Ntu 1: Lub raum Ua Haujlwm Thiab Lipid Metabolism Yog Cov Kev Ua Phem Loj Ntawm Circumpapillary Retinal Nerve Fiber Layer Thickness—Lub Neej-Kev Kawm Rau Cov Neeg Laus

Yog xav paub ntxiv:tina.xiang@wecistanche.com

Abstract

Keeb kwm: circumpapillary retinal paj fiber txheej thickness (cpRNFLT) raws li kev soj ntsuam los ntawm spectral-domain optical coherence tomography (SD-OCT) yog ib tug tshiab txheej txheem siv rau kev tshawb nrhiav thiab kev ntsuam xyuas ntawm glaucoma thiab lwm yam optic neuropathies. Ua ntej txhais cpRNFLT mus rau hauv tsev kho mob, nws yog ib qho tseem ceeb heev uas yuav tau soj ntsuam anthropometric, biochemical, thiab soj ntsuam tsis muaj feem cuam tshuam rau cpRNFLT nyob rau hauv ib tug loj cov ntaub ntawv raws li cov pejxeem.

Cov txheej txheem: Cov pej xeem raws li LIFE-Adult Study Random xaiv 10, 000 cov neeg koom los ntawm cov pej xeem sau npe ntawm Leipzig, Lub teb chaws Yelemees. Txhua tus neeg tuaj koom tau txais cov qauv kev ntsuas kev ntsuas ntawm ntau yam kev pheej hmoo cardiometabolic thiab cov duab ntawm lub qhov muag, suav nrog kev ntsuas cpRNFLT siv SD-OCT (Spectralis, Heidelberg Engineering). Tom qab ua haujlwm nruj SD-OCT cov qauv zoo, 8952 tus neeg raug tshuaj xyuas. Multivariable linear regression analyses tau siv los soj ntsuam cov koom haum ywj pheej ntawm ntau yam kev pheej hmoo cardiometabolic cov cim nrog cov haujlwm tshwj xeeb cpRNFLT Rau cov cim tseem ceeb, cov txheeb ze lub zog ntawm cov koom haum soj ntsuam raws li muab piv rau ib leeg los txheeb xyuas cov yam tseem ceeb tshaj plaws cuam tshuam rau cpRNFLT. Hauv txhua qhov kev tshuaj ntsuam, qhov kev tshawb pom tsis tseeb tus qauv rau ntau qhov kev sib piv tau siv.

Cov txiaj ntsig: Nyob rau hauv tag nrho pawg, cov poj niam cov kev kawm tau thicker thoob ntiaj teb thiab tseem sectoral cpRNFLT piv rau txiv neej cov ntsiab lus (p < 0.05).="" multivariable="" linear="" regression="" analyzes="" qhia="" ib="" qho="" tseem="" ceeb="" thiab="" ywj="" siab="" koom="" haum="" ntawm="" lub="" ntiaj="" teb="" no="" thiab="" sectoral="" cprnflt="" nrog="" biomarkers="">lub raum ua haujlwmthiablipid profile. Yog li, thinner cpRNFLT tau cuam tshuam nrog qhov phem dualub raum ua haujlwmRaws li kev soj ntsuam los ntawm cystatin C thiab kwv yees glomerular pom tus nqi. Tsis tas li ntawd, ib qho tsis zoo li lipid profile (piv txwv li, qis lipoprotein tsawg (HDL) cholesterol, nrog rau tag nrho cov siab, siab tsis-HDL, siab qis lipoprotein tsawg.cov roj cholesterol, thiab siab apolipoprotein B) tau ntawm nws tus kheej thiab kev txheeb cais tseem ceeb cuam tshuam rau cov tuab cpRNFLT. Hauv qhov sib piv, peb tsis pom muaj kev sib koom ua ke tseem ceeb ntawm cpRNFLT thiab cov cim ntawm kev mob, qabzib homeostasis, lub siab ua haujlwm, ntshav siab, lossis rog hauv peb cov kev soj ntsuam tshwj xeeb thiab thoob ntiaj teb. Cov ntsiab lus: Cov cim ntawm lub raum ua haujlwm thiab cov lipid metabolism yog cov kwv yees ntawm kev ua haujlwm cpRNFLT hauv kev tshawb fawb loj thiab sib sib zog nqus cov pej xeem raws li nws tus kheej ntawm yav tas los tsim covariates. Cov kev tshawb fawb yav tom ntej ntawm cpRNFLT yuav tsum suav nrog cov biomarkers thiab yuav tsum tau tshawb xyuas seb kev koom ua ke yuav txhim kho qhov kev kuaj mob ntawm qhov muag thaum ntxov raws li cpRNFLT. Keywords: Retinal paj fiber txheej, Glaucoma, Biomarkers,Lub raum ua haujlwmOptical coherence tomography, Lipid profile, LDL cholesterol, HDL cholesterol, eGFR, Cystatin C, Apolipoprotein B, Apolipoprotein A1

