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Internal MedicineCardiologyAbnormal Lipids

Abnormal Lipids (Dyslipidemia)

Introduction

Dyslipidemia is a major modifiable risk factor for cardiovascular disease (CVD), which remains a leading cause of death in Canada. For MCCQE1 preparation, understanding lipid management is critical not only for the Cardiology section but also for General Practice and Preventative Medicine.

As a future Canadian physician, you must demonstrate the CanMEDS Health Advocate role by effectively screening, diagnosing, and managing lipid abnormalities to prevent myocardial infarctions, strokes, and peripheral arterial disease.

MCCQE1 Objective Highlight

The MCCQE1 expects candidates to distinguish between primary and secondary dyslipidemia, apply Canadian risk stratification tools (Framingham), and implement evidence-based management strategies based on the Canadian Cardiovascular Society (CCS) guidelines.

Epidemiology and Classification

In Canada, approximately 45% of adults aged 18 to 79 have dyslipidemia. It is often asymptomatic until a cardiovascular event occurs.

Classification of Dyslipidemia

Dyslipidemia can be classified based on the lipid profile (hypercholesterolemia, hypertriglyceridemia, or mixed) or by etiology (primary vs. secondary).

Primary dyslipidemias are genetic disorders leading to abnormal lipid metabolism.

  • Familial Hypercholesterolemia (FH):
    • Heterozygous: Common (1 in 250 Canadians). LDL-C usually < 5.0 mmol/L. Premature CVD.
    • Homozygous: Rare. LDL-C > 13.0 mmol/L. CVD in childhood.
    • Physical signs: Tendon xanthomas (Achilles), xanthelasma, corneal arcus (before age 45).
  • Familial Combined Hyperlipidemia: Elevated LDL and Triglycerides (TG).
  • Familial Hypertriglyceridemia: Isolated high TG.

Screening and Diagnosis

Who to Screen? (CCS Guidelines)

According to the 2021 Canadian Cardiovascular Society (CCS) Guidelines, screening with a lipid profile (TC, LDL-C, HDL-C, non-HDL-C, TG) is recommended for:

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Standard Screening Criteria:

  • Men ≥\ge 40 years of age
  • Women ≥\ge 40 years of age (or post-menopausal)

Screen at ANY age if the following risk factors are present:

  • Clinical evidence of atherosclerosis (CAD, PAD, CVD).
  • Abdominal aortic aneurysm (AAA).
  • Diabetes Mellitus.
  • Arterial hypertension.
  • Current cigarette smoking.
  • Stigmata of dyslipidemia (arcus cornealis, xanthelasma, xanthoma).
  • Family history of premature CVD (Men < 55, Women < 65 in 1st-degree relative).
  • Chronic Kidney Disease (eGFR < 60 mL/min/1.73 m2^2).
  • Obesity (BMI > 30 kg/m2^2).
  • Inflammatory diseases (SLE, RA, Psoriasis).
  • HIV infection on HAART.
  • Erectile dysfunction.

The Lipid Profile

In Canada, patients do not generally require fasting for lipid screening unless triglycerides are > 4.5 mmol/L.

  • LDL-C (Low-Density Lipoprotein Cholesterol): Primary target for therapy.
  • Non-HDL-C: (Total Cholesterol - HDL). A better marker than LDL if TG are elevated.
  • ApoB: Optional but highly specific; indicates total number of atherogenic particles.

Cardiovascular Risk Assessment

In primary prevention, the decision to treat is based on the estimated 10-year risk of a cardiovascular event. Canada primarily uses the Framingham Risk Score (FRS) modified for the Canadian population.

