Background: High-density lipoprotein (HDL) cholesterol has been hypothesized to be a reliable marker of frailty and poor prognosis among the oldest elderly. Objective: In the present study, we evaluate the impact of HDL cholesterol on the risk of all-cause mortality in a large population of frail octogenarians and nonagenarians living in a community. Methods: We analyzed data from the Aging and Longevity Study in the Sirente geographic area (ilSIRENTE Study), a prospective cohort study that collected data on all subjects aged 80 year and older living in a mountain community (n = 359). The main outcome measure was the relative hazard ratio of death after 2 years of follow-up for different levels of HDL cholesterol. Results: A total of 86 deaths (30 men and 56 women) occurred during 2 years of follow-up. Among men the mean HDL cholesterol level was 36.7 ± 7.6 mg/dl among those who died as compared with 43.4 ± 10.3 mg/dl among survivors (p = 0.001). Similarly, among women, the mean HDL cholesterol level was 42.2 ± 11.5 mg/dl among those who died as compared with 49.3 ± 14.9 mg/dl among survivors (p = 0.001). Adjusting for potential confounders, including markers of frailty, LDL cholesterol, and triglycerides, somewhat reduced the strength of the association between HDL cholesterol levels and mortality, but it remained statistically significant. Conclusions: Our results obtained from a representative sample of very old and frail elderly subjects expand the knowledge that high levels of HDL cholesterol are associated with better survival. These findings support the hypothesis of a strong implication of the lipoprotein metabolism in the process of living an extremely long life.

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