A Prospective Study of High-Density Lipoprotein Cholesterol, Cholesteryl Ester Transfer Protein Gene Variants, and Healthy Aging in Very Old Japanese-American Men

作者：Koropatnick Tanya A; Kimbell Jennifer; Chen Randi; Grove John S; Donlon Timothy A; Masaki Kamal H; Rodriguez Beatriz L; Willcox Bradley J; Yano Katsuhiko; Curb J David^*

来源：Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 2008, 63(11): 1235-1240.

• High-density lipoprotein cholesterol (HDL-C)
• Cholesteryl ester transfer protein (CETP)
• Japanese Americans
• Cardiovascular disease
• Longevity
• Healthy aging

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 Lip 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.

• 出版日期2008-11