D’Agostino, Ralph B.

Fox, Caroline S.

Meigs, James B.

Pencina, Michael J.

Preis, Sarah Rosner

Vasan, Ramachandran S.

Diabetes Care

Meigs, James

Fox, Caroline

Harvard University - DASH

 Neck Circumference and the Development of CardiovascularDisease Risk Factors in the Framingham Heart Study  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Preis, Sarah Rosner, Michael J. Pencina, Ralph B. D’Agostino,James B. Meigs, Ramachandran S. Vasan, and Caroline S. Fox.2013. “Neck Circumference and the Development ofCardiovascular Disease Risk Factors in the Framingham HeartStudy.” Diabetes Care 36 (1): e3. doi:10.2337/dc12-0738.http://dx.doi.org/10.2337/dc12-0738.Published Version doi:10.2337/dc12-0738Accessed February 19, 2015 3:12:02 PM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879566Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAAOBSERVATIONSNeck Circumferenceand the Developmentof CardiovascularDisease Risk Factorsin the FraminghamHeart StudyUpper-body subcutaneous adiposetissue, estimated by neck circum-ference (NC), is a unique fat depotthat may confer additional risk for meta-bolic risk factors over generalized andcentral adiposity (1). Using a prospectivestudy design, we now evaluate whetherNC improves the prediction of incidentcardiovascular disease risk factors overBMI and waist circumference (2).Framingham Heart Study participants(n 5 2,732; 54% women; mean age, 57years) were followed for ;10 years (1995–2008)forthedevelopmentoftype2diabetes(fastingplasmaglucose$126mg/dLortreat-ment), hypertension, low HDL cholesterol(,40mg/dL,men;,50mg/dL,women),and high triglycerides ($150 mg/dLor lipid treatment). NC, BMI, and waistcircumference were standardized withineach sex to a mean of zero and an SD ofone. Logistic regression models, adjustedforage,sex,andsmoking,wereusedtotestthe association between 1 SD increment ofNC with each outcome. C-statistics werecalculated to assess the impact of addingNC to baseline models, and the net re-classiﬁcation improvement (NRI) statisticwas calculated to assess risk reclassiﬁcationimprovement (low, 0–1.9%; medium, 2.0–7.9%; high, $8% risk categories) (3,4).Inbaselinemodels,NCwasassociated(P,0.05)withalloutcomes.Afterfurtheradjustment for BMI and waist circumfer-ence, NC remained associated only withtype 2 diabetes (n 5 182, odds ratio [OR]5 1.57, 95% CI [1.24–1.98], P 50.0002). In this model, the OR for BMIwas 1.03 (95% CI [0.73–1.45], P 50.88), and the OR for waist circumferencewas 1.48(95% CI[1.05–2.10], P50.03).Additional adjustment for baseline fastingblood glucose resulted in an OR for NC of1.42 (95% CI [1.09–1.86], P 5 0.01).When NC was added to a modelcontaining an established type 2 diabetesrisk score (5), the OR for type 2 diabeteswas1.36(95%CI[1.12–1.66],P50.002),and the NRI was 10.2% (P , 0.0001).WhenNCwasaddedtoamodelcontainingthe individual clinical characteristics usedtoderivethetype2diabetesriskscore(age,sex, parental history of type 2 diabetes,BMI, hypertension, HDL cholesterol, andfastingplasmaglucose),theORwassimilar(OR1.53,95%CI[1.22–1.92],P50.0003).NC had a stronger effect on theincidence of type 2 diabetes in women(OR 5 2.77, 95% CI [2.18–3.53], P ,0.0001) compared with men (OR 51.76, 95% CI [1.43–2.15], P , 0.0001)(Pinteraction 5 0.006).For type 2 diabetes, the addition ofNC to a model containing baseline co-variates and BMI resulted in a change inthe C-statistic from 0.743 to 0.766 (P 50.004) and an NRI of 7.4% (P 5 0.01).When NC was added to a model with base-linelevelsoffastingplasmaglucoseandBMI,theC-statisticincreasedfrom0.885to0.891(P 5 0.01), and the NRI was 4.5%(P 5 0.03). Similar results were observedwhen waist circumference was substitutedfor BMI. When NC was added to a modelwith BMI and waist circumference, theC-statistic increased from 0.754 to 0.772 (P5 0.01), and the NRI was 4.9% (P 5 0.10).NC is associated with incident type 2diabetes and a clinically