title: Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study.
abstract: Cardiovascular disease and frailty frequently occur together. Both are associated with inflammation, which may be partially triggered by oxidative stress, especially in cardiovascular disease. We investigated whether inflammatory and oxidative stress biomarkers linked to cardiovascular disease were associated with frailty and the related outcome of gait speed. We report cross-sectional associations of biomarkers and frailty assessed at Framingham Offspring Study cycle eight. Participants ≥60 years were eligible if they had information on frailty and at least one of the following: C-reactive protein, interleukin-6, tumor necrosis factor receptor 2, 8-epi-FGFα isoprostanes (isoprostanes), lipoprotein phospholipase A2 (LpPLA2) mass or activity, osteoprotegerin, intracellular adhesion molecule-1, monocyte chemoattractant protein-1 or P-selectin. Stepwise logistic models were utilized for frailty and stepwise linear models for gait speed. Covariates included age, sex, body mass index, smoking, and co-morbidities. Odds ratios (ORs) and slope estimates (B) are reported per standard deviation increase of loge-transformed biomarker. Of the 1919 participants, 142 (7 %) were frail. In a stepwise model, frailty odds increased with higher interleukin-6 (OR 1.90, 95 % CI 1.51, 2.38), isoprostanes (OR 1.46, 95 % CI 1.12, 1.92), and LpPLA2 mass (OR 1.29, 95 % CI 1.00, 1.65). Stepwise regression found that slower gait speeds were associated with interleukin-6 (B = -0.025 m/s, 95 % CI 0.04, -0.01), isoprostanes (B = -0.019, 95 % CI -0.03, -0.008), LpPLA2 mass (B = -0.016, 95 % CI -0.03, -0.004), and osteoprotegerin (B = -0.015, 95 % CI -0.03, -0.002, all p < 0.05). Interleukin-6, isoprostanes, and LpPLA2 mass were associated with greater frailty odds and slower gait speeds. Oxidative stress may be a mechanism contributing to frailty.
authors.affiliation: Section of Geriatrics, Department of Medicine, Boston University School of Medicine, 88 E Newton Street, Robinson 2, Boston, MA, 02118, USA. Christine.Liu@bmc.org.|Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Christine.Liu@bmc.org.
authors.forename: Christine K
authors.initials: CK
authors.lastname: Liu
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA, 01702, USA.|Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
authors.forename: Asya
authors.initials: A
authors.lastname: Lyass
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA, 01702, USA.|Department of Mathematics and Statistics, Boston University, Boston, MA, USA.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA, 01702, USA.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA, 01702, USA.|Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA, 01702, USA.|Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.|Sections of Cardiovascular and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: National Heart, Lung and Blood Institute's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA, 01702, USA. murabito@bu.edu.|Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. murabito@bu.edu.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016330:Frail Elderly; D006801:Humans; D015994:Incidence; D008297:Male; D009391:Nephelometry and Turbidimetry; D016017:Odds Ratio; D018384:Oxidative Stress / Q000502:physiology*; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers
keywords: Frailty; Gait speed; Inflammation; Oxidative stress