Nyem qhov no kom paub ntau ntxiv

Keeb kwm

Retinal paj fiber txheej (RNFL) tsis xws luag yog cov cim ntxov ntawm glaucoma thiab optic disc deformation [1]. RNFL thickness yog, yog li ntawd, ib qho cuab yeej tseem ceeb hauv kev ntsuam xyuas ntawm glaucoma thiab lwm yam optic neuropathies [2]. Spectral-domain optical coherence tomography (SD-OCT) yog qhov tsim nyog [3], tsis muaj kev cuam tshuam, hauv vivo cov txheej txheem rau kev tsom xam ntawm cov hlab ntsha ntawm lub paj hlwb, thiab kev nce qib tsis ntev los no tau tso cai rau cov duab pom zoo rau circumpapillary RNFL thickness (cpRNFLT) [4]. Tsis ntev los no, cpRNFLT tau cuam tshuam nrog qhov sib txawv, yooj yim anthropometric, thiab biochemical ntsuas hauv kev tshawb fawb sib txawv. Piv txwv li, Ho et al. [5] Qhia txog kev koom tes zoo ntawm ntiaj teb cpRNFLT nrog cov lipoprotein tsawg (LDL)cov roj cholesterolthiab muaj kev cuam tshuam tsis zoo nrog kev mob ntshav qab zib ntau ntau hauv peb pawg neeg Esxias sib txawv. Tsis tas li ntawd, hnub nyoog thiab keeb kwm ntawm mob hlab ntsha tawg lossis kub siab tsis zoo, qhov kev haus luam yeeb tau zoo, muaj feem xyuam rau ntiaj teb cpRNFLT hauv kev txheeb xyuas qhov sib txawv ntawm yim European, cov kev tshawb fawb txog pej xeem [6]. Hauv qhov sib piv, Lamparter li al.[7] tsis pom muaj kev sib koom tes ywj pheej ntawm ntiaj teb cpRNFLT thiab kab mob plawv hauv ntau qhov kev txheeb xyuas hauv Gutenberg Health Study. Ua ke, lub koom haum ntawm ntiaj teb cpRNFLT qhia tau hais tias tsis sib haum xeeb nrog rau cov kab mob cardiometabolic xeev. Ua ntej txhais cov txheej txheem cpRNFLT mus rau hauv tsev kho mob, nws yog ib qho tseem ceeb uas yuav tau tshawb xyuas anthropometric, biochemical, thiab cov chaw kho mob tsis muaj peev xwm cuam tshuam rau cpRNFLT ywj siab ntawm lwm cov kev kwv yees zoo, piv txwv li, hnub nyoog, poj niam txiv neej, thiab scan radius. Tsis tas li ntawd, lwm yam tseem ceeb cuam tshuam rau cpRNFLT yuav tsum tau ua tib zoo txhais los pab qhov kev kuaj pom ntxov ntawm cov kab mob qhov muag thiab tiv thaiv kev tsis ncaj ncees ntawm cpRNFLT vim yog lwm cov chaw kho mob thiab biochemical biomarkers. Txawm li cas los xij, cov kev tshawb fawb yav dhau los ntawm cpRNFLT qhia txog cov kev txwv hauv qab no: lawv (a) suav nrog pawg ntawm cov qauv me me; (b) tau txheeb xyuas thoob ntiaj teb cpRNFLT tab sis tsis yog cov ntaub ntawv tshwj xeeb; (c) cais cov ncauj lus nrog cov kab mob cardiometabolic sib txawv, xws li, hom 2 ntshav qab zib lossis ntshav siab; (d) tsis suav nrog ntau yam ntawm anthropometric, biochemical, thiab cardiometabolic cov cim thiab lwm cov ntaub ntawv ntawm tus neeg mob; thiab (e) tsis tau siv cov qauv hloov kho ntau yam sib txawv los tshawb xyuas cov kev kwv yees ywj pheej ntawm cpRNFLT.

