A prospective study of high-density lipoprotein cholesterol, cholesteryl ester transfer protein gene variants, and healthy aging in very old Japanese-american men.
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.
Koropatnick
Tanya A
TA
Pacific Health Research Institute, 846 South Hotel St., Suite 301, Honolulu, Hawaii 96813, USA.
Kimbell
Jennifer
J
Chen
Randi
R
Grove
John S
JS
Donlon
Timothy A
TA
Masaki
Kamal H
KH
Rodriguez
Beatriz L
BL
Willcox
Bradley J
BJ
Yano
Katsuhiko
K
Curb
J David
JD
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
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL