Low High‐Density Lipoprotein 3 Reduces the Odds of Men Surviving to Age 85 During 53‐Year Follow‐Up

Abstract

Objectives To identify high-density lipoprotein (HDL) subfractions associated with longevity in men. Design Fifty-three-year prospective follow-up of Gofman’s Livermore Cohort between 1954 and 2008. Setting Lawrence Livermore National Laboratory. Participants One thousand one hundred forty-four men who consented to the study, had analytic ultracentrifuge measurements of lipoprotein subfractions at baseline, and were old enough at baseline to have survived to age 85 during follow-up. Measurements Survival was determined according to participant contact, Social Security Death Index, and National Death Index. Results Three hundred ninety men survived to 85 years old (34.1%). Survivors were less likely than nonsurvivors to be in the lowest HDL3 (% (standard error) 18.5% (2.0%) vs 27.3% (1.6%), P < .001) and HDL2 (22.1% (2.1%) vs 27.7% (1.6%), P = 0.04) quartiles. Logistic regression analyses showed that the lowest HDL3 quartile significantly predicted shorter longevity (P = 0.002), whereas the linear increases per mg/dL of HDL3 did not (P = 0.38), suggesting a risk threshold proximal to the 25th percentile. Men who were above the 25th HDL3 percentile had 70% greater odds of surviving until age 85 than those below this level, which persisted when adjusted for HDL2, very low-density lipoprotein (LDL), and standard risk factors. Proportional hazard analyses of survival before age 85 showed that being in the lowest HDL3 quartile increased age-adjusted cancer risk by 39% (P = 0.05) and noncancer risk by 23% (P = 0.04) when adjusted for other risk factors. Survivors also smoked less (mean ± SD 0.31 ± 0.48 vs 0.57 ± 0.56 packs/d, P < .001), had lower systolic (118.36 ± 11.08 vs 122.81 ± 13.55 mmHg, P < .001) and diastolic (70.61 ± 8.59 vs 73.14 ± 9.22 mmHg, P < .001) blood pressures and lower LDL mass (359.55 ± 80.42 vs 374.37 ± 86.10 mg/dL, P = 0.009) and total cholesterol concentrations (229.51 ± 43.21 vs 235.89 ± 45.40 mg/dL, P = 0.04) than nonsurvivors. Conclusion Low HDL3 reduces the odds of extended survival in men, independent of HDL2, other lipoproteins, and standard risk factors.

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

“…There are technical challenges related to different methods of HDL subfractioning (Superko et al, 2012). Still, our results agree with the general notion that the favorable effects observed for HDL are predominantly exerted by the smaller and denser HDL particles (Yu et al, 2003;Williams, 2012;Martin et al, 2014).…”

High-density lipoprotein subfractions and carotid plaque: The Northern Manhattan Study

“…In addition, HDL3-C has been more effective than HDL2-C in inhibiting vascular cell adhesion molecule expression in endothelial cells 29 , involved in mediating the process of early atherosclerosis. The benefits of HDL3-C have also been recently extended to increased longevity 30 , as well as reduced risk of cancer in men 31 . Also, smaller and more dense HDL3-C subfraction represents the major subfraction in newborns, thus providing a greater protection against infection in early life 32 .…”

High-density lipoprotein and endothelial function in patients with myocardial infarction: Pieces in a puzzle

“…Similar results were also reached in diverse primary prevention populations inclusive of Caucasian and African-American men and women from the Framingham Offspring Cohort and Jackson Heart Studies, where evidence supports HDL 3 -C as the primary link to coronary risk and mortality [14, 15]. The longest available follow-up (53 years) comes from Gofman's Livermore Cohort wherein analytic ultracentrifugation was performed at baseline to measure HDL subclass mass [15].…”

“…The longest available follow-up (53 years) comes from Gofman's Livermore Cohort wherein analytic ultracentrifugation was performed at baseline to measure HDL subclass mass [15]. In an analysis of 1144 men, 34% survived to age 85, and the odds of survival were 70% higher for men above the lowest quartile of HDL 3 -C compared to men within that lowest HDL 3 -C group, a finding that persisted after adjustment for standard risk factors.…”