title: Non-linear contribution of glucose measures to cardiovascular diseases and mortality: reclassifying the Framingham's risk categories: a decade follow-up from the Tehran lipid and glucose study.
abstract: BACKGROUND
  We investigated non-linear contribution of fasting plasma glucose (FPG) and 2-hour post-challenge plasma glucose (2h-PCPG) to the risk of CVD and mortality. We hypothesized that glucose measures improve risk-stratification made by the Framingham's general CVD risk algorithm.
  
  
  METHODS
  Among participants aged ≥ 30 (n=8071), not taking glucose-lowering agents, 6169 (3477 women) remained eligible. Non-linear contribution of FPG and 2h-PCPG to incident CVD and mortality were assessed using Cox models incorporating restricted cubic splines functions. Risk reclassification improvement conferred by FPG and 2h-PCPG was examined using an extended version of net reclassification index (NRI) that takes into account the censoring nature of survival data.
  
  
  RESULTS
  We documented 465 incident CVD events (402 CHD), 212 deaths from any cause (94 CVD deaths). Excluding the contribution of the 2h-PCGP to mortality (that was linear) dose-response relationships between glucose measures and CVD and mortality were curvilinear with nadirs below which decreasing levels of glucose were unlikely to offer any benefit. These nadirs were assigned to FPG of 4.9-5.3 and 2h-PCPG of 6.0 mmol.l(-1). Glucose measures added to the predictive ability of the Framingham's general CVD risk algorithm with cutpoint-free NRIs ranging from 19 to 54%.
  
  
  CONCLUSIONS
  Glucose measures contributed to the risk of CVD and mortality in a curvilinear fashion, we observed increased risk below glucose thresholds currently used to define diabetes, supporting criteria for the diagnosis of impaired fasting glycemia and impaired glucose tolerance. Glucose measures were observed to add to predictive ability of the predictive model which included established cardiovascular risk factors.
authors.affiliation: Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Homa
authors.initials: H
authors.lastname: Yadegari
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Bozorgmanesh
authors.forename: Farzad
authors.initials: F
authors.lastname: Hadaegh
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Azizi
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D008055:Lipids