No association was found between age and the percentage of participants with HDL-C >60 mg/dL. During the eight-year follow-up, there were a total of 1080 deaths from all causes, including 349 CVD deaths. Higher levels of HDL-C (>60 mg/dL) were significantly associated with a lower rate of CVD mortality after adjustment for age (Table 2). Non-CVD deaths were positively associated with higher levels of HDL-C after age adjustment (p = .0228). However, with adjustments for additional common risk factors (age, smoking, hypertension, alcohol intake, BMI, total cholesterol, diabetes, and physical activity index), the relative risk of non-CVD deaths was no longer associated with HDL-C levels (Table 3). The relative risk of CVD deaths remained strongly associated (p = .002) with HDL-C level after the same adjustments. Higher HDL-C levels were associated with healthy aging in participants older than 90 years (p = .047; Table 4).

Statistical methods used to calculate age group and the test of trends for age were calculated using the General Linear Model. The age-specific and age-adjusted rates of total mortality, CVD deaths, and other deaths for HDL-C levels and CETP variants were calculated in person-years. The differences between rates were tested using Cox's proportional hazard model, which was also used to estimate the relative risk for the linear effects of HDL-C on total and cause-specific mortalities after adjusting for age, smoking, hypertension, alcohol intake, BMI, cholesterol level, diabetes, and physical activity index. Age-adjusted mean levels of HDL and frequencies of the Int14A variant by healthy aging status were estimated using analysis of covariance. Fisher's exact test was used to compare proportions of healthy survivors across Int14A genotypes. Statistical software SAS (version 9; SAS Institute Inc., Cary, NC) was used in the statistical analysis.

Out of the 3448 men genotyped for CETP, 17 had the Int14A mutation. Although a trend suggested decreased all-cause mortality for men with the Int14A variant compared to those without the variant, the association failed to reach statistical significance (p = .20; Figure 1), possibly due to the small number of participants which provided only 13.9% power to detect a difference of this magnitude at the 5% level. However, of men who were considered healthy at baseline (free of six major chronic diseases and with high physical/cognitive function; n = 1495), those who possessed at least one copy of the Int14A variant (n = 9) were significantly more likely to remain healthy until at least 90 years of age (p = .025; Table 4). One hundred seventy-three men had the D442G missense mutation, but no association was found between this variant and mortality (p = .38).

BMI, alcohol consumption, smoking, physical activity index, fasting serum glucose, total cholesterol, and TG levels had significant negative associations with age (Table 1). Systolic BP levels increased significantly (p < .0001) with increasing age, but no trend was found relating age to hypertension. HDL-C levels increased significantly (p = .0034) with age. Of the 3562 participants analyzed for HDL-C, 22.7% had levels >60 mg/dL.

A strong inverse association exists between blood levels of HDL-C and theThe text is already properly formatted and free of spelling errors, duplicated letters, words or phrases. However, there are some minor grammatical errors that need to be corrected to improve readability and coherence. Here is the processed text with the suggested corrections:

CETP. However, it raises the important issue of assessing multiple age-related endpoints, including all-cause mortality. Disadvantages, as mentioned, include the small numbers of participants with one or more copies of the CETP gene variants of interest and limited statistical power. There is also the possibility that the protective effect for healthy aging is a false-positive finding. It should be replicated in other population samples. Another drawback if the finding is confirmed in other populations is that the mechanism may not necessarily be due to the blood level of CETP. Further work should attempt to correlate blood levels of CETP with healthy aging. Many such genetic findings may be population-specific. For example, the gene variants that we studied are prevalent in 2%-7% of the Japanese population (11) but are rare in other populations. Finally, another limitation of this study is that we are studying elderly individuals who have already survived, and survival factors may differ at younger ages. From http://biomedgerontology.oxfordjournals.org/ by guest on March 20, 2016.

Despite these hypothetical explanations for the contradictory findings, the reasons for such conflicting results are perplexing. It is possible that the focus on CETP inhibition leading to higher total plasma HDL levels and larger HDL particle size, the two most commonly touted protective mechanisms, may be overly simplistic. Recent work suggests that CETP inhibition does more than just raise HDL or alter HDL particle size. CETP also plays an important role as a modulator of HDL metabolism and affects its composition and properties (31). That is, CETP can alter the distribution and apolipoprotein make-up of HDL particles. Gene variants, such as I405V or Int 14A, which cause CETP deficiency, may cause the apoA-I in these particles to associate with apoA-II and other HDL apolipoproteins (except apoA-IV) forming HDL that differs in apolipoprotein composition and function.