Peb, yog li ntawd, tau tshawb xyuas ntau lub vaj huam sib luag ntawm ntau yam anthropometric thiab cardiometabolic biomarkers thiab ntau qhov chaw kho mob phenotypes thiab lawv cov koom haum nrog cov haujlwm tshwj xeeb cpRNFLT profile ntsuas los ntawm SD-OCT hauv qhov loj (N=8952 cov ntsiab lus), tsis raug xaiv , thiab sib sib zog nqus phenotyped pej xeem-raws li kev tshawb fawb nyob rau hauv lub teb chaws Yelemees. Peb tau siv cov txheej txheem ophthalmologic thiab non-ophthalmologic kev tshawb nrhiav thiab kev txheeb cais nrog kev kho rau ntau yam kev kuaj.

Cov neeg koom nrog txoj kev

Qhov kev tshuaj ntsuam no yog ib feem ntawm cov pej xeem-based LIFE-Adult Study ua los ntawm Leipzig Research Center for Civilization Diseases ntawm Leipzig University thaum lub Yim Hli 2011 thiab Kaum Ib Hlis 2014 [8]. Txoj Kev Kawm LIFE-Adult Study suav nrog 10,000 random xaiv cov neeg koom los ntawm cov pej xeem sau npe tsuas yog ib nrab lab tus neeg nyob hauv Leipzig, lub nroog nyob rau sab hnub tuaj ntawm lub teb chaws Yelemees.

Txoj Kev Tshawb Fawb LIFE-Adult Study tau ua raws li hnub nyoog-thiab kev sib deev-stratified feem ntau tsom rau cov neeg uas muaj hnub nyoog ntawm 40 thiab 79 xyoo [8]. Rau lub hom phiaj no, tag nrho cov pej xeem muaj 9600 yam ntawm 40 thiab 79 xyoo, nrog rau 400 yam ntawm 19 thiab 39 xyoo. Txhua lub hnub nyoog ncua sij hawm (los ntawm kaum xyoo) tau sib npaug nrog kev hwm ntawm cov ncauj lus thiab kev sib deev. Txoj kev tshawb no tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Ncaj Ncees ntawm Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob ntawm Leipzig University (tus naj npawb pom zoo: 263-2009-14122009) thiab ua raws li Kev Tshaj Tawm ntawm Helsinki thiab tag nrho tsoomfwv thiab lub xeev txoj cai. Ua ntej yuav suav nrog, tau txais kev pom zoo sau los ntawm txhua tus neeg koom.

Cov ntaub ntawv sau / suav nrog thiab cais tawm cov txheej txheem

Thaum lub sij hawm ntsuam xyuas hauv paus, cov neeg koom nrog kev tshawb fawb tau sib sib zog nqus phenotyped, nrog rau cov ntaub ntawv ophthalmological duab, kev xam phaj, cov lus nug, kev kuaj lub cev, thiab kuaj ntshav thiab zis [8]. Raws li ib feem ntawm kev soj ntsuam ophthalmic, SD-OCT imaging (Spectralis, Heidelberg Engineering, Heidelberg, Lub teb chaws Yelemees) tau ua, yielding cpRNFLT scans ib ncig ntawm lub paj hlwb. Qhov chaw ntawm cpRNFLT lub voj voog thiab kev sib koom ua ke tau piav qhia yav dhau los [4]. Peb tsis suav cov kev kawm uas ploj lawm SD-OCT scans (tsis suav N=931) lossis SD-OCT scans siv cov qauv hauv qab no: (1) B-scan tus lej hauv ib qhov chaw<50,(2)signal to="" noise=""><20 db,="" and(3)="" missing="" or="" unreliable="" rnflt="" a-scans="">5%(excluded N = 117). For the remaining 8952 subjects, one eye was randomly selected if both eyes of an included subject were reliable [4]. For validation analyses, we classified optic nerve head (ONH) abnormalities if any of the following were present: excavation (suspected glaucoma [i.e., violation of the inferior-superior-nasal-temporal rule, vertically oval with cup-to-disc ratio>0.7], optic disc pit, los yog coloboma ntawm optic disc), optic disc hemorrhage, neovascularization, optic atrophy, sectoral paleness, ONH o, papilledema, los yog optic disc drusen [4]. Tsis tas li ntawd, tus neeg mob cov ntaub ntawv ntawm kev kuaj mob yav dhau los ntawm glaucoma, nrog rau cov tshuaj glaucoma, tau sau tseg.