meaningful im-provement in the NRI. Our results arelimitedbythesinglefastingplasmaglucosemeasure and the exclusion of those whodid not return for follow-up. Whethermeasurement of NC improves type 2 di-abetes prediction over traditional adipositymeasures warrants further investigation.SARAH ROSNER PREIS, SCD, MPH1,2,3MICHAEL J. PENCINA, PHD3,4RALPH B. D’AGOSTINO,S R., PHD1,4JAMES B. MEIGS, MD, MPH5RAMACHANDRAN S. VASAN, MD1,6CAROLINE S. FOX, MD, MPH1,2,7From the1National Heart, Lung, and Blood In-stitute’s and Boston University’s FraminghamHeart Study, Framingham, Massachusetts; the2Center for Population Studies, National Heart,Lung, and Blood Institute, National Institutes ofHealth, Bethesda, Maryland; the3Department ofBiostatistics, Boston University School of PublicHealth, Boston, Massachusetts; the4Departmentof Mathematics and Statistics, Boston University,Boston, Massachusetts; the5General MedicineDivision, Massachusetts General Hospital andHarvard Medical School, Boston, Massachusetts;the6Sections of Preventive Medicine and Cardi-ology, Department of Medicine, Boston Univer-sity School of Medicine, Boston, Massachusetts;and the7Division of Endocrinology and Metab-olism, Brigham and Women’s Hospital and Har-vard Medical School, Boston, Massachusetts.Corresponding author: Sarah Rosner Preis, srpreis@bu.edu.DOI: 10.2337/dc12-0738© 2013 by the American Diabetes Association.Readers may use this article as long as the work isproperly cited, the use is educational and not forproﬁt, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ fordetails.Acknowledgments—This work was sup-ported by the National Heart, Lung, andBlood Institute’s Framingham Heart Study(N01-HC-25195). J.B.M. is supported in partby a National Institute of Diabetes and Di-gestive and Kidney Diseases (NIDDK) grant(K24 DK080140). R.S.V.issupportedinpartby an NIDDK/National Institutes of Healthgrant (RO1DK080739).No potential conﬂicts of interest relevant tothis article were reported.S.R.P. researched data and wrote the man-uscript. M.J.P. researched data and reviewedand edited the manuscript. R.B.D. and J.B.M.reviewed and edited the manuscript. R.S.V.reviewed and edited the manuscript andcontributed to discussion. C.S.F. researcheddata, reviewed and edited the manuscript,and contributed to discussion. S.R.P. andC.S.F. are the guarantors of this work and,as such, had full access to all the data in thestudy and take responsibility for the integrityof the data and the accuracy of the dataanalysis.ccccccccccccccccccccccccReferences1. Grunfeld C, Rimland D, Gibert CL, et al.Association of upper trunk and visceral ad-ipose tissue volume with insulin resistancein control and HIV-infected subjects inthe FRAM study. J Acquir ImmuneDeﬁc Syndr 2007;46:283–2902. Preis SR, Massaro JM, Hoffmann U, et al.Neck circumference as a novel measure ofcardiometabolic risk: the FraminghamHeart study. J Clin Endocrinol Metab2010;95:3701–37103. Pencina MJ, D’Agostino RB Sr, D’AgostinoRB Jr, Vasan RS. Evaluating the added pre-dictive ability of a new marker: from areaundertheROCcurvetoreclassiﬁcationandbeyond. Stat Med 2008;27:157–172; dis-cussion 207–2124. Meigs JB, Shrader P, Sullivan LM, et al.Genotype score in addition to commonrisk factors for prediction of type 2 dia-betes. N Engl J Med 2008;359:2208–22195. Wilson PW, Meigs JB, Sullivan L, Fox CS,Nathan DM, D’Agostino RB Sr. Predictionof incident diabetes mellitus in middle-aged adults: the Framingham OffspringStudy. Arch Intern Med 2007;167:1068–1074care.diabetesjournals.org DIABETES CARE, VOLUME 36, JANUARY 2013 e3ONLINE LETTERS

Neck Circumference and the Development of Cardiovascular Disease Risk Factors in the Framingham Heart Study

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Neck Circumference and the Development of Cardiovascular Disease Risk Factors in the Framingham Heart Study

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