Dyslipidemia07

8/12/2019 Dyslipidemia07

1/45

Dyslipidemia: Managing a KeyCardiovascular Risk Factor

AIMGP Clinic Seminar

Updated by R. CavalcantiSep 2007


2/45

Outline

Current Practice GuidelinesCasesGlobal Risk Assessment

Whom to Screen for Dyslipidemia?Risk Categories & Lipid TargetsFactors Influencing Risk Assessment

Selected StudiesManagementCases Revisited


3/45

Current Practice Guidelines

Canadian Guidelines Recommendations for the management of

dyslipidemia and the prevention of cardiovascular

disease: summary of the 2003 update CMAJ169(9):921-4, 28 Oct 2003

www.cmaj.ca/cgi/content/full/169/9/921/DC1 CCS Position Statement on Dx and Rx

dyslipidemia. Canadian Journal of Cardiology2006;22(11):913-927
http://www.cmaj.ca/cgi/content/full/169/9/921/DC1http://www.cmaj.ca/cgi/content/full/169/9/921/DC1


4/45

Current Practice Guidelines

American Guidelines Implications of Recent Clinical Trials for the National

Cholesterol Education Program Adult Treatment Panel

III Guidelines Circulation 110:227-39, 13 July 2004

Third Report of the National Cholesterol EducationProgram (NCEP) Expert Panel on Detection,

Evaluation, and Treatment of High Blood Cholesterolin Adults (Adult Treatment Panel III) JAMA 285(19):2486-97, 16 May 2001


5/45

Case 1

56 M Acute MI 4 months ago No current cardiovascular symptoms

Tested for DM post-MI Negative Non-smoker, no HTN

Lipids measured while in hospital post-MI:

TC 4.2, LDL 2.5, HDL 1.3, TG normal (TC/HDL 3.2)What is his estimated risk of a cardiovascularevent in the next 10 years?How should you manage his lipids?


6/45


7/45


8/45

Current Challenges inCardiovascular Risk ReductionAging Population >20% Canadians will be >65 years old by 2011 1,900,000 Canadians >80 years old by 2026

Obesity 31% of Canadians are obese Especially if abdominal adiposity, associated with

increased prevalence of metabolic syndrome features(DM, HTN, TGs, HDL, insulin resistance)

Associated with inflammatory markers (CRP, IL -6)

Diabetes 60,000 new cases per year in Canada

3,000,000 Canadians with DM by 2010


9/45

Global Risk Assessment

Hyperlipidemia is an important risk factor,and should be used to assess overall cardio-vascular riskGlobal CV risk should be used to assesstreatment goals and modalitiesCardiac endpoints: non-fatal MI death due to CAD


10/45


Risk assessment model adapted from theFramingham Heart Study

This model only applies in: Patients without diabetes Patients without clinically evident

cardiovascular disease (prior CAD, ischemicstroke, PAD) or CRF


11/45


Which patients are automatically consideredhigh risk (>20% 10-year risk)?

All adult patients with: DM History of CAD Ischemic stroke Peripheral arterial disease CRF ( < 60 ml/min of GFR)


12/45


What are the risk factors in Framinghamrisk calculator?

Age Gender Smoking history Lipid profile (TC, HDL) Systolic BP


13/45

If the calculated10-year risk is:

20% - High Risk

11-19% - ModerateRisk

10% - Low Risk


14/45

Whom to Screen forDyslipidemia?

Influenced by cardiac risk factors:By age alone (Canadian Guidelines): Men over age 40

Women over age 50 (or post-menopausal)Adults at any age if: At least 2 risk factors

DM, HTN, Smoking, Abdominal Obesity

Family history of early cardiovascular disease Physical signs of hyperlipidemia

Xanthomata, xanthelasmas, arcus corneae, etc

Evidence of existing atherosclerosis


15/45

Manifestations of Dyslipidemia

Eruptive xanthomata onthe forearm of a patientwith severe TGs

Xanthelasmasand tendonxanthomata in

patients with

severe LDL(the patient atthe bottom hasheterozygousfamilialhyperchol-esterolemia)


16/45

Diagnosis of AsymptomaticAtherosclerosis

To aid in risk stratificationRecommended: Physical examination

Ankle-Brachial IndexPossibly useful in patients already known to be atmoderate risk: Carotid ultrasonography

EKG Exercise stress testing in men >40 years old with

established cardiovascular risk factors


17/45

Risk Categories & Lipid Targets

More about LDL targets to come later for high-risk patients,these are minimum targets they should be lower if at all

possible


18/45

Lipid Targets: Triglycerides

No discrete triglyceride goal in eachcategory, but the optimal level is TG 10 requires targeted treatment to

prevent pancreatitis independent ofcardiovascular risk diet & lifestyle changes fibrate or niacin, fish oil


19/45

Factors Influencing Risk Assessment

Metabolic SyndromeAbdominal Obesity

Apolipoprotein B (apoB)Lipoprotein(a)Homocysteine

C-Reactive Protein (CRP)Genetic Risk


20/45

Factors Influencing RiskAssessment

Presence of the Metabolic Syndrome: Risk A clustering of cardiovascular risk factors, including

abdominal obesity, insulin resistance, and hypertension,

as well as lipid abnormalities ( TGs and HDL )

Presence of Abdominal Obesity: Risk with waist circumference as a useful estimate


21/45


Apolipoprotein B (apoB) A poB (for the same lipid levels) = smaller,

denser, more atherogenic LDL particles ApoB levels correlate better than LDL

levels to clinical outcomes in statin trials For high risk patients, target apoB


22/45


Homocysteine homocysteine levels predict adverse outcomes

in patients with CAD

Fixed-dose folate & B12 supplementation trialsso far have been negative

No evidence yet to screen for homocysteine


23/45


C-Reactive Protein (CRP)

CRP may add prognostic information to

Framingham CRP associated with abdominal obesity and

the metabolic syndrome May be useful in persons with a calculated 10-

year risk of 11-19% ( moderate risk) More aggressive Rx?


