Factors Associated with Elevated High-Sensitivity C-Reactive Protein Levels in Individuals with Atherosclerotic Cardiovascular Disease in the US and the UK

Aim Novel therapies are under evaluation for upstream inhibition of inflammatory pathways in atherosclerotic cardiovascular disease (ASCVD). Elevated high-sensitivity C-reactive protein (hsCRP) is a downstream marker of these pathways but is not routinely measured. We aimed to identify potential factors associated with elevated hsCRP. Methods This cross-sectional study included individuals with ASCVD from the UK Biobank (2006-2010) and the US National Health and Nutrition Examination Survey (NHANES; 1999-2010 and 2015-2018). Factors associated with elevated hsCRP (2-10 mg/L) were evaluated using multivariable logistic regression. Results Six factors were associated with greater odds of elevated hsCRP in both cohorts (UK Biobank n = 23,045; NHANES n = 3,415): obesity (UK Biobank odds ratio [OR] [95% confidence interval (CI)]: 3.48 [3.18-3.80]); NHANES 4.11 [2.66-6.34]), overweight (1.56 [1.44-1.70]; 2.26 [1.51-3.38]), being a current smoker (2.47 [2.27-2.69]; 1.96 [1.23-3.10]), female sex (1.69 [1.59-1.80]; 1.69 [1.24-2.31]), and increased low-density lipoprotein cholesterol (1.05 [1.04-1.06]; 1.00 [1.00-1.00], per 10 mg/dL increase) and triglyceride levels (1.01 [1.01–1.01]; 1.00 [1.00-1.00], per 10 mg/dL increase) (all p <0.05). Receiving statins was associated with lower odds in both cohorts (UK Biobank OR [95% CI] 0.69 [0.64-0.75]; NHANES 0.54 [0.39-0.74]). When these factors, plus chronic kidney disease stage G3-5, were considered in combination, hsCRP levels were higher in individuals with more factors (median hsCRP with seven factors: UK Biobank 5.39 mg/L; NHANES 6.99 mg/L). Conclusions The factors identified may support data-driven targeted testing to identify those most likely to have elevated hsCRP, who could potentially benefit from emerging anti-inflammatory therapies.