Beiser, Alexa

D’Agostino, Ralph B.

Fox, Caroline S.

Massaro, Joseph M.

O’Connor, George T.

O’Donnell, Christopher J.

Pencina, Karol M.

Polak, Joseph F.

Rosenquist, Klara J.

Seshadri, Sudha

Wolf, Philip A.

Diabetes Care

Harvard University - DASH 

 Neck Circumference, Carotid Wall Intima-Media Thickness, andIncident Stroke  (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 Rosenquist, K. J., J. M. Massaro, K. M. Pencina, R. B.D’Agostino, A. Beiser, G. T. O’Connor, C. J. O’Donnell, et al.2013. “Neck Circumference, Carotid Wall Intima-MediaThickness, and Incident Stroke.” Diabetes Care 36 (9): e153-e154. doi:10.2337/dc13-0379. http://dx.doi.org/10.2337/dc13-0379.Published Version doi:10.2337/dc13-0379Accessed February 16, 2015 10:47:05 PM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:12987296Terms 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 Circumference,Carotid WallIntima-MediaThickness, andIncident StrokeLocally acting fat depots may contrib-ute to obesity complications, inparticular vascular disease, throughdirect paracrine effects (1,2). The carotidarteries are encased in fat, and total upper-bodysubcutaneousfatisestimatedbyneckcircumference (NC). NC has been inde-pendentlycorrelatedwithcardiometabolicriskfactorsaboveandbeyondthatofotheradiposity measures (3,4). Carotid wallintima-media thickness (IMT) is a surro-gate marker of subclinical atherosclerosisand has been associated with cardiovascu-lar and stroke outcomes (5). The aim ofthis study was to evaluate the associationof NC and carotid wall IMT above andbeyond traditional cardiovascular risk fac-tors and generalized adiposity.Framingham Heart Study offspringparticipants who underwent carotid ultra-sonography and NC measurements wereincluded (n 5 3,274; mean age 59 years;52% women); NC, internal carotid artery(ICA) IMT, and common carotid artery(CCA) IMT were determined as previouslydescribed (4,5). Linear regression modelsevaluated the association between adipos-ityexposuresandIMT.NC,BMI,andwaistcircumferencewerestandardizedtoameanof 0 and SD of 1 to make the b-coefﬁcientscomparable per 1-SD increase of each in-dependent variable. We secondarily ad-justed for sleep-disordered breathingfrom a self-assessment questionnaire. Coxproportional hazards models were used toassess thelongitudinalassociation betweenadiposity measures and incident stroke.NC, BMI, and waist were correlatedwith IMT (Table 1). In multivariablemodels, a 1-SD increase in NC was associ-atedwitha0.071-mm increaseinICAIMT(P 5 0.001), which remained signiﬁcantafter BMI adjustment (P , 0.0001). Nei-ther BMI (P 5 0.64) nor waist (P 5 0.38)was associated with ICA IMT. The associa-tion between NC and ICA was similar andremained signiﬁcant after adjustment forsleep. Per 1-SD increase in NC, the CCAwas 0.025 mm higher (P , 0.001), whichremained signiﬁcant after BMI adjustment(P , 0.001). Signiﬁcant but smaller asso-ciations were observed for BMI and waist,whichwereattenuateduponadditionalad-justment for NC. The association betweenNC and CCA was slightly attenuated (b 50.017,P50.003)butremainedsigniﬁcantafter adjustment for sleep.NC, BMI, and waist were not associ-ated with incidentstrokeover 6.1years offollow-up (n 5 147 events); subgroupanalysis excluding transient ischemic at-tacks and evaluating the outcomes bystroke type showed results similar to theprimary analysis (data not shown).NC, but neither BMI nor waist, wasassociated with ICA IMT. CCA IMT is pre-ferentially associated with NC after adjust-ment for BMI and waist. Finally, NC, BMI,andwaistwerenotassociatedwithincidentstroke. Strengths include a well-deﬁnedcohort with comprehensive clinical charac-terization.Somelimitationswarrantmention.Evaluation of sleep-disordered breathingwas based on available data; more robustmeasures are needed to evaluate this associ-ation.Thesmallnumberofstrokeeventsandrelatively short follow-up time may havelimited our power. The correlation betweenNCandvolumetricevaluationofupper-bodysubcutaneous fat has yet to be determined.This study was hypothesis generating andnot intended to impact clinical practice. NCis uniquely associated with carotid IMT.Upper-bodysubcutaneousfatmayhaveadi-rect pathogenic impact on local vasculature.KLARA J. ROSENQUIST, MD1,2,3JOSEPH M. MASSARO, PHD2,4KAROL M. PENCINA, PHD5RALPH B. D’AGOSTINO, PHD2,5ALEXA BEISER, PHD2,4,7GEORGE T. O’CONNOR, MD, MS2,6CHRISTOPHER J. O’DONNELL, MD, MPH2,3PHILIP A. WOLF, MD2,7JOSEPH F. POLAK, MD, MPH8SUDHA SESHADRI, MD2,7CAROLINE S. FOX, MD, MPH1,2,3Table 1—Comparison of outcomes based on NC, BMI, and waist circumference among 3,274 participants of theFramingham Heart Study offspring cohortNC (cm) BMI (kg/m2) Waist circumference (cm)Correlationcoefﬁcient or b PCorrelationcoefﬁcient or b PCorrelationcoefﬁcient or b PICA IMTAge- and sex-adjusted Pearson correlation coefﬁcient 0.12 ,0.001 0.06 ,0.001 0.07 ,0.001Multivariable-adjusted linear regression bper 1-SD increase in adiposity measure (SE)a 0.071 (0.022) 0.001 0.007 (0.015) 0.64 0.013 (0.015) 0.38CCA IMTAge- and sex-adjusted Pearson correlation coefﬁcient 0.19 ,0.001 0.14 ,0.001 0.14 ,0.001Multivariable-adjusted linear regression bper 1-SD increase in adiposity measure (SE)a 0.025 (0.003) ,0.0001 0.011 (0.002) ,0.0001 0.011 (0.002) ,0.0001Incident stroke (n 5 147)Age- and sex-adjusted HR per 1-SD increase inadiposity measure (95% CI) 1.25 (0.99–1.58) 0.06 1.08 (0.91–1.27) 0.40 1.13 (0.95–1.34) 0.18Multivariate-adjusted Cox proportional HR per 1-SDincrease in adiposity measure (95% CI)b 0.99 (0.77–1.27) 0.94 0.94 (0.79–1.13) 0.52 0.98 (0.82–1.18) 0.84HR, hazard ratio.aMultivariable linear regression model adjusted for age, sex, systolic blood pressure, hypertension treatment, diabetes, total cholesterol–to–HDLcholesterol ratio, and smoking.bCox proportional HR adjusted for age, sex, systolic blood pressure, hypertension treatment, diabetes, total cholesterol–to–HDLcholesterol ratio, smoking, prevalent cardiovascular disease, and prevalent atrial ﬁbrillation.care.diabetesjournals.org DIABETES CARE, VOLUME 36, SEPTEMBER 2013 e153ONLINE LETTERSFrom the1Division of Endocrinology and Metabo-lism, Brigham and Women’s Hospital and Har-vard Medical School, Boston, Massachusetts;the2National Heart, Lung, and Blood Institute’sFramingham Heart Study, Framingham, Massa-chusetts; the3National Heart, Lung, and BloodInstitute Division of Intra-mural Research andthe Center for Population Studies, Framingham,Massachusetts; the4Department of Biostatistics,BostonUniversity School of Public Health, Boston,Massachusetts; the5Department of Mathematicsand Statistics, Boston University, Boston, Massa-chusetts; the6Department of Medicine, BostonUniversity School of Medicine, Boston, Massa-chusetts; the7Department of Neurology, BostonUniversity School of Medicine, Boston, Massa-chusetts; and the8Department of Radiology, TuftsMedical Center, Boston, Massachusetts.Corresponding author: Caroline S. Fox, foxca@nhlbi.nih.gov.DOI: 10.2337/dc13-0379© 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 research was con-ducted in part using data and resources fromthe Framingham Heart Study of the NationalHeart, Lung, and Blood Institute (NHLBI) ofthe National Institutes of Health and BostonUniversity School of Medicine. This work wassupported by the NHLBI’s Framingham HeartStudy (contract no. N01-HC-25195) and theNational Institute of Neurological Disordersand Stroke (R01 NS17950). K.J.R. is sup-ported through funding from the WhitakerCardiovascular Institute (T32 HL007224).J.F.P. is supported by grants from the NHLBI(R01 HL069003 and HL081352). A.B.,P.A.W., and S.S. are also supported by grantsfrom the National Institute on Aging (R01033193, 031287, 08122, and 33040).No potential conﬂicts of interest relevant tothis article were reported.K.J.R. designed the study. J.M.M. andK.M.P. completed the statistical analyses andreviewed and edited the manuscript. R.B.D.,A.B., G.T.O., C.J.O., and P.A.W. contributedto the discussion and reviewed and edited themanuscript. J.F.P. and S.S. provided the re-searchdata,contributedto thediscussion,andreviewed and edited the manuscript. K.J.R.and C.S.F. designed the study, led the statis-ticalanalysis,andwrotethemanuscript.K.J.R.andC.S.F.are theguarantorsofthisworkand,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.Partsofthisstudywerepresentedinabstractform at the American Heart Association Epi-demiology and Prevention/Nutrition, PhysicalActivity and Metabolism 2013 ScientiﬁcS e s -sions, New Orleans, Louisiana, 19–22 March2013.ccccccccccccccccccccccccReferences1. Eringa EC, Bakker W, van Hinsbergh VW.Paracrine regulation of vascular tone, in-ﬂammation and insulin sensitivity by peri-vascular adipose tissue. Vascul Pharmacol2012;56:204–2092. Fox CS, Massaro JM, Schlett CL, et al. Peri-aortic fat deposition is associated with pe-ripheral arterial disease: the FraminghamHeart Study. Circ Cardiovasc Imaging2010;3:515–5193. Fitch KV, Stanley TL, Looby SE, Rope AM,Grinspoon SK. Relationship between neckcircumference and cardiometabolic param-etersinHIV-infectedandnon-HIV-infectedadults. Diabetes Care 2011;34:1026–10314. Preis SR, Massaro JM, Hoffmann U, et al.Neck circumference as a novel measure ofcardiometabolic risk: the FraminghamHeart Study. J Clin Endocrinol Metab2010;95:3701–37105. PolakJF,PencinaMJ,PencinaKM,O’DonnellCJ, Wolf PA, D’Agostino RB Sr. Carotid-wall intima-media thickness and cardio-vascular events. N Engl J Med 2011;365:213–221e154 DIABETES CARE, VOLUME 36, SEPTEMBER 2013 care.diabetesjournals.orgOnline Letters

Neck Circumference, Carotid Wall Intima-Media Thickness, and Incident Stroke

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Neck Circumference, Carotid Wall Intima-Media Thickness, and Incident Stroke

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