title: β2-microglobulin, cystatin C, and creatinine and risk of symptomatic peripheral artery disease.
abstract: BACKGROUND
  β2-Microglobulin and cystatin C may have advantages over creatinine in assessing risk associated with kidney function. We therefore investigated whether emerging filtration markers, β2-microglobulin and cystatin C, are prospectively associated with risk of the development of peripheral artery disease (PAD).
  
  
  RESULTS
  We conducted nested case-control studies among women within the Nurses' Health Study (1990-2010) and among men within the Health Professionals Follow-up Study (1994-2008) with the use of archived blood samples collected before PAD diagnosis. During follow-up, symptomatic PAD was confirmed in 144 women and 143 men. Controls were matched 3:1 based on age, race, smoking status, fasting status, and date of blood sampling. Conditional logistic regression models were used to estimate relative risks (RRs) and were adjusted for plasma creatinine and cardiovascular risk factors. In women, the RRs (95% CI) per 1-SD) increment were 1.16 (0.85 to 1.58) for β2-microglobulin and 0.94 (0.69 to 1.28) for cystatin C. Corresponding RRs in men were 1.50 (1.08 to 2.09) for β2-microglobulin and 1.54 (1.07 to 2.22) for cystatin C. There was no association between creatinine and PAD risk in women, whereas the association in men (RR 1.41, 95% CI 1.10 to 1.81) disappeared after adjustment for either β2-microglobulin or cystatin C. In pooled analyses of men and women, only β2-microglobulin was associated with PAD risk (RR 1.31, 95% CI 1.04 to 1.64).
  
  
  CONCLUSIONS
  In pooled analyses, β2-microglobulin was associated with an increased risk of symptomatic PAD; a similar association with cystatin C was observed only in men. The findings suggest that β2-microglobulin may capture the atherosclerosis-promoting or atherosclerosis-related elements of kidney dysfunction better than creatinine.
authors: Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (M.M.J., M.L.B., K.J.M.) Department of Nutrition, Harvard School of Public Health, Boston, MA (M.M.J., M.L.B., E.B.R.) Top Institute Food and Nutrition, Wageningen, The Netherlands (M.M.J., S.L.B.) University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, The Netherlands (M.M.J., R.T.G., S.L.B.).
authors: Michel M
authors: MM
authors: Joosten
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA (J.K.P., E.B.R.) Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA (J.K.P., J.P.C., E.B.R.).
authors: Jennifer K
authors: JK
authors: Pai
authors: Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (M.M.J., M.L.B., K.J.M.) Department of Nutrition, Harvard School of Public Health, Boston, MA (M.M.J., M.L.B., E.B.R.).
authors: Monica L
authors: ML
authors: Bertoia
authors: University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, The Netherlands (M.M.J., R.T.G., S.L.B.).
authors: Ron T
authors: RT
authors: Gansevoort
authors: Top Institute Food and Nutrition, Wageningen, The Netherlands (M.M.J., S.L.B.) University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, The Netherlands (M.M.J., R.T.G., S.L.B.).
authors: Stephan J L
authors: SJ
authors: Bakker
authors: Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA (J.K.P., J.P.C., E.B.R.) Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, TX (J.P.C.).
authors: John P
authors: JP
authors: Cooke
authors: Department of Nutrition, Harvard School of Public Health, Boston, MA (M.M.J., M.L.B., E.B.R.) Department of Epidemiology, Harvard School of Public Health, Boston, MA (J.K.P., E.B.R.) Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA (J.K.P., J.P.C., E.B.R.).
authors: Eric B
authors: EB
authors: Rimm
authors: Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (M.M.J., M.L.B., K.J.M.).
authors: Kenneth J
authors: KJ
authors: Mukamal
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D007383:Intermittent Claudication / Q000097:blood* / Q000453:epidemiology; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D001613:beta 2-Microglobulin; D003404:Creatinine
keywords: creatinine; cystatin C; kidney; peripheral artery disease; β2‐microglobulin