Optimizing long-term cardiovascular risk stratification: incorporating biomarkers into the atherosclerotic cardiovascular disease very high-risk definition

Background The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline defines very high-risk (VHR) atherosclerotic cardiovascular disease (ASCVD) patients to guide intensive lipid-lowering therapy. Objectives This study sought to evaluate VHR’s effectiveness in assessing cardiovascular (CV) risk in an Asian population and examine the predictive value of additional biomarkers for improving risk stratification. Methods 26,752 ASCVD patients were prospectively enrolled (2017–2018). VHR was defined as multiple major ASCVD events or one major event with multiple high-risk conditions. The primary outcome was a composite of 3-year CV events, including cardiovascular mortality, myocardial infarction, stroke, and coronary revascularization. Results 14,475 (54.1%) patients were classified as VHR, with higher 3-year event rates than non-VHR (9.6% vs. 7.3%). Hemoglobin (Hb), high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) (Lp(a)), and high-density lipoprotein cholesterol (HDL-C) were significant CV risk influencers in VHR patients (hazard ratios [95% CI]: 0.93 [0.90–0.96], 1.13 [1.06–1.21], 1.07 [1.04–1.11], 0.73 [0.61–0.89], respectively), but not in non-VHR patients. Within the VHR category, patients with ≥2 abnormal biomarkers (Hb <12 g/dL for men, <11 g/dL for women; hs-CRP >3 mg/L; Lp(a) ≥50 mg/dL; HDL-C <1 mmol/L) were categorized as Very Very High Risk (VVHR), showing significantly higher event rates than those with fewer abnormal biomarkers (11.7% vs. 8.9%, P < 0.001). Conclusions The VHR definition effectively identifies high-risk Asian patients but can be refined by integrating biomarker-based high-risk conditions. The proposed VVHR category enhances risk stratification, identifying those who may benefit most from intensive lipid-lowering and residual risk management.