title: Is hypoglycaemia a marker for increased long-term mortality risk in patients with coronary artery disease? An 8-year follow-up.
abstract: BACKGROUND
  No information is available regarding the association between low plasma glucose levels and cause-specific and all-cause mortality in patients with coronary artery disease (CAD). We aimed to investigate the relationship between hypoglycaemia and all-cause, cardiovascular and cancer mortality in a large population of patients with CAD.
  
  
  METHODS
  Patients were recruited from the BIP (Bezafibrate Infarction Prevention) registry, a secondary prevention prospective multicentre randomized, placebo-controlled, double-blind trial aimed to assess the efficacy of bezafibrate in reduction of coronary events.
  
  
  METHODS
  The study included 14,670 CAD patients aged 45-74, divided into six groups: (1) hypoglycaemic (up to 69 mg/dl); (2) low normal (70-79 mg/dl); (3) euglycaemic (80-109 mg/dl); (4) impaired fasting glucose (IFG) (110-125 mg/dl); (5) borderline diabetics (126-139 mg/dl); (6) diabetics (> or 140 mg/dl).
  
  
  RESULTS
  Patients comprised 131 with hypoglycaemia (0.9%), 731 with low normal glucose (5%), 9308 euglycaemic (63.4%), 1577 with IFG (10.7%), 617 borderline diabetics (4.2%) and 2306 diabetics (15.7%). Over a mean 8-year follow-up, crude all-cause mortality was higher in both diabetic (31.8%) and hypoglycaemic groups (25.2%) as compared with euglycaemics (14.9%; P<0.0001); CAD mortality was higher in diabetic and borderline groups (17.8 and 13.3%, respectively, versus 7.9% in euglycaemics; P<0.0001). The highest prevalence of cancer mortality was documented in the hypoglycaemic group (6.1 versus 2.9% in euglycaemics; P<0.02). Actuarial survival curves showed the lowest mortality in euglycaemic and low normal groups; the highest was seen in diabetic and hypoglycaemic patients. Intermediate values were found in borderline and IFG patients. After adjustment for variables, a significantly higher mortality rate was seen in hypoglycaemics when compared with euglycaemics (P<0.0001). Hypoglycaemia was identified as a predictor of increased all-cause and cancer mortality with a hazard ratio (HR) of 1.84 [95% confidence interval (CI) 1.29-2.61] and 2.26 (95% CI 1.12-4.57), respectively, but not of increased CAD mortality, with HR 1.30 (95% CI 0.73-2.29).
  
  
  CONCLUSIONS
  Over a mean 8-year follow-up, hypoglycaemia emerges as a marker for substantially increased all-cause and cancer mortality among patients with CAD presenting with low fasting glucose levels.
authors.affiliation: Cardiac Rehabilitation Institute, Chaim Medical Center, Tel-Hashomer, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. zfisman@post.tau.ac.il
authors.forename: Enrique Z
authors.initials: EZ
authors.lastname: Fisman
authors.forename: Michael
authors.initials: M
authors.lastname: Motro
authors.forename: Alexander
authors.initials: A
authors.lastname: Tenenbaum
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
authors.forename: Valentina
authors.initials: V
authors.lastname: Boyko
authors.forename: Lori
authors.initials: L
authors.lastname: Mandelzweig
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Sherer
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Adler
authors.forename: Solomon
authors.initials: S
authors.lastname: Behar
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007003:Hypoglycemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000401:mortality*; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors
chemical_list: D001786:Blood Glucose