Triple-Biomarker Risk Pathway ( LDL + hs-CRP + Lp(a))
Triple-Biomarker Risk Pathway ( LDL + hs-CRP + Lp(a))
Medical News Summary, based on an article published in the 2025 European Heart Journal (doi:10.1093/eurheartj/ehaf209)
1) Who to test (one-time “triple test”)
1. Primary prevention: Adults 30–75 at borderline/intermediate risk, risk-enhancing factors, family history of premature ASCVD, or uncertainty after standard calculators.
2. Secondary prevention: All patients with established ASCVD (for residual inflammatory or thrombotic risk profiling).
2) How to measure & interpret
1. LDL : Standard fasting/non-fasting lab; treat to targets (see Actions below).
2. hs-CRP:
• Measure twice, ≥2 weeks apart, when clinically well (no infection/trauma).
• Cut-points: ≥2 mg/L = elevated (residual inflammatory risk). ≥10 mg/L → search for non-CV inflammatory causes, repeat when well.
3. Lp(a):
• Once-in-a-lifetime test (genetically fixed).
• High: ≥125 nmol/L (≈ ≥50 mg/dL)*; Intermediate: 30–124 nmol/L; Low: <30 nmol/L.
• Consider cascade screening of first-degree relatives if high.
*Conversion mg/dL↔️nmol/L varies by assay; use lab-reported reference.
3) Combine results into a simple risk tier
Count how many are “elevated”: LDL above goal, hs-CRP ≥2 mg/L, Lp(a) ≥125 nmol/L.
4) Practical action steps
A) LDL–centered (both primary & secondary)
1. High-intensity statin to reach goal.
2. If above goal: add ezetimibe → PCSK9 inhibitor (or bempedoic acid if statin-intolerant/adjunct).
3. Targets (choose per guideline you follow):
• Very-high risk: LDL-C <55 mg/dL (ESC) or <70 mg/dL (ACC).
• Consider apoB (<65 mg/dL very-high risk) where available.
B)Inflammation-centered (hs-CRP ≥2 mg/L after LDL at goal)
1. First line: Lifestyle “bundle” (weight loss, Mediterranean-style diet, exercise, smoking cessation, sleep, periodontal care, vaccines).
2. Drug options (select patients):
• Colchicine 0.5 mg daily (secondary prevention; avoid in significant CKD/hepatic disease, drug interactions; counsel on GI effects).
• Bempedoic acid lowers LDL and hs-CRP (useful in statin intolerance or as add-on).
C) Lp(a)–centered
1. If Lp(a) ≥125 nmol/L (≈ ≥50 mg/dL):
• Tight LDL control (often lower than usual targets).
• Consider PCSK9 inhibitor (modest Lp(a) lowering; outcome benefit driven largely by LDL reduction).
• Family screening; discuss trial eligibility for antisense/siRNA Lp(a) agents where available.
D) Role of CAC (primary prevention)
• Use CAC when treatment decisions remain uncertain.
• CAC=0: consider de-escalation (except smokers, diabetes, strong FH).
• CAC≥100 (or ≥75th percentile): favors statins and tighter control regardless of hs-CRP.
5) One-page takeaway (Doctor’s talking points )
1. Order LDL-C + hs-CRP (×2) + Lp(a) once.
2. Treat LDL-C to goal (statin ± ezetimibe ± PCSK9i / bempedoic).
3. If hs-CRP ≥2 mg/L despite LDL at goal → lifestyle first, then consider colchicine (secondary prevention).
4. If Lp(a) high → tighten LDL-C goal, PCSK9i as needed, family screening.
5. Use CAC when primary-prevention decisions are uncertain.
6. Re-check lipids at 4–12 weeks; hs-CRP once to confirm; don’t repeat Lp(a).
