title: Baseline and long-term fibrinogen levels and risk of sudden cardiac death: A new prospective study and meta-analysis.
abstract: BACKGROUND
  Inflammatory markers such as C-reactive protein (CRP) and interleukin-6 have been linked with an increased risk of sudden cardiac death (SCD), but the relationship between fibrinogen and SCD is uncertain. We aimed to assess the association between fibrinogen and SCD.
  
  
  METHODS
  Plasma fibrinogen was measured at baseline in a prospective cohort of 1773 men aged 42-61 years free of heart failure or cardiac arrhythmias, that recorded 131 SCDs during 22 years follow-up. Correction for within-person fibrinogen variability was made using data from repeat measurements taken several years apart.
  
  
  RESULTS
  Fibrinogen was strongly correlated with CRP, weakly correlated with several cardiovascular risk markers, and was log-linearly associated with SCD risk. In analyses adjusted for conventional risk factors, the hazard ratio (HR) (95% CIs) for SCD per 1 standard deviation (SD) higher baseline loge fibrinogen was 1.32 (1.11-1.57). The results remained consistent on further adjustment for alcohol consumption, resting heart rate, and circulating lipids 1.30 (1.09-1.56). The corresponding HRs were 1.80 (1.25-2.58) and 1.74 (1.20-2.52) after correction for within-person variability. HRs remained unchanged on further adjustment for CRP and accounting for incident coronary events. In a meta-analysis of three cohort studies, the fully-adjusted relative risks for SCD per 1 SD higher baseline and long-term fibrinogen levels were 1.42 (1.25-1.61) and 2.07 (1.59-2.69) respectively. The associations were similar for non-SCDs in both cohort analysis and the meta-analysis. Addition of plasma fibrinogen to a SCD risk prediction model containing established risk factors did not significantly improve risk discrimination, but improved the net reclassification.
  
  
  CONCLUSIONS
  Available data suggest fibrinogen is positively, log-linearly, and independently associated with risk of SCD. Further research is needed to assess the potential relevance of plasma fibrinogen concentrations in SCD prevention.
authors.affiliation: School of Clinical Sciences, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Southmead Road, Bristol, UK. Electronic address: skk31@cantab.net.
authors.forename: Setor K
authors.initials: SK
authors.lastname: Kunutsor
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kurl
authors.affiliation: Diabetes Research Centre, University of Leicester, Leicester, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Jari A
authors.initials: JA
authors.lastname: Laukkanen
mesh_terms: D015415:Biomarkers / Q000097:blood; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D005340:Fibrinogen / Q000032:analysis*; D014943:Global Health; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000401:mortality; D006801:Humans; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005340:Fibrinogen
keywords: Fibrinogen; Inflammation; Non-sudden cardiac death; Regression dilution; Sudden cardiac death