Valacyclovir
Obstructive
•
•
•
•
•
•
Indinavir
Atazanavir
Acyclovir
Foscarnet
Sulfadiazine
Sulfonamides
CKD in HIV:
10-Step Approach
1. Confirm finding with repeat testing
2. Estimate renal function in terms of GFR
• MDRD formula recommended for CKD staging
3. Determine rate of change of renal function
4. Quantify the degree of proteinuria
• Normal: < 150 mg/day of proteinuria; < 30 mg/day albuminuria
5. Assess for the presence of hematuria
6. 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 obstruction
8. 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
Initial workup
When to refer
Serum
• Cr, electrolytes, Ca, Mg, phosphate, albumin • Acute renal failure
• CBC, liver enzymes and liver function tests
• Rapidly declining renal function
• Hepatitis B & C serologies
• eGFR < 30 mL/min
• Screen for diabetes mellitus, lipid profile
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
*with repeat testing
Cr: creatinine; Ca: calcium; Mg: magnesium; CBC: complete blood count; eGFR: estimated glomerular filtration rate;
CrCl: creatinine clearance
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
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
Treat Metabolic Complications of CKD
• Anemia
• Disorders of the bone mineral metabolism
• Potassium
• Acidosis
Reduce CVD Risk
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 CKD
www.cmaj.ca/cgi/content/full/179/11/1154
IDSA Guidelines for CKD in HIV
www.journals.uchicago.edu/doi/pdf/10.1086/430257
ARV Dosing Adjustments for Impaired Renal Function
www.aidsetc.org/aidsetc?page=et-03-00-02
Overview
CVD Risk and Assessment
Smoking Cessation Counselling
Management of Lipids
Management of Diabetes
Management of Hypertension
Management of Kidney Disease