Abstract: Circulating osteoprotegerin (OPG) yog biomarker rau cov kab mob plawv uas cuam tshuam nrog cov kab mob raum ntev (CKD). Txhawm rau tshawb xyuas qhov sib koom ua ke ntawm OPG theem nrog kev mus ntsib mus ntev-rau-mus saib ntshav siab hloov pauv (BPV) hauv cov neeg mob ua ntej CKD, tag nrho ntawm 1855 cov kev kawm nrog CKD los ntawm theem 1 mus rau pre-dialysis theem 5 los ntawm tus neeg yuav los tom ntej. pawg tau txheeb xyuas. Kev mus ntsib mus ntev BPV tau txiav txim siab los ntawm qhov nruab nrab qhov sib txawv (ARV), tus qauv sib txawv (SD), thiab coefficient of variation (CoV) ntawm systolic thiab diastolic ntshav siab (SBP thiab DBP). ARV ntawm SBP (Hloov coefficient 0.143, 95 feem pua ​​​​kev ntseeg siab lub sijhawm 0.021 txog 0.264) tau cuam tshuam nrog cov ntshav OPG. Txawm hais tias SD thiab CoV ntawm SBP tsis cuam tshuam nrog cov ntshav OPG qib hauv kev tshuaj ntsuam xyuas ntau yam kab rov tav, txwv cubic spline pom qhov kev sib raug zoo ntawm cov ntshav OPG qib nrog tag nrho ntawm ARV, SD, thiab CoV. Kev sib koom ua ke ntawm cov ntshav OPG qib thiab DBP hloov pauv tsis yog qhov tseem ceeb. Cov pab pawg neeg soj ntsuam tau qhia tias kev koom tes ntawm cov ntshav OPG nrog BPV yog qhov tseem ceeb hauv cov kev kawm nrog Charlson comorbidity Performance index tsawg dua lossis sib npaug rau 3 thiab hauv cov kev kawm uas tsis muaj keeb kwm ntawm ntshav qab zib mellitus. Hauv kev xaus, circulating OPG theem muaj feem cuam tshuam nrog kev mus ntsib BPV mus sij hawm ntev hauv cov neeg mob ua ntej CKD.

Raws li cov kev tshawb fawb muaj feem xyuam, cistanche yog ib txwm suav tshuaj ntsuab uas tau siv rau ntau pua xyoo los kho ntau yam kab mob. Nws tau raug pov thawj scientific kom muaj cov tshuaj tiv thaiv kab mob, tiv thaiv kev laus, thiab antioxidant zog. Cov kev tshawb fawb tau pom tias cistanche muaj txiaj ntsig zoo rau cov neeg mob uas muaj kab mob raum. Cov khoom xyaw nquag ntawm cistanche paub tias txo qhov mob, txhim kho lub raum ua haujlwm thiab rov ua kom lub raum tsis zoo. Yog li, kev sib koom ua ke cistanche hauv txoj kev npaj kho mob raum tuaj yeem muab txiaj ntsig zoo rau cov neeg mob hauv kev tswj hwm lawv tus mob. Cistanche pab txo qis proteinuria, txo qis BUN thiab creatinine qib, thiab txo qhov kev pheej hmoo ntawm lub raum puas. Tsis tas li ntawd, cistanche kuj pab txo cov roj cholesterol thiab triglyceride uas tuaj yeem ua rau muaj kev phom sij rau cov neeg mob uas muaj kab mob raum.

Nyem rau ntawm Cistanche Tubulosa Ntxiv

【Yog xav paub ntxiv: david.deng@wecistanche.com / WhatApp:86 13632399501 】

1. Taw qhia

Ntshav siab variability (BPV) yog ib qho kev tshwm sim ntawm kev mob plawv (CV) cov txiaj ntsig, raws li nws kwv yees qhov kev pheej hmoo ntawm CV cov xwm txheej thiab tag nrho cov neeg tuag nyob rau hauv cov pej xeem [1-3], ywj siab ntawm cov ntshav siab (BP). Ntawm cov neeg mob uas muaj kab mob raum ntev (CKD), mus ntsib BPV mus sij hawm ntev kuj tseem cuam tshuam nrog cov txiaj ntsig CV tsis zoo [4]. Tsis tas li ntawd, mus ntsib BPV ua rau muaj kev pheej hmoo ntawm qhov xwm txheej CKD hauv cov neeg mob ntshav siab [5] thiab ua kom lub raum tsis ua haujlwm hauv cov neeg mob CKD [6-8]. Muab hais tias CV cov xwm txheej yog qhov ua rau tuag rau cov neeg mob uas txo lub raum ua haujlwm [9], qhov kev kwv yees ntawm BPV mus sij hawm ntev tau dhau los ua qhov tseem ceeb hauv kev tswj hwm cov neeg mob CKD.