Anthropometric thiab biochemical markers

Classical anthropometric (piv txwv li, lub cev qhov Performance index [BM], lub duav thiab lub duav ncig, ntshav siab) tau soj ntsuam raws li cov txheej txheem txheej txheem los ntawm cov kws kho mob kawm. Hauv txhua qhov kev kawm, kev kuaj ntshav yoo mov tau raug coj los ua ntu zus thiab ib lub rooj sib tham ntawm kev kuaj sim tau ua nyob rau hnub ntawm cov qauv sau [8]. Cov biomarkers ntawm lub vaj huam sib luag tau piav qhia yav dhau los [8] thiab suav nrog kev ntsuas ntawm tag nrho cov roj cholesterol, siab lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides (TG), apolipoprotein (apo) B, apoAl, lipoprotein (Lp)(a), qabzib, insulin, glycated hemoglobin (HbAlc), lub siab enzymes, interleukin -6, siab C-reactive protein (hsCRP), cystatin C, thiab tso zis albumin thiab creatinine, tag nrho cov raug txiav txim siab. nyob rau hauv lub hauv paus lab los ntawm cov txheej txheem [8]. Hauv txhua qhov kev kawm, qhov kwv yees glomerular filtration rate (eGFR) tau suav nrog siv cystatin C-raws li mob raum kab mob (CKD) kab mob sib kis sib koom ua ke [9]. Raws li lub hom phiaj ntawm txoj kev tshawb fawb tam sim no yog los tshawb xyuas cov koom haum ntawm ntau cov cim kev pheej hmoo cardiometabolic thiab cpRNFLT, peb tau siv tsuas yog cystatin C-raws li kev sib npaug uas tau tshaj tawm tsis ntev los no yog qhov sib npaug zoo tshaj plaws rau kev ntsuas kev pheej hmoo plawv [10]. CKD raws li txoj cai tau txhais tias yog cov zis albumin / creatinine piv ntau dua lossis sib npaug li 30 mg / g thiab / lossis de-creased eGFR<60 ml/min/1.73="" m²,="" and="" the="" cohort="" was="" divided="" into="" five="" egfr="" categories(i.e.,="" g1-g5="" combining="" g3a="" and="" g3b="" into="" one="" g3="" category),="" as="" well="" as="" four="" ckd="" risk="" categories="" (i.e.,="" low,="" moderately="" increased,="" high,="" and="" very="" high="" risk),="" according="" to="">

Kev txheeb cais

Txhua qhov kev txheeb xyuas txheeb cais tau ua nyob rau hauv R ib puag ncig siv version 3.5 (R Foundation for Statistical Computing, Vienna, Austria). Rau kev sib piv ntawm cov poj niam thiab cov txiv neej cov ntsiab lus, qhov tsis sib xws Cov Tub Ntxhais Kawm t-test (rau qhov sib txawv tsis tu ncua) los yog chi-squared xeem (rau categorical variables) tau siv, raws li.

Raws li cov kauj ruam tom ntej, peb tau tshuaj xyuas cov koom haum ntawm ntau yam anthropometric, nrog rau cardiometabolic, bio-markers ntawm sectoral RNFLT. Rau lub hom phiaj no, multivariable linear regression tsom xam tau ua rau tus neeg cim hloov kho hnub nyoog, poj niam txiv neej, thiab scanning vojvoog vojvoog hauv txhua tus qauv. Siv cov kev sib txawv no raws li kev ywj pheej sib txawv hauv cov qauv, kev koom tes ntawm txhua tus cim nrog sectoral cpRNFLT (dependent variable) raug xam cais rau lub cev (T), superior-temporal (TS), superonasal (NS), qhov ntswg (N), inferonasal (NI), thiab inferotemporal (TI) sectors, thiab thoob ntiaj teb (G).

Lub vojvoog scanning tau suav nrog qhov sib txawv ntawm txhua tus qauv txij li lub qhov muag loj thiab cov yam ntxwv kho qhov muag ntawm tib neeg lub lens confound cpRNFLT ntsuas [12-14]. Qhov tseeb scanning lub voj voog vojvoog (mm) yog kwv yees los ntawm kev tsom xam siv los ntawm lub tshuab Spectralis, raws li tus qauv siv dav [15]. Raws li poj niam txiv neej [4] thiab hnub nyoog [14] tau pom tias muaj kev cuam tshuam rau cpRNFLT, cov cim no kuj tau suav nrog cov kev ywj pheej ntawm txhua tus qauv.

