Abstract

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30–79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87–0.93) and 3.01 g/L (2.98–3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44–1.94) for MCE and 1.22 (1.10–1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.

Highlights

  • Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear

  • We examined the associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS), and intracerebral hemorrhage (ICH) in a nested case-control study, set within the prospective China Kadoorie Biobank (CKB)

  • In this large nested case-control study of Chinese adults, who have low mean low-density lipoprotein cholesterol (LDL-C) (~92 mg/dL), CRP was positively associated with risks of incident MCE, IS, and ICH, independent of established risk factors

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Summary

Introduction

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Reliable assessment of the association of systemic inflammation with stroke types is important in China, where stroke rates are much higher than for Western populations, for ICH28, in spite of relatively low mean LDL-C levels (~92 mg/dL). To address these questions, we examined the associations of CRP and fibrinogen with risks of incident major coronary events (MCE), IS, and ICH in a nested case-control study, set within the prospective China Kadoorie Biobank (CKB)

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