Prevalence of clinically actionable hsCRP and implications for statin eligibility and residual ASCVD risk in the United States

Background/Introduction High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic inflammation and a recognized risk-enhancing factor in U.S. cholesterol guidelines, yet contemporary prevalence estimates and its implications for statin eligibility and residual risk are not well defined. Purpose To estimate the contemporary national prevalence of elevated hs-CRP in U.S. adults and evaluate its impact on statin eligibility and predicted residual ASCVD risk using current guideline frameworks. Methods We analyzed nationally representative data from NHANES 2015–2023, pooling all available cycles with hs-CRP measurement. Adults aged ≥18 years were included. Survey-weighted prevalence of hs-CRP ≥2 mg/L and weighted medians across demographic, socioeconomic, and clinical subgroups were estimated. Guideline-based statin eligibility was evaluated by incorporating hs-CRP ≥2 mg/L as a risk enhancer into the 2018 ACC/AHA framework, comparing PREVENT and Pooled Cohort Equations (PCE). Residual ASCVD risk was quantified by comparing mean predicted 10-year risk across hs-CRP strata (<2 vs ≥2 mg/L). Results Overall, 44.1% of U.S. adults -- 101.5 million individuals (95% CI, 96.2–106.7 million) -- had hs-CRP ≥2 mg/L. Prevalence was higher in women (49.2%; 95% CI, 47.3–51.0%) than men (38.7%; 95% CI 37.0–40.3%), and highest among non-Hispanic Black adults (50.0%; 95% CI 47.8–52.2%). Median hs-CRP increased stepwise with worsening cardiometabolic status: from 0.75 mg/L (95% CI, 0.70–0.79) in normal-weight adults to 5.50 mg/L (95% CI, 5.33–5.84) in class III obesity, from 1.63 mg/L (95% CI, 1.541.74) at eGFR ≥90 to 3.32 mg/L (95% CI, 1.49–4.49) at eGFR <15, and from 1.38 mg/L (95% CI, 1.31–1.46) at HbA1c <5.7% to 3.34 mg/L (95% CI, 2.97–3.98) at HbA1c ≥8. Incorporating hs-CRP ≥2 mg/L as a risk enhancer upgraded the strength of guideline recommendations for statin therapy for ~20 million adults -- 19.8 million (95% CI, 17.8–21.9 million) using PREVENT and 23.3 million (95% CI, 20.9–25.6 million) using PCE. Predicted 10-year ASCVD risk was consistently higher among those with hs-CRP ≥2 mg/L compared to hs-CRP<2 mg/L, at 3.9% (3.7-4.0%) vs 3.1% (3.0-3.3%) with PREVENT and 9.4% (9.1-9.8%) vs 8.4% (7.8-9.0%) with PCE in the overall population. Conclusions Nearly half of U.S. adults, approximately 102 million individuals, have clinically actionable inflammation defined by hs-CRP ≥2 mg/L. hs-CRP levels increase progressively with obesity class, impaired kidney function, and poor glycemic control. Incorporating hs-CRP as a risk enhancer upgrades the strength of statin guideline recommendations for approximately 20 million adults and reveals residual risk beyond conventional ASCVD risk calculators, underscoring systemic inflammation as a prevalent and actionable determinant of preventive care.