title: Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: insights from the National Health and Nutrition Examination Survey-III.
abstract: BACKGROUND
  Neutrophil lymphocyte ratio (NLR) has been shown to predict cardiovascular events in several studies. We sought to study if NLR predicts coronary heart disease (CHD) in a healthy US cohort and if it reclassifies the traditional Framingham risk score (FRS) model.
  
  
  METHODS
  We performed post hoc analysis of National Health and Nutrition Examination Survey-III (1998-94) including subjects aged 30-79 years free from CHD or CHD equivalent at baseline. Primary endpoint was death from ischemic heart disease. NLR was divided into four categories: <1.5, ≥1.5 to <3.0, 3.0-4.5 and >4.5. Statistical analyses involved multivariate Cox proportional hazards models as well as discrimination, calibration and reclassification.
  
  
  RESULTS
  We included 7363 subjects with a mean follow up of 14.1 years. There were 231 (3.1%) CHD deaths, more in those with NLR>4.5 (11%) compared to NLR<1.5 (2.4%), p<0.001. Adjusted hazard ratio of NLR>4.5 was 2.68 (95% CI 1.07-6.72, p=0.035). There was no significant improvement in C-index (0.8709 to 0.8713) or area under curve (0.8520 to 0.8531) with addition of NLR to FRS model. Model with NLR was well calibrated with Hosmer-Lemeshow chi-square of 8.57 (p=0.38). Overall net reclassification index (NRI) was 6.6% (p=0.003) with intermediate NRI of 10.1% (p<0.001) and net upward reclassification of 5.6%. Absolute integrated discrimination index (IDI) was 0.003 (p=0.039) with relative IDI of 4.3%.
  
  
  CONCLUSIONS
  NLR can independently predict CHD mortality in an asymptomatic general population cohort. It reclassifies intermediate risk category of FRS, with significant upward reclassification. NLR should be considered as an inflammatory biomarker of CHD.
authors.affiliation: Department of Medicine, Staten Island University Hospital, Staten Island, NY, United States. Electronic address: neerajshah86@gmail.com.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Cardiology, Staten Island University Hospital, Staten Island, NY, United States.
authors.forename: Valay
authors.initials: V
authors.lastname: Parikh
authors.affiliation: Department of Medicine, Staten Island University Hospital, Staten Island, NY, United States.
authors.forename: Nileshkumar
authors.initials: N
authors.lastname: Patel
authors.affiliation: Heart & Vascular Institute, Detroit Medical Center, Detroit, MI, United States.
authors.forename: Nilay
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Cardiology, Wayne State University School of Medicine, Detroit, MI, United States.
authors.forename: Apurva
authors.initials: A
authors.lastname: Badheka
authors.affiliation: Department of Cardiology, University of Arkansas for Medical Science, Little Rock, AR, United States.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Deshmukh
authors.affiliation: Department of Cardiology, Cedars Sinai Medical Center, Los Angeles, CA, United States.
authors.forename: Ankit
authors.initials: A
authors.lastname: Rathod
authors.affiliation: Department of Cardiology, Staten Island University Hospital, Staten Island, NY, United States.
authors.forename: James
authors.initials: J
authors.lastname: Lafferty
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D009749:Nutrition Surveys / Q000379:methods*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Coronary heart disease (CHD); Framingham risk score (FRS); Neutrophil lymphocyte ratio (NLR); Reclassification