Calculating Risk (FRS)

The FRS considers:

  1. Age
  2. Sex
  3. Smoking status
  4. Total Cholesterol
  5. HDL Cholesterol
  6. Systolic Blood Pressure
  7. Treatment for Hypertension (Yes/No)
  8. Diabetes (Yes/No)

Risk Categories and LDL Targets

Risk Category10-Year FRS Risk %Treatment IndicationPrimary Target (LDL-C)
High Risk≥ 20% (or FRS 10-19% with LDL > 3.5)Initiate Statin< 2.0 mmol/L (or ≥ 50% decrease)
Intermediate Risk10% – 19%Discuss Statin if LDL ≥ 3.5 or ApoB ≥ 1.2< 2.0 mmol/L (or ≥ 50% decrease)
Low Risk< 10%Lifestyle modification≥ 50% decrease (if treated)
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Statin-Indicated Conditions (High Risk regardless of FRS): Patients with these conditions automatically require statin therapy:

  1. Clinical Atherosclerosis (MI, Angina, Stroke, TIA, PAD).
  2. Abdominal Aortic Aneurysm.
  3. Most Diabetes Mellitus:
    • Age ≥ 40 years, OR
    • Age ≥ 30 years with duration > 15 years, OR
    • Microvascular complications.
  4. Chronic Kidney Disease: Age > 50 with eGFR < 60 or albuminuria.
  5. LDL-C ≥ 5.0 mmol/L (Suspected Familial Hypercholesterolemia).

Management

Management follows a stepwise approach focusing on lifestyle first (unless high risk) followed by pharmacotherapy.

Step 1: Health Behaviour Interventions

All patients should be counseled on lifestyle modifications:

  • Diet: Mediterranean diet or DASH diet. Reduce saturated fats and trans fats. Increase fiber, fruits, vegetables, and omega-3 fatty acids.
  • Exercise: 150 minutes of moderate-to-vigorous aerobic activity per week (accumulated in bouts of 10 mins or more).
  • Smoking Cessation: Crucial for risk reduction.
  • Alcohol: Moderate intake.
  • Weight Management: Target BMI 18.5–24.9 kg/m2^2 and waist circumference < 102 cm (men) / < 88 cm (women).

Step 2: HMG-CoA Reductase Inhibitors (Statins)

Statins are the first-line pharmacotherapy. They inhibit cholesterol synthesis and upregulate LDL receptors.

  • High Intensity: Atorvastatin (40-80 mg), Rosuvastatin (20-40 mg).
  • Moderate Intensity: Atorvastatin (10-20 mg), Rosuvastatin (5-10 mg), Simvastatin (20-40 mg).
  • Adverse Effects: Myalgia (common), Myopathy (rare), Rhabdomyolysis (very rare), slight increase in HbA1c, transient LFT elevation.

Step 3: Adjuvant Therapy

If targets are not met with maximally tolerated statin therapy:

  1. Ezetimibe: Inhibits intestinal cholesterol absorption. Added to statin.
  2. PCSK9 Inhibitors (Evolocumab, Alirocumab): Monoclonal antibodies (injectable) that dramatically lower LDL. Used for FH or very high-risk secondary prevention not at target.
  3. Icosapent Ethyl: Pure EPA (omega-3). Indicated for patients with established CVD, on statins, with elevated TG (1.5–5.6 mmol/L).

Step 4: Managing Hypertriglyceridemia

  • Primary intervention: Diet (reduce simple sugars/alcohol), weight loss, glycemic control.
  • If TG > 10.0 mmol/L (risk of pancreatitis): Fibrates (e.g., Fenofibrate) are first line to prevent pancreatitis.
  • Note: Do not combine Gemfibrozil with Statins (high risk of rhabdomyolysis). Fenofibrate is safer with statins.

Canadian Guidelines (CCS 2021 Update)

The Canadian Cardiovascular Society (CCS) guidelines are the gold standard for the MCCQE1.

  1. Lower Targets: For patients with established CVD (Secondary Prevention), the LDL-C target is < 1.8 mmol/L.
  2. Non-Fasting: Non-fasting lipid testing is acceptable for most patients.
  3. Lp(a): Consider measuring Lipoprotein(a) once in a lifetime for risk stratification, especially in those with premature CVD or strong family history.
  4. CAC Score: Coronary Artery Calcium scoring can be considered for “Intermediate Risk” patients to help decide on statin initiation.

