Abstract
Background Inflammation is a causal risk factor for cardiovascular disease. While individuals with elevated levels of inflammation may benefit from targeted therapy, population-level stability of inflammation over time is poorly defined, as is the relationship between repeated measures of inflammatory markers and incident myocardial infarction. C-reactive protein (CRP) is among the best-established inflammatory markers. Objectives To examine (i) the stability of CRP over repeat measurements and (ii) the association between patterns of repeated CRP and rates of first-time myocardial infarction. Methods The relationship between baseline and repeat assessment of CRP was analyzed in 14,960 individuals from the UK Biobank without a diagnosed underlying inflammatory condition. The association between baseline and repeat CRP and first-time myocardial infarction was estimated using a Cox proportional hazards model. Results Among the analyzed cohort, median (IQR) age was 58 (52-63) years, 7,564 (51%) were female, and median (IQR) CRP was 1.1 (0.6-2.3) mg/L at baseline. Baseline and repeat CRP were correlated (Spearman rho 0.64) across a median (IQR) follow-up interval of 4.4 (3.7-4.9) years. Among the 10,566 (71%) individuals with non-elevated CRP (<2 mg/L) at baseline, 8,776 (83%) had non-elevated CRP at repeat, while among the 4,394 (29%) with elevated CRP at baseline, 3,127 (62%) had elevated CRP at repeat. Across median (IQR) follow-up 11.5 (11.4, 11.8) years after the repeat CRP measurement, 426 individuals (2.9%) sustained a first-time myocardial infarction. Relative to non-elevated CRP at baseline and repeat, elevated CRP at both baseline and repeat was associated with incident first-time myocardial infarction (HR = 1.66; 95% CI: 1.31-2.12; P = 3.1 × 10-5), while elevated CRP during only baseline or repeat measurement was not (P > 0.05). Conclusions Persistently elevated CRP was significantly associated with incident first-time myocardial infarction. This finding highlights the importance of repeated measurement of inflammatory markers for cardiovascular risk stratification.