Lipid Update: Changes to South African Dyslipidaemia Guidelines (2018) & New Markers for Assessing Lipid Status

PATHCHAT Edition No. 61
October 2019
Please contact your local Ampath pathologist for more information.

Author: Dr. Boitumelo Phiri-Ramongane, Chemical Pathologist

Introduction

✅ Guideline Updates

• The 2018 South African Dyslipidaemia Guidelines align with the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines.
• Updated recommendations improve cardiovascular disease (CVD) risk assessment and lipid management.

📌 These changes promote evidence-based dyslipidaemia management in South Africa.

Screening for Dyslipidaemia

✅ Revised Recommended Age for Screening:

• 40 years for individuals without cardiovascular risk factors.
• Earlier screening for individuals with genetic risk or comorbid conditions.

🔹 Recommended Age of Screening Based on Risk Factors:

✔ From 8 Years of Age (Early Screening Required):

• Family history of severe dyslipidaemia.
• Relative of a patient with familial hypercholesterolaemia (FH).
• Infants should be screened before 6 months if both parents have FH.

✔ From 20 Years of Age (Intermediate Risk Individuals):

• Hypertension or use of antihypertensive medication.
• Any smoking history.
• Family history of premature cardiovascular disease (CVD) (males ≤55 years, females ≤65 years).
• BMI ≥30 kg/m² or waist circumference >94 cm (men) or >80 cm (women).
• Chronic inflammatory diseases (e.g., rheumatoid arthritis, lupus, psoriasis).
• Chronic kidney disease (CKD).

✔ From 40 Years of Age (General Population):

• All other asymptomatic adults without evidence of CVD, diabetes, CKD, or FH.

📌 Early screening improves early detection and prevention of cardiovascular complications.

Lipid Testing Recommendations

✅ 1. Timing of Lipid Testing at Diagnosis

• Traditionally, a 12-hour fasting lipogram (total cholesterol [TC], LDL-C, HDL-C, triglycerides [TG]) was required.
• New evidence shows non-fasting lipograms provide similar results and improve compliance.

🔹 Non-Fasting Lipid Testing is Acceptable Unless:

• Triglycerides >4 mmol/L in a random sample.
• Non-HDL cholesterol >5.7 mmol/L.
• Fasting lipid tests remain necessary for certain genetic and secondary hypertriglyceridaemias.

📌 Non-fasting lipid testing is now preferred unless specific conditions require fasting samples.

Evaluation of Lipid & Apolipoprotein Parameters

✅ 1. Non-HDL Cholesterol

• Calculated as Total Cholesterol (TC) – HDL-C.
• Represents the total number of atherogenic particles in plasma (LDL, VLDL, IDL, and Lp(a)).
• More predictive than LDL-C in diabetes, metabolic syndrome, and CKD.

🔹 Recommended Non-HDL-C Targets:

• Very high-risk patients: <2.6 mmol/L
• High-risk patients: <3.3 mmol/L

📌 Non-HDL-C is an alternative marker when LDL-C does not fully capture risk.

✅ 2. TC/HDL & LDL/HDL Cholesterol Ratios

• TC/HDL-C Ratio ≥3.5 is linked to metabolic syndrome and CVD risk.
• These ratios provide better risk stratification than individual lipid values.
• Canada uses the TC/HDL-C ratio as a secondary therapeutic target.

📌 These ratios are simple yet effective markers of atherogenic dyslipidaemia.

✅ 3. Triglyceride/HDL-C Ratio

• Associated with insulin resistance and atherogenic dyslipidaemia.
• Higher ratios indicate increased cardiovascular risk.
• Clinical application is still being evaluated.

📌 A high TG/HDL ratio is strongly linked to coronary artery disease and severity of insulin resistance.

✅ 4. Apo B/Apo A1 Ratio

• Apolipoprotein B (Apo B) represents atherogenic particles (LDL, VLDL, IDL).
• Apolipoprotein A1 (Apo A1) represents anti-atherogenic HDL.
• A high Apo B/Apo A1 ratio reflects increased CVD risk.

📌 This ratio has been used in studies as a cardiovascular risk marker but is not yet a treatment target.

Emerging Lipid Biomarkers

✅ 1. Small Dense LDL-C (sdLDL-C)

• Highly atherogenic due to prolonged circulation and susceptibility to oxidation.
• Associated with metabolic syndrome, diabetes, and cardiovascular events.
• Predicts CVD risk even in patients with low LDL-C.

🔹 Clinical Application:

• sdLDL >0.90 mmol/L indicates higher cardiovascular risk.

📌 sdLDL-C improves risk stratification in patients with normal lipid levels.

✅ 2. Oxidised LDL (Ox-LDL)

• Oxidation of LDL plays a key role in atherosclerosis.
• Ox-LDL levels correlate with coronary artery disease severity.

🔹 Studies on Ox-LDL & CVD Risk:

• Elevated Ox-LDL is seen in acute coronary syndromes.
• Predicts CVD events independent of LDL-C levels.
• Linked to inflammation in autoimmune diseases and CKD.

📌 Ox-LDL is being evaluated as a novel biomarker for residual cardiovascular risk.

✅ 3. Residual Cardiovascular Risk

• Up to 50% of patients with coronary artery disease (CAD) achieve LDL-C targets but still have events.
• Residual risk may be due to:
  • Small dense LDL.
  • Oxidised LDL.
  • Inflammation markers.
  • Lipoprotein(a) [Lp(a)].

📌 Statin therapy alone may not fully mitigate CVD risk—additional lipid markers are being explored.

Assessment of Treatment Goals & Monitoring

✅ Recommended Testing Frequency:

• 6-month lipid testing after lifestyle modification alone.
• 8-week lipid testing after initiating or changing lipid-lowering therapy.
• 6-monthly testing in patients at target.

📌 Regular monitoring ensures optimal lipid control and CVD prevention.

Genetic Testing for Familial Hypercholesterolaemia (FH)

✅ Upcoming Ampath Genetic Panel for FH:

• Detects mutations in:
  • LDL receptor gene (LDLR).
  • Apolipoprotein B gene (APOB).
  • Proprotein convertase subtilisin/kexin Type 9 (PCSK9) gene.

✅ Who Should Be Tested?

• Cascade screening in relatives of patients with FH.
• Patients with LDL-C ≥7.5 mmol/L.

📌 Genetic testing helps identify at-risk individuals and enables early intervention.

Key Takeaways for Clinicians

✅ Non-fasting lipid testing is now preferred unless specific indications require fasting.
✅ Non-HDL-C and lipid ratios improve risk prediction in metabolic syndrome and diabetes.
✅ Small dense LDL and oxidised LDL may provide insight into residual cardiovascular risk.
✅ Genetic testing for FH is becoming an essential tool for early detection and treatment.

📌 Advancements in lipid markers enhance cardiovascular risk assessment beyond traditional lipids.