Residual Cardiovascular Risk Factors

PATHCHAT Edition No. 75
2021
Please contact your local Ampath pathologist for more information.

Author:

• Dr. Boitumelo Phiri (Chemical Pathologist)

Introduction

✅ Understanding Residual Cardiovascular Risk

• Despite advancements in managing cardiovascular disease (CVD), many patients continue to experience vascular events.
• Primary strategies focus on managing traditional risk factors:
  • Dyslipidaemia.
  • Hypertension.
  • Hyperglycaemia.
  • Inflammation.
  • Lifestyle factors.
• LDL-C reduction with statins remains the cornerstone of therapy.
• However, many patients on statins fail to reach target LDL-C levels, leading to “residual cardiovascular risk” (RCVR).

📌 RCVR refers to the persistent risk of vascular damage despite optimal treatment of traditional risk factors.

Dyslipidaemia Post-Statin Treatment

✅ Lipid-Related Residual Risk

• Statins reduce cardiovascular risk by 25–35%.
• High-dose statins and combination therapies provide further risk reduction.
• However, statins do not significantly address non-LDL-C lipid abnormalities.

📌 Residual lipid risk remains a challenge despite statin therapy.

Atherogenic Markers in Residual Cardiovascular Risk

✅ 1. Non-HDL Cholesterol & Apolipoprotein B (ApoB)

• Non-HDL-C includes all atherogenic particles (LDL, VLDL, IDL, Lp(a)).
• ApoB is a structural protein found in all atherogenic lipoproteins.
• ApoB levels better predict cardiovascular risk than LDL-C alone.

✅ 2. Lipoprotein(a) (Lp(a))

• Lp(a) consists of an LDL-like particle attached to apolipoprotein(a).
• Elevated Lp(a) levels increase thrombosis risk by interfering with fibrinolysis.
• European guidelines recommend measuring Lp(a) once in adulthood.

📌 High ApoB and Lp(a) levels are independent predictors of cardiovascular risk in statin-treated patients.

Residual Metabolic Risk

✅ Atherogenic Dyslipidaemia (AD) & Cardiovascular Risk

• AD is characterised by:
  • Low HDL-C.
  • High fasting triglycerides (TG).
• Common in diabetes and metabolic syndrome.
• Studies show AD increases cardiovascular risk even in patients with well-controlled LDL-C.

📌 Addressing AD can further reduce cardiovascular events.

Inflammation & Cardiovascular Risk

✅ 1. High-Sensitivity C-Reactive Protein (hs-CRP)

• Hs-CRP is a marker of chronic vascular inflammation.
• Levels correlate with cardiovascular disease risk:
  • Low risk: <1 mg/L.
  • Moderate risk: 1–3 mg/L.
  • High risk: >3 mg/L.
• Elevated hs-CRP levels predict residual cardiovascular risk in statin-treated patients.

✅ 2. Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)

• Lp-PLA2 is an enzyme linked to LDL and involved in vascular inflammation.
• High levels indicate unstable, rupture-prone plaques.
• Patients with elevated Lp-PLA2 are at increased risk for cardiovascular events.

📌 Inflammation plays a key role in residual cardiovascular risk beyond lipid control.

Clinical Implications & Recommendations

✅ Key Laboratory Tests for Residual Cardiovascular Risk Assessment:

1. ApoB (Measures total atherogenic lipoproteins).
2. Lp(a) (Assesses genetic cardiovascular risk).
3. Non-HDL-C (Better predictor of CVD risk than LDL-C alone).
4. Hs-CRP (Identifies residual inflammatory risk).
5. Lp-PLA2 (Detects rupture-prone plaques).

✅ Recommended Targets Based on Residual Risk Factors:

• LDL-C <1.8 mmol/L (very high risk patients).
• Non-HDL-C <2.5 mmol/L (very high risk patients).
• ApoB <65 mg/dL (very high risk patients).
• Lp(a) measurement recommended once in adulthood.
• Hs-CRP <1 mg/L for lowest cardiovascular risk.
• Lp-PLA2 <200 ng/mL suggests lower plaque instability risk.

📌 Monitoring these markers can guide more personalized cardiovascular risk management.

Key Takeaways for Clinicians

✅ Traditional lipid management strategies do not fully eliminate cardiovascular risk.
✅ ApoB and non-HDL-C better reflect total atherogenic burden than LDL-C alone.
✅ Lp(a) is a strong predictor of cardiovascular disease and should be measured at least once in adulthood.
✅ Elevated hs-CRP and Lp-PLA2 levels indicate residual inflammatory risk.
✅ Targeting metabolic and inflammatory residual risks can further reduce cardiovascular events.

📌 Comprehensive lipid and inflammation assessments are critical for optimal cardiovascular disease prevention and management.