title: Role of senescence marker p16 INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults.
abstract: Adults older than 65 years undergo more than 120,000 coronary artery bypass (CAB) procedures each year in the United States. Chronological age alone, though commonly used in prediction models of outcomes after CAB, does not alone reflect variability in aging process; thus, the risk of complications in older adults. We performed a prospective study to evaluate a relationship between senescence marker p16(INK4a) expression in peripheral blood T-lymphocytes (p16 levels in PBTLs) with aging and with perioperative outcomes in older CAB patients. We included 55 patients age 55 and older, who underwent CAB in Johns Hopkins Hospital between September 1st, 2010 and March 25th, 2013. Demographic, clinical and laboratory data following outline of the Society of Thoracic Surgeons data collection form was collected, and p16 mRNA levels in PBTLs were measured using TaqMan® qRT-PCR. Associations between p16 mRNA levels in PBTLs with length of hospital stay, frailty status, p16 protein levels in the aortic and left internal mammary artery tissue, cerebral oxygen saturation, and augmentation index as a measure of vascular stiffness were measured using regression analyses. Length of hospital stay was the primary outcome of interest, and major organ morbidity, mortality, and discharge to a skilled nursing facility were secondary outcomes. In secondary analysis, we evaluated associations between p16 mRNA levels in PBTLs and interleukin-6 levels using regression analyses. Median age of enrolled patients was 63.5 years (range 56-81 years), they were predominantly male (74.55%), of Caucasian descent (85.45%). Median log2(p16 levels in PBTLs) were 4.71 (range 1.10-6.82). P16 levels in PBTLs were significantly associated with chronological age (mean difference 0.06 for each year increase in age, 95% CI 0.01-0.11) and interleukin 6 levels (mean difference 0.09 for each pg/ml increase in IL-6 levels, 95% CI 0.01-0.18). There were no significant associations with frailty status, augmentation index, cerebral oxygenation and p16 protein levels in blood vessels. Increasing p16 levels in PBTLs did not predict length of stay in the hospital (HR 1.10, 95% CI 0.87-1.40) or intensive care unit (HR 1.02, 95% CI 0.79-1.32). Additional evaluation of p16 levels in PBTLs as predictor of perioperative outcomes is required and should include additional markers of immune system aging as well as different outcomes after CAB in addition to length of hospital stay.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: apustav1@jhmi.edu.
authors.forename: Aliaksei
authors.initials: A
authors.lastname: Pustavoitau
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: vbarodk1@jhmi.edu.
authors.forename: Viachaslau
authors.initials: V
authors.lastname: Barodka
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: Norman_Sharpless@med.unc.edu.
authors.forename: Norman E
authors.initials: NE
authors.lastname: Sharpless
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: chad_torrice@med.unc.edu.
authors.forename: Chad
authors.initials: C
authors.lastname: Torrice
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: dnyhan@jhmi.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nyhan
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: dberkow1@jhmi.edu.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.affiliation: Department of Cardiac Surgery, Vanderbilt University, Nashville, TN, USA. Electronic address: ashah29@jhmi.edu.
authors.forename: Ashish S
authors.initials: AS
authors.lastname: Shah
authors.affiliation: Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: kbandeen@jhsph.edu.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Bandeen Roche
authors.affiliation: Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: jwalston@jhmi.edu.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015142:Baltimore; D016922:Cellular Senescence; D001026:Coronary Artery Bypass / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000097:blood* / Q000235:genetics; D005260:Female; D016330:Frail Elderly; D005819:Genetic Markers; D015577:Geriatric Assessment; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger
keywords: Aging biomarker; Chronological age; Coronary artery bypass; Frailty; Length of hospital stay; Peripheral blood T-lymphocytes; Senescence; p16(INK4a) levels