Peb tom ntej no nrhiav los sib piv cov txheeb ze lub zog ntawm cov koom haum ntawm tag nrho cov biomarkers nrog sectoral cpRNFLT. Yog li ntawd, ib lub sectoral thiab thoob ntiaj teb heatmap ntawm standardized qhov tseem ceeb los ntawm multivariable tsom xam rau txhua sectoral cpRNFLT yog tsim rau tag nrho cov biomarkers, thiab standardized qhov tseem ceeb tau ua hauj lwm nyob rau hauv daim duab cov xim code sawv cev lub zog ntawm txhua lub koom haum.

Raws li kev soj ntsuam rhiab heev, peb ntxiv cov txiaj ntsig ntawm qhov kev ntsuam xyuas kab rov ua dua rau cov cim lipid nrog cov txheej txheem cpRNFLT los ntawm kev sib koom ua ke rau hauv cov ncauj lus ntawm kev kho statin piv rau cov neeg siv tsis yog statin. Rau lub hom phiaj no, peb siv Anatomical Therapeutic Chemical (ATC) kev faib cov lej los rho tawm cov neeg koom nrog kho nrog 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (ie, statins), yog li txo cov roj cholesterol synthesis. Txhawm rau tshawb xyuas qhov muaj peev xwm kho kom haum xeeb ntawm kev haus luam yeeb ntawm kev koom tes ntawm cpRNFLT thiab covlipid profile, the Bayesian information criterion difference(ABIC)was computed for model comparisons. For this purpose, two different linear regression models were calculated with age, sex, measurement radius, and the respective lipid marker, as regressors (model A), as well as an additional model comprising of model A+smoking status(model B). The BIC difference(ABIC) was calculated by △BIC= BICmo-del A-BICmodel B. An ABIC>2 tau suav tias yog qhov muaj feem cuam tshuam raws li Madrigal-Gonzalez li al. [16], as well as Kass and Raftery [17].

Nyob rau hauv tag nrho lwm yam kev ntsuam xyuas, ap tus nqi<0.05 was="" considered="" statistically="" significant.="" the="" false="" discovery="" rate(fdr)method="" was="" applied="" to="" correct="" all="" p="" values="" for="" multiple="">

Fig.1 Heatmap of standardized coefficients for all researched biomarkers and global, as well as sectoral, circumpapillary retinal paj fiber txheej thickness (qpRNFLT. Separate multivariable linear regression analys was aired out for each of the biomarkers (independent variable) thiab cov sectoral los yog ntiaj teb cpRNFLT (dependent variable).Txhua tus qauv sib txawv tau hloov kho rau hnub nyoog, poj niam txiv neej, thiab scanning voj voog vojvoog Qhov kev tshawb pom tsis tseeb yog siv los kho p qhov tseem ceeb rau ntau qhov sib piv. qhia tau hais tias tus qauv tsis siv tau nyob rau hauv cov sector no), ib tug dawb (kub) square yog depicted.Rau tag nrho cov tseem ceeb sectors, lub zog, raws li kev soj ntsuam los ntawm standardized B, raws li zoo raws li cov kev taw qhia, ntawm cov koom haum, yog xim-coded. , qhov zoo (hauv xim liab / sov sov), thiab qhov tsis zoo (hauv xim xiav / txias) cov koom haum yog ntxoov ntxoo raws li cov qauv sib txawv coefficients Abbreviations A LAT, alanine aminotransferase, alkaline phosphatase ApoA1. apolipoprotein A1; ApoB, apolipoprotein B; ASAT aspartate aminotransferase; BMI, lub cev hnyav index; CKD, mob raum mob; DBP, diastolic ntshav siab; eGFR, cystatin C-raws li kwv yees glomerular pom tus nqi; GGT, gamma-glutamyl transferase; HbAIc, glycated hemoglobin AIc; HDL high-density lipoprotein; hsCRP, siab-rhiab heev C-reactive protein; IL interleukin, LDL, qis lipoprotein; Lp(a), lipoprotein(a); SBP, systolic ntshav siab; TG, triglycerides; WHR lub duav-rau-hip ratio. Optic paj hlwb sectors; N, nasal sector NL inferonasal sector: NS. superonasal sector. , temporal sector: Jl, infero-temporal sector TS, supero-temporal sector; G, alobal (txhais tau tias tag nrho)

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