title: Validation of Biomarkers of CVD Risk from Dried Blood Spots in Community-Based Research: Methodologies and Study-Specific Serum Equivalencies.
abstract: Dried blood spot (DBS) methodology offers significant advantages over venipuncture in studies of vulnerable populations or large-scale studies, including reduced participant burden and higher response rates. Uncertainty about the validity of cardiovascular disease (CVD) risk biomarkers remains a barrier to wide-scale use. We determined the validity of DBS-derived biomarkers of CVD risk versus gold-standard assessments, and study-specific, serum-equivalency values for clinical relevance of DBS-derived values. Concurrent venipuncture serum and DBS samples (n = 150 adults) were assayed in Clinical Laboratory Improvement Amendments-certified and DBS laboratories, respectively. Time controls of DBS standard samples were assayed single-blind along with test samples. Linear regression analyses evaluated DBS-to-serum equivalency values; agreement and bias were assessed via Bland-Altman plots. Linear regressions of venipuncture values on DBS-to-serum equivalencies provided R(2) values for total cholesterol, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein (CRP) of 0.484, 0.118, and 0.666, respectively. Bland-Altman plots revealed minimal systematic bias between DBS-to-serum and venipuncture values; precision worsened at higher mean values of CRP. Time controls revealed little degradation or change in analyte values for HDL-C and CRP over 30 weeks. We concluded that DBS-assessed biomarkers represent a valid alternative to venipuncture assessments. Large studies using DBS should include study-specific serum-equivalency determinations to optimize individual-level sensitivity, the viability of detecting intervention effects, and generalizability in community-level primary prevention interventions.
authors.affiliation: a Department of Psychology , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Samuelsson
authors.affiliation: b Department of Psychiatry , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA.
authors.forename: Martica H
authors.initials: MH
authors.lastname: Hall
authors.affiliation: c Warren Alpert Medical School , Brown University , Providence , RI , USA.
authors.forename: Shakir
authors.initials: S
authors.lastname: McLean
authors.affiliation: d Department of Medicine , Brigham and Women's Hospital, Boston, MA, USA, Center for Population and Development Studies, Harvard School of Public Health , Cambridge , MA , USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Porter
authors.affiliation: e Department of Epidemiology , Harvard Center for Population and Development Studies, Cambridge, MA, USA, Harvard School of Public Health , Boston , MA , USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Berkman
authors.affiliation: f Department of Family Medicine , Oregon Health and Science University , Portland , OR , USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marino
authors.affiliation: g CUNY School of Public Health, Hunter College , New York , NY , USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Sembajwe
authors.affiliation: h Department of Anthropology and Institute for Policy Research , Northwestern University , Evanston , IL , USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McDade
authors.affiliation: i Division of Sleep Medicine , Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, Department of Social and Behavioral Sciences, Harvard School of Public Health, Cambridge, MA, USA, Department of Biobehavioral Health, Pennsylvania State University , State College , PA , USA.
authors.forename: Orfeu M
authors.initials: OM
authors.lastname: Buxton
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D059788:Dried Blood Spot Testing / Q000592:standards* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011786:Quality Control; D012044:Regression Analysis; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D002097:C-Reactive Protein; D002784:Cholesterol