Key Points to Remember for MCCQE1

  • Secondary Causes: Always check TSH (hypothyroidism) and HbA1c (diabetes) before diagnosing primary dyslipidemia or starting lifelong meds.
  • Rhabdomyolysis: If a patient on a statin presents with muscle pain and dark urine, order CK and Creatinine immediately. Stop the statin.
  • Teratogenicity: Statins are contraindicated in pregnancy (Category X). Stop statins 3 months before attempting conception.
  • Liver Enzymes: Baseline ALT is required. Routine monitoring is not required unless symptoms suggest hepatotoxicity.
  • Elderly: In primary prevention for those > 75 years, the benefit of statins is less clear; engage in shared decision-making.

Mnemonic: Secondary Causes of Hyperlipidemia

“4 D’s”

  • Diet (Saturated fat, Alcohol)
  • Drugs (Thiazides, Steroids, Retinoids, Antipsychotics)
  • Disorders of metabolism (Hypothyroidism, Nephrotic syndrome)
  • Diseases (Diabetes, Renal failure, Liver disease)

Sample Question

Clinical Scenario

A 52-year-old man presents to your family practice clinic for a periodic health assessment. He has no specific complaints. His past medical history is significant for hypertension, for which he takes perindopril. He has smoked 1 pack of cigarettes daily for 30 years. He does not have diabetes.

Physical Examination:

BP: 148/92 mmHg


BMI: 29 kg/m2


Heart and Lungs: Unremarkable.


No xanthomas or xanthelasmas observed.

Laboratory Results:

Total Cholesterol: 6.2 mmol/L


HDL Cholesterol: 0.9 mmol/L


LDL Cholesterol: 4.1 mmol/L


Triglycerides: 2.1 mmol/L


Glucose (fasting): 5.4 mmol/L


Creatinine: 88 µmol/L

Based on the Canadian Cardiovascular Society guidelines, which one of the following is the most appropriate initial management step?

  • A. Reassure the patient and repeat lipid profile in 1 year
  • B. Initiate lifestyle modifications alone and reassess in 6 months
  • C. Initiate Rosuvastatin 20 mg daily immediately
  • D. Order a Coronary Artery Calcium (CAC) score to determine risk
  • E. Initiate Fenofibrate 145 mg daily

Explanation

The correct answer is:

  • C. Initiate Rosuvastatin 20 mg daily immediately

Detailed Analysis:

  1. Risk Calculation: This patient requires a cardiovascular risk assessment using the Framingham Risk Score (FRS).
    • Factors: Male, 52 years old, Smoker, Treated Hypertension (BP 148/92), Low HDL (0.9), High Total Cholesterol (6.2).
    • Calculation: While you don’t need to calculate the exact percentage mentally, the combination of age, male sex, smoking, HTN, and dyslipidemia places him firmly in the High Risk category (FRS ≥\ge 20%).
  2. CCS Guidelines: For patients at High Risk (FRS ≥\ge 20%), the recommendation is to initiate statin therapy immediately alongside health behaviour interventions. Lifestyle modification alone (Option B) is insufficient for high-risk patients as the initial strategy.
  3. Drug Choice: Rosuvastatin is a high-intensity statin appropriate for high-risk patients.
  4. Distractors:
    • Option A: Incorrect. Ignoring these risk factors would be negligence.
    • Option B: Incorrect. Lifestyle alone is for Low Risk or potentially Intermediate Risk patients. High-risk patients need pharmacotherapy.
    • Option D: CAC scoring is useful for Intermediate Risk patients where the decision to treat is unclear. This patient is clearly High Risk based on traditional risk factors.
    • Option E: Fibrates are indicated for severe hypertriglyceridemia (TG > 10 mmol/L) to prevent pancreatitis or as add-on for mixed dyslipidemia if targets aren’t met. His TG is only 2.1.

References

  1. Pearson, G. J., et al. (2021). 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Canadian Journal of Cardiology. Available at ccs.ca 
  2. Medical Council of Canada. (2023). MCCQE Part I Clinical Decision-Making and Multiple-Choice Questions Objectives.
  3. Anderson, T. J., et al. (2016). 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult.
  4. RxFiles. (2023). Lipid Lowering Agents Comparison Chart. 13th Edition.
  5. Toronto Notes 2024. Cardiology Chapter: Dyslipidemia.
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