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Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults.

Publication ,  Journal Article
Kraus, VB; Ma, S; Tourani, R; Fillenbaum, GG; Burchett, BM; Parker, DC; Kraus, WE; Connelly, MA; Otvos, JD; Cohen, HJ; Orenduff, MC; Zhang, X ...
Published in: Ebiomedicine
November 2022

BACKGROUND: The hard endpoint of death is one of the most significant outcomes in both clinical practice and research settings. Our goal was to discover direct causes of longevity from medically accessible data. METHODS: Using a framework that combines local causal discovery algorithms with discovery of maximally predictive and compact feature sets (the "Markov boundaries" of the response) and equivalence classes, we examined 186 variables and their relationships with survival over 27 years in 1507 participants, aged ≥71 years, of the longitudinal, community-based D-EPESE study. FINDINGS: As few as 8-15 variables predicted longevity at 2-, 5- and 10-years with predictive performance (area under receiver operator characteristic curve) of 0·76 (95% CIs 0·69, 0·83), 0·76 (0·72, 0·81) and 0·66 (0·61, 0·71), respectively. Numbers of small high-density lipoprotein particles, younger age, and fewer pack years of cigarette smoking were the strongest determinants of longevity at 2-, 5- and 10-years, respectively. Physical function was a prominent predictor of longevity at all time horizons. Age and cognitive function contributed to predictions at 5 and 10 years. Age was not among the local 2-year prediction variables (although significant in univariable analysis), thus establishing that age is not a direct cause of 2-year longevity in the context of measured factors in our data that determine longevity. INTERPRETATION: The discoveries in this study proceed from causal data science analyses of deep clinical and molecular phenotyping data in a community-based cohort of older adults with known lifespan. FUNDING: NIH/NIA R01AG054840, R01AG12765, and P30-AG028716, NIH/NIA Contract N01-AG-12102 and NCRR 1UL1TR002494-01.

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Published In

Ebiomedicine

DOI

EISSN

2352-3964

Publication Date

November 2022

Volume

85

Start / End Page

104292

Location

Netherlands

Related Subject Headings

  • Longevity
  • Humans
  • Exercise
  • Cohort Studies
  • Aged
  • 1117 Public Health and Health Services
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Kraus, V. B., Ma, S., Tourani, R., Fillenbaum, G. G., Burchett, B. M., Parker, D. C., … Aliferis, C. F. (2022). Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults. Ebiomedicine, 85, 104292. https://doi.org/10.1016/j.ebiom.2022.104292
Kraus, Virginia Byers, Sisi Ma, Roshan Tourani, Gerda G. Fillenbaum, Bruce M. Burchett, Daniel C. Parker, William E. Kraus, et al. “Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults.Ebiomedicine 85 (November 2022): 104292. https://doi.org/10.1016/j.ebiom.2022.104292.
Kraus VB, Ma S, Tourani R, Fillenbaum GG, Burchett BM, Parker DC, et al. Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults. Ebiomedicine. 2022 Nov;85:104292.
Kraus, Virginia Byers, et al. “Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults.Ebiomedicine, vol. 85, Nov. 2022, p. 104292. Pubmed, doi:10.1016/j.ebiom.2022.104292.
Kraus VB, Ma S, Tourani R, Fillenbaum GG, Burchett BM, Parker DC, Kraus WE, Connelly MA, Otvos JD, Cohen HJ, Orenduff MC, Pieper CF, Zhang X, Aliferis CF. Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults. Ebiomedicine. 2022 Nov;85:104292.
Journal cover image

Published In

Ebiomedicine

DOI

EISSN

2352-3964

Publication Date

November 2022

Volume

85

Start / End Page

104292

Location

Netherlands

Related Subject Headings

  • Longevity
  • Humans
  • Exercise
  • Cohort Studies
  • Aged
  • 1117 Public Health and Health Services
  • 1103 Clinical Sciences