24/45


25/45


Genetic Risk A confirmed, unambiguous family history of early

onset CAD increases the risk for first-degree relatives

(parents, siblings, children) RRI 1.7-2.0

Early onset is defined as


26/45

Selected Major Studies

There are many, many, many trials ofstatinsWe will discuss: MRC/HPS- largest trial of 2a. prevention (+ 1a.

prevention in high risk pt) ASCOT-LLA- largest trial of 1a. Prevention INTERHEART: largest study of risk factors


27/45

Selected Major Trials

MRC/BHF Heart Protection Study: 20,556 men & women aged 40-80 with TC >3.5 All at high risk of CAD

Known CAD/MI/PVD/CVS DM, HTN, or both

RCT: Simvastatin 40mg vs. placebo Decreased death rate by 13% at 5 years

Decreased combined cardiovascular end points by 24% Benefits in all subgroups, including baseline LDL


28/45

Selected Major Trials

Anglo-Scandinavian Cardiac Outcomes Trial 9000 patients aged 40-79 with baseline TC


29/45

Selected Major Studies

The INTERHEART study Potentially modifiable risk factors associated

with MI in 52 countries:

Case Control: 15,152 cases & 14,820 controlsin 52 countries on every inhabited continent

Findings consistent between old/young,male/female, different countries

9 risk factors accounted for >90% of the risk (in men) >94% of the risk (in women)

Lancet 364(9437):4999-5014, 4 Sept 2004


30/45

The INTERHEART studyIncrease risk ApoB/ApoA1 ratio

OR 3.25

Smoking (current vs. never) OR 2.87

Psychosocial factors OR 2.67

DM OR 2.37

History of HTN OR 1.91

Abdominal Obesity OR 1.12 1 st vs. 3 nd tertile

OR 1.62 2nd

vs. 3rd

tertile

Protective: eating fruits &

vegetables daily OR 0.70

3 units/week ofalcohol

OR 0.91

moderate/strenuous

physical activity OR 0.86


31/45

Treatment


32/45

Treatment


33/45

Treatment

In low or moderate risk patients Start with lifestyle, progress to Rx based on targets

In high risk patients:

Start drug treatment immediately (statin), concurrentlywith diet and lifestyle modification Priority is to get LDL


34/45

2004 ATP III Update


35/45

Lower LDL Targets

In high risk patients mounting evidencesupports lower LDL-C targets

Latest CCS guidelines (CJC 2006): High risk patients: LDL-C < 2.0; TC:HDL


36/45

Treatment

If TC/HDL ratio is still high: Lifestyle modification Increasing Statin Dose (with LDL at target) Combination Drug Therapy


37/45


38/45

Treatment

Increasing Statin Dose (with LDL at target): For HDL and/or mild TGs (TGs


39/45

Treatment

Combination Drug Therapy (Limited if any evidence) : Moderate TGs -> add salmon oil (1-3g tid) to statin HDL -> combine statin with niacin. Caution:

1) niacin can cause increased insulin resistance 2) niacin-statin combination increases risk of hepatotoxicity

If intolerant to niacin: consider statin-fibrate combination

(simvastatin or pravastatin with fenofibrate, NOT gemfibrozil) lowest possible doses of each very close follow-up watching for hepatotoxicity and myositis if no CRF


40/45

Treatment

If TGs: Ideal target 6 despite lifestyle changes, need drug treatmenteven if the TC/HDL ratio is acceptable

Treatment is needed to avoid pancreatitis Options:

Fibrate NiacinSalmon oil


41/45

Follow-Up

Which blood work should be orderedin follow-up? How frequently?


42/45

Follow-Up

Lipids: 6 weeks after start / change of dose (levels reach steady

state within 6 weeks of start/change of medication) Long-term follow-up every 6-12 months

AST / ALT (0.5 3% incidence): Get baseline Use with caution if AST/ALT > 3 x normal At 12 weeks after initiation or change in dose (FDA)

CK (< 0.5% incidence): Get baseline Check only if symptomatic with myalgias (ATP III

guideline)


43/45

Case 1 Revisited

56 M Acute MI 4 months ago No current cardiovascular symptoms Tested for DM post-MI

Negative

Non-smoker, no HTN

Lipids measured while in hospital post-MI: TC 4.2, LDL 2.5, HDL 1.3, TG normal (TC/HDL 3.2)

What is his estimated risk of a cardiovascularevent in the next 10 years? Assumed to be 20%

How should you manage his lipids?


44/45

Case 2 Revisited

45 F Healthy, BP 125/80 Non-smoker, 3 units EtOH/week No cardiovascular symptoms

Lipids measured at annual visit: TC 6.5, LDL 4.1, HDL 1.4, TG normal (TC/HDL 4.6)

What is her estimated risk of a cardiovascular

event in the next 10 years? Calculated to be 1%

How should you manage her lipids?


45/45

Case 3 Revisited

55 F DM Type 2 x 10 years (HbA1c 9.7%), HTN post menopausal, BMI 33 Non-smoker, 4 units EtOH/day No cardiovascular symptoms

Lipids measured at annual visit: TC 5.9, HDL 0.78, TG 9.8 (TC/HDL 7.6)

What is her estimated risk of a cardiovascularevent in the next 10 years? Assumed to be 20%

How should you manage her lipids?

Dyslipidemia07

Documents