Lab Update 22 – Update of LDL-Cholesterol

March 2021
Dr Boitumelo Phiri – Chemical Pathologist
Ampath | ampath.co.za

Why Focus on LDL-Cholesterol?

• LDL-C (low-density lipoprotein cholesterol) is central to the development and treatment of atherosclerosis.
• Retention of LDL-C and other ApoB-containing lipoproteins in the artery wall initiates the atherosclerotic process.
• Clinical trials confirm that lowering LDL-C reduces cardiovascular (CV) events.
• There is no lower limit of LDL-C below which benefit is lost or harm occurs.
• PCSK-9 inhibitors can lower LDL-C by ~60% and have shown safety even at very low levels.

New LDL-C Target Guidelines (2021)

Based on:

• 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines
• Adopted in South Africa by:
  • Lipid and Atherosclerosis Society of Southern Africa (LASSA)
  • South African Heart Association

Updated LDL-C Targets by Cardiovascular Risk

1. Very High Risk

• Previous target: <1.8 mmol/L
• New target:
  • LDL-C reduction ≥50% from baseline
  • AND LDL-C <1.4 mmol/L
  • For patients with a second vascular event within 2 years: LDL-C <1.0 mmol/L

2. High Risk

• Previous target: <2.5 mmol/L
• New target:
  • LDL-C reduction ≥50% from baseline
  • AND LDL-C <1.8 mmol/L

3. Moderate Risk

• Previous target: <3.0 mmol/L
• New target:
  • LDL-C <2.6 mmol/L

4. Low Risk

• Target remains: LDL-C <3.0 mmol/L

Cardiovascular Risk Stratification Categories

Category 1: Very High Risk

(Patients who should not be scored; they are already classified)

• Documented atherosclerotic cardiovascular disease (ASCVD), including:
  • Acute coronary syndrome (ACS)
  • Myocardial infarction
  • Stroke
  • Peripheral arterial disease (PAD)
• Diabetes with:
  • Target organ damage
  • OR three or more major risk factors
• Type 1 diabetes of more than 40 years’ duration
• Severe chronic kidney disease (GFR <30 mL/min/1.73 m²)
• Familial hypercholesterolaemia (FH) with ASCVD or another major risk factor
• Imaging evidence of significant plaque (e.g., via carotid ultrasound, coronary calcium score)

Category 2: High Risk

(Patients who also don’t require scoring)

• Severe single risk factor such as:
  • LDL-C >4.9 mmol/L
  • Total cholesterol >8.0 mmol/L
  • Blood pressure ≥180/110 mmHg
• FH without other major risk factors
• Diabetes (without organ damage), of ≥10 years' duration, or with at least one additional risk factor
• Chronic kidney disease with GFR 30–59 mL/min/1.73 m²

Category 3: Score-Based Risk

(Use Framingham Risk Score)

• Calculate using age, sex, total cholesterol, HDL-C, systolic BP, and smoking status
• Risk groups:
  • Very high: >30%
  • High: 15–30%
  • Moderate: 3–15%
  • Low: <3%

Recommended LDL-C Treatment Strategy

For Very High Risk Patients

• Target LDL-C:
  • ≥50% reduction from baseline
  • AND <1.4 mmol/L
  • <1.0 mmol/L if second event in 2 years
• Non-HDL-C goal: <2.2 mmol/L
• Treatment:
  • Initiate lifestyle changes
  • Start statin
  • Add ezetimibe if needed
  • Add PCSK-9 inhibitor if not at target

For High Risk Patients

• Target LDL-C:
  • ≥50% reduction from baseline
  • AND <1.8 mmol/L
• Non-HDL-C goal: <2.6 mmol/L
• Treatment:
  • Lifestyle + statin
  • Add ezetimibe or PCSK-9 inhibitor as needed

For Moderate and Low Risk Patients

• Targets:
  • Moderate: LDL-C <2.6 mmol/L
  • Low: LDL-C <3.0 mmol/L
• Treatment usually starts with lifestyle modification
• Consider medication only if risk factors are significant or goals are not achieved

PCSK-9 Inhibitor Indications

Add a PCSK-9 inhibitor if, despite maximum tolerated statin and ezetimibe, the patient is:

• At very high risk with persistent LDL-C elevation
• A post-acute coronary syndrome (ACS) patient not reaching target after 4–6 weeks
• A patient with familial hypercholesterolaemia (FH) at high or very high risk

LDL-C Baseline Definition

• Either:
  • LDL-C measured before starting therapy
  • OR estimated retrospectively if not previously recorded

Abbreviations

• ASCVD: Atherosclerotic cardiovascular disease
• ACS: Acute coronary syndrome
• TIA: Transient ischaemic attack
• DM: Diabetes mellitus
• FH: Familial hypercholesterolaemia
• CKD: Chronic kidney disease
• GFR: Glomerular filtration rate
• LDL-C: Low-density lipoprotein cholesterol
• HDL-C: High-density lipoprotein cholesterol
• PCSK-9: Proprotein convertase subtilisin/kexin type 9

References

1. South African Dyslipidaemia Guideline Consensus Statement. SAMJ, 2018
2. ESC/EAS Lipid Guidelines. European Heart Journal, 2020
3. Klug EQ & Raal FJ. SAMJ, 2020

📌 For help with cardiovascular risk assessment or lipid management, please contact your local Ampath pathologist.