title: Plasma lipid transfer proteins and cardiovascular disease. The Framingham Heart Study.
abstract: OBJECTIVE
  Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are two genetically-related plasma proteins involved in the exchange of cholesteryl esters and phospholipids between high-density lipoproteins (HDL) and other lipoproteins. Although low CETP and high PLTP activity both result in higher concentrations of plasma HDL-cholesterol (HDL-C), there is no evidence that either of these changes is associated with a decrease in cardiovascular disease (CVD) in a general population.
  
  
  METHODS
  Plasma CETP and PLTP activities, measured by homogenous fluorometric assays using synthetic donor particle substrates, were related to the incidence of a first CVD event in Framingham Heart Study Offspring participants without CVD (n = 2679, mean age 59 y, 56% women) attending the 6th examination cycle (1995-98). Because of an effect modification by sex for both CETP and PLTP, analyzes were stratified by sex.
  
  
  RESULTS
  During follow-up (mean 10.4 years) 187 participants experienced a first CVD event. In sex-specific Cox models, both CETP and PLTP as continuous and as binary variables were associated with significantly increased CVD in men, but not women. In men compared to a referent group with CETP ≥ median and PLTP < median, the multivariable-adjusted hazard ratio (HR) for new CVD events was significantly greater with either the combination of high CETP and high PLTP (HR 2.27, 95% CI 1.23-4.20); low CETP and low PLTP (HR 2.23, 95% CI 1.19-4.17); or low CETP and high PLTP (HR 2.85, 95% CI 1.53-5.31). In contrast, in women the multivariable-adjusted HR for new CVD events was non-significant and virtually equal to "1.0" with all combinations of high and low CETP or PLTP values.
  
  
  CONCLUSIONS
  Lower plasma CETP or higher PLTP activity was each associated with a significantly increased risk of CVD. Inexplicably, the increase in CVD associated with both lipid transfer proteins was confined to men.
authors.affiliation: Framingham Heart Study and Boston University School of Medicine, Boston, MA 01702-5803, USA. sjrobins@bu.edu
authors.forename: Sander J
authors.initials: SJ
authors.lastname: Robins
authors.forename: Asya
authors.initials: A
authors.lastname: Lyass
authors.forename: Robert W
authors.initials: RW
authors.lastname: Brocia
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000097:blood*; D010743:Phospholipids / Q000378:metabolism; D016016:Proportional Hazards Models; D012307:Risk Factors; D017678:Sex Distribution
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D002097:C-Reactive Protein