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Toronto Notes 2019
Dyslipidemias
Endocrinology E5
SECONDARY CAUSES
Etiology
• endocrine:obesity/metabolicsyndrome,DM
• drugs:β-blockers,anabolicsteroids
• other:acuteinfections,inflammatoryconditions
Dyslipidemia and the Risk for Coronary Artery Disease
• increasedLDLisamajorriskfactorforatherosclerosisandCADasLDListhemajoratherogeniclipid particle
• increasedHDLisassociatedwithdecreasedcardiovasculardiseaseandmortality
• moderatehypertriglyceridemia(triglyceridelevel2.3-9mmol/L)isanindependentriskfactorforCAD,
especially in people with DM and in post-menopausal women
• treatmentofhypertriglyceridemiahasnotbeenshowntoreduceCADrisk
Screening
• screenmen>40yr,women>50yrorpost-menopausal • iffollowingriskfactorspresent,screenatanyage:
■ DM
■ current cigarette smoking or COPD
■ HTN (sBP >140, dBP >90), hypertensive diseases of pregnancy
■ obesity (BMI 30 kg/m2)
■ family history of premature CVD
■ clinical signs of hyperlipidemia (xanthelasma, xanthoma, arcus cornealis)
■ clinical evidence of abdominal aneurysm
■ clinical evidence of atherosclerosis
■ inflammatory disease (rheumatoid arthritis, SLE, psoriatic arthritis, ankylosing spondylitis,
inflammatory bowel disease)
■ HIV infection on highly active anti-retroviral therapy (HAART) ■ chronic kidney disease (estimated GFR <60 mL/min/1.73 m2)
■ erectile dysfunction
■ high risk ethnicity: south Asian, First Nations
• screenchildrenwithafamilyhistoryofhypercholesterolemiaorchylomicronemia
Factors Affecting Risk Assessment
• metabolicsyndrome
• apolipoproteinB(apoB)
■ each atherogenic particle (VLDL, IDL, LDL, and lipoprotein A) contains one molecule of apo B
■ serum [apo B] reflects the total number of particles and may be useful in assessing cardiovascular
risk and adequacy of treatment in high risk patients and those with metabolic syndrome • Lp(a)levelsmayhelpstratifyingthoseatintermediaterisk
• coronaryarterycalcium(CAC)mayhelpstratifyingthoseatintermediaterisk
• C-reactiveprotein(hs-CRP)levels
■ highly sensitive acute phase reactant
■ may be clinically useful in identifying those at a higher risk of cardiovascular disease than predicted
by the global risk assessment
Treatment of Dyslipidemias
Treatment Effect
Each 1.0 mmol/L decrease in LDL corresponds to 20-25% relative risk reduction in cardiovascular disease
6% Rule
If the dose of a statin is doubled, there is approximately a 6% increase in the LDL lowering efficacy
For Statin Follow-Up
• Liver enzymes and lipid profile: liver enzymes measured at the beginning of treatment then once after therapy initiated. Lipids (once stabilized) measured annually. Order both if patient complains of jaundice, RUQ pain, dark urine
• CK at baseline and if patient complains of myalgia
• D/C statin if CK >10x upper limit of normal or patient has persistent myalgia
The American Approach to LDL Lowering
A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines
Circulation 2013;00:000-000
Purpose: To examine the evidence supporting specific end-point LDL targets in statin therapy. Study: Systematic review, searching 1995-2009 inclusive identified 19 RCTs.
Results: None of the trials examined demonstrated better cardiovascular outcomes for a particular target LDL. Moreover, many trials showed best outcomes from maximum tolerated dose of statin, irrespective of the treated LDL level.
Conclusion: Based on systematic review, the ACC/ AHA is no longer recommending a “Treat to Target” approach for statin therapy. Primary prevention in patients with increased risk should be treated with moderate to high intensity statin therapy without tracking LDL targets. Similarly, patients needing secondary prevention should receive high intensity statin therapy without attention to LDL targets.
Risk Assessment and Treatment Consideration
Low Risk
FRS<10%
Assess risk using the Framingham Risk Score (FRS) unless a statin-indicated condition Repeat screening every year for FRS 5% and every 5 years for FRS<5%
Intermediate Risk
FRS 10-19%
and LDC-C 3.5mmol/L
or Non-HDL-C 4.3mmol/L or ApoB 1.2g/L
High Risk
FRS 20%
Statin-Indicated Conditions
LD-C 5mmol/L
aka genetic dyslipedemia
LDL-C>50% reduction
If target is NOT achieved with maximally tolerated dose, discuss add-on therapy with patient
Abdominal aortic aneurysm Clinical atherosclerosis Chronic kidney disease Most diabetes
Discuss key health behavioural modifications with patient (smoking cessation, diet, exercise) Initiate Statin Treatment
©Kim Nipp 2019
LDL-C<2.0mmol/L or >50% reduction or apoB<0.8g/L or non-HDL-C<2.6mmol/L
Ezetimibe or BAS as 1st line
Ezetimibe or BAS or PCSK9 inhibitors
Figure 3. Dyslipidemia management for the prevention of cardiovascular disease in the adult
Adapted fromL 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Canadian Cardiovascular Society.
Ezetimibe or BAS as 1st line PCSK9 inhibitor as 2nd line
Always monitor
response to statin Rx and health behaviour whether target is achieved or not achieved