Osteoprotegerin (OPG) yog decoy receptor ntawm receptor activator ntawm nuclear factor kappa-B ligand (RANKL) [10], uas belongs rau lub soluble qog necrosis yam superfamily receptor [11]. OPG inhibits RANKL-mediated sib txawv ntawm osteoclasts nrog rau kev ua kom thiab ciaj sia ntawm cov laus osteoclasts [11], ua si lub luag haujlwm tseem ceeb hauv kev tswj cov pob txha hloov pauv. Circulating OPG qib nce nrog kev pib ntawm kev noj zaub mov atherogenic, thaum exogenous OPG txhaj tshuaj tiv thaiv vascular calcification [12-14], qhia tias circulating OPG raws li biomarker, tab sis tsis yog tus neeg nruab nrab, ntawm atherosclerosis uas tseem cuam tshuam nrog CKD. Cov kev tshawb fawb yav dhau los tau pom tias qib OPG cov ntshav siab tau cuam tshuam nrog qhov muaj [15] thiab qhov hnyav [16] ntawm cov hlab ntsha hauv cov hlab ntsha hauv cov neeg mob CKD. Nyob rau hauv no hais txog, nce circulating OPG theem tau raug npaj los ua tus kwv yees ntawm cov hlab plawv [17,18] thiab tag nrho-ua rau [19,20] kev tuag hauv cov neeg mob CKD. Qib OPG muaj txiaj ntsig zoo nrog cov kab mob peripheral artery, arterial txhav, thiab arterial calcification nyob rau hauv cov neeg mob uas muaj kab mob raum kawg [21–24]. Tsis tas li ntawd, kev hloov hauv lub raum txo qis qis ntawm OPG [25], thiab kev hloov pauv thaum ntxov tom qab hloov pauv OPG theem hauv cov ntshav tau kwv yees cov neeg mob muaj sia nyob ntev mus txog 8 xyoo [26], sib sau qhia txog kev cuam tshuam txog kev ncig ntawm OPG qib hauv cov neeg mob. lub raum insufficiency. Txawm li cas los xij, kev sib koom ua ke ntawm cov qib OPG thiab BPV tseem tsis tau lees paub, tshwj xeeb tshaj yog cov neeg mob CKD.

Peb nyob ntawm no tau tshawb xyuas qhov kev koom tes ntawm kev nthuav dav OPG theem nrog rau mus sij hawm ntev-mus-mus ntsib BPV hauv cov neeg mob uas muaj ntshav qab zib CKD. Ua kom zoo dua ntawm ntau yam BPV indices, peb nquag tshuaj xyuas cov kab sib txuas ntawm cov ntshav OPG qib thiab BPV. Peb kuj tau ua cov kev tshuaj ntsuam xyuas pab pawg los hais seb puas yog kev koom tes ntawm cov ntshav OPG qib nrog BPV tau hloov kho los ntawm cov ntsiab lus kho mob.

2. Cov ntaub ntawv thiab cov txheej txheem

2.1. Kawm Tsim

Txoj Kev Kawm Kaus Lim Kauslim rau cov txiaj ntsig ntawm Cov Neeg Mob Mob Raum Kab Mob (KNOW-CKD) yog ib txoj kev tshawb fawb thoob tebchaws uas muaj feem nrog 9 lub tsev kho mob tertiary-care general hauv Kauslim [27]. Kauslim cov neeg mob uas muaj CKD los ntawm theem 1 mus rau pre-dialysis theem 5, uas yeem muab kev tso cai qhia tau rau npe. Txoj kev tshawb no tau ua los ntawm cov hauv paus ntsiab lus ntawm Kev Tshaj Tawm ntawm Helsinki, thiab txoj kev tshawb fawb raws tu qauv tau pom zoo los ntawm cov koom haum tshuaj xyuas pawg thawj coj ntawm cov chaw koom. Tag nrho ntawm 2238 cov ntsiab lus tau ua raws li qhov ntev. (Daim duab 1). Tom qab tsis suav nrog cov uas tsis muaj qhov ntsuas hauv paus ntawm BP, cov uas muaj ntau qhov kev ntsuas BP thaum lub sijhawm ua raws li tsawg dua peb zaug, thiab cov uas tsis muaj qhov ntsuas hauv qab ntawm cov ntshav OPG, tag nrho ntawm 1855 cov ntsiab lus thaum kawg suav nrog hauv kev tshuaj ntsuam. Lub sijhawm nruab nrab ntawm kev soj ntsuam yog 6.124 xyoo.

2.2. Cov ntaub ntawv sau los ntawm cov neeg koom

Cov ntaub ntawv pej xeem tau sau los ntawm txhua tus neeg koom nrog, suav nrog hnub nyoog, poj niam txiv neej, cov xwm txheej tsis sib xws, thiab keeb kwm tshuaj (angiotensin-hloov enzyme inhibitor / angiotensin II receptor blockers (ACEi / ARBs), diuretics, tag nrho cov tshuaj tiv thaiv ntshav siab, statins). Cov neeg ua haujlwm cob qhia tau ntsuas qhov siab thiab qhov hnyav ntawm cov neeg koom nrog kev kawm. Lub cev qhov Performance index (BMI) yog xam raws li qhov hnyav muab faib los ntawm qhov siab squared. Cov qauv venous tau sau tom qab kev yoo mov ib hmos, txhawm rau txiav txim siab hemoglobin, albumin, tag nrho cov roj cholesterol, qis lipoprotein cholesterol (LDL-C) high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), yoo mov qabzib, siab C. -reactive protein (hs-CRP), 25-hydroxyvitamin D (25(OH) vitamin D) thiab qib creatinine ntawm lub hauv paus. Qhov kwv yees glomerular filtration rate (eGFR) yog xam los ntawm Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [28]. Cov zis albumin-rau-creatinine piv tau ntsuas hauv random, nyiam dua thib ob-voided, pom cov zis kuaj. Nees nkaum-plaub-teev tso zis protein excretion kuj tau txiav txