title: A prospective study of high-density lipoprotein cholesterol, cholesteryl ester transfer protein gene variants, and healthy aging in very old Japanese-american men.
abstract: BACKGROUND
  High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP).
  
  
  METHODS
  Japanese-American men (n = 3562) were followed for up to 8 years, from average age 78 to average age 84 (maximum age 99), or until death. Total mortality, cause-specific mortality, and healthy survival were evaluated for associations with HDL-C level and CETP genetic variants common in the Japanese population (CD442G and Int 14A).
  
  
  RESULTS
  HDL-C was negatively associated with cardiovascular disease (CVD) mortality (p =.002) but not related to non-CVD (p =.147) or total (p =.547) mortality after adjustment for common risk factors. There was a trend for lower mortality for the men with the Int 14A variant. These men also had higher HDL-C levels (p =.047) and were significantly more likely to be healthy survivors (absence of six major age-related diseases and high physical/cognitive function) beyond the age of 90 years (p =.005).
  
  
  CONCLUSIONS
  Low HDL-C level is a risk factor for CVD mortality in elderly Japanese-American men. High HDL-C and the Int 14A variant of the CETP gene may increase odds for healthy aging.
authors.affiliation: Pacific Health Research Institute, 846 South Hotel St., Suite 301, Honolulu, Hawaii 96813, USA.
authors.forename: Tanya A
authors.initials: TA
authors.lastname: Koropatnick
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kimbell
authors.forename: Randi
authors.initials: R
authors.lastname: Chen
authors.forename: John S
authors.initials: JS
authors.lastname: Grove
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Donlon
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Masaki
authors.forename: Beatriz L
authors.initials: BL
authors.lastname: Rodriguez
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Willcox
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yano
authors.forename: J David
authors.initials: JD
authors.lastname: Curb
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000401:mortality; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D006254:Hawaii; D006801:Humans; D007564:Japan / Q000208:ethnology; D008075:Lipoproteins, HDL / Q000097:blood*; D008136:Longevity / Q000502:physiology*; D008297:Male
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL