Lipids and Lipoproteins Total plasma cholesterol, triglycerides, HDL, LDL, very LDL, and apolipoprotein A-I and B concentrations for Ashkenazi participants were performed by standard automated methods at the clinical laboratories of Montefiore Medical Center, Bronx, NY. The same lipid measurements were performed on fasting plasma samples from the Framingham Offspring Study as previously described. The LDL and HDL subclass levels and mean particle sizes were determined for all participants by nuclear magnetic resonance (NMR) spectroscopy at LipoScience Inc (Raleigh, NC) as previously described. Each NMR measurement produces the concentrations of 3 LDL subclasses and 5 HDL subclasses of varying size. From the LDL and HDL subclass levels are calculated weighted-mean LDL and HDL particle sizes (nm diameter) and LDL particle concentrations (nmol/L). Lipoprotein subclasses were grouped as large LDL (21.3-23.0 nm), intermediate LDL (19.8-21.2 nm), small LDL (18.3-19.7 nm), large HDL (8.8-13.0 nm), intermediate HDL (8.2-8.8 nm), and small HDL (7.3-8.2 nm). Although the LDL sizes ranged from 18.3 to 23.0 nm and HDL sizes from 7.3 to 13.0 nm, small changes within this range are associated with marked clinical differences in CVD risks.

In a case-control study, Ashkenazi Jews were recruited as described elsewhere. This population derived from an undetermined small number (estimated to be in the several thousands) of founders. External factors, including ecclesiastical edicts prohibiting all social contact with Jews, the Crusades, the establishment of the Pale of Settlement, numerous pogroms, and ethnic bigotry, resulted in the social isolation and inbreeding of the Ashkenazi Jews.

Statistical Analyses Because the extreme old age of the probands preempts a proper comparison (control) group, we also recruited the offspring of probands, some of whom presumably inherited longevity genes and thus should manifest the longevity phenotype. Candidate longevity phenotypes could then be compared between the offspring and age-matched Ashkenazi controls or non-Ashkenazi participants of the Framingham Offspring Study, neither of which are known to have longevity genes. There were no significant differences between the groups for routine blood chemistries, including electrolytes, liver function, and kidney function tests. Body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) was similar between offspring and the Ashkenazi control groups (P=.75 and P=.21 in women and men, respectively), both of which were significantly higher than in probands (TABLE 1). Typical measures of lipoproteins, including total cholesterol, HDL, LDL, and triglycerides were quite similar in probands compared with control group as well as between offspring and control groups. Only total cholesterol and LDL levels were lower in female probands vs control groups, and HDL levels were significantly higher in female offspring compared with Ashkenazi control groups. In contrast, there were marked differences between groups in lipoprotein particle sizes as determined by NMR. The HDL and LDL particle sizes in probands were markedly higher compared with both control groups (P=.001). Furthermore, the offspring of probands had a bimodal distribution of HDL particle sizes that was not seen in the control groups (P<.001), as well as a significantly different distribution of LDL particle size in offspring of probands compared with control groups. These distributions suggest that only a subset of offspring carry the high HDL trait, which may have been inherited in these individuals. Additionally, this distribution couldcorrection of spelling errors, word splitting, and grammar:

In the first sentence, "pro- bands" should be "probands." In the second sentence, "off- spring" should be "offspring." In the same sentence, "com- pared" should be "compared." In the third sentence, "til" should be "until." In the same sentence, "gests" should be "suggests." In the fourth sentence, "ticle" should be "particle."

In the fifth sentence, there is an unnecessary duplication of "the relationship." It should read: "The same relationship was apparent when men and women were considered separately."

In the sixth sentence, "considered" should be "controlling."

In Figure 1, the word "noitalupoP" is an error and should read "Population."

In Figure 2, there are several errors. The words "selcitraP" and "latoT" are errors and should read "Percentage" and "Total," respectively. The word "where" in the second-to-last sentence should be changed to "was."

In the last sentence, there is an unnecessary duplication of the word "lipoprotein." It should read: "...possible link between lipoprotein particle size and age-related..."Hypertension and cardiovascular disease (CVD) are risk factors for many causes of death. The metabolic syndrome, also known as insulin resistance syndrome or syndrome X, is also a risk factor for many age-related diseases, including CVD, dementia, infections, and cancer. This study analyzed cross-sectional data from probands with exceptional longevity aged 95 to 107 years (n=191), Ashkenazi and Framingham control groups combined aged 60 to 95 years (n=878), and their offspring aged 60 to 80 years (n=206). HDL indicates high-density lipoprotein; LDL, low-density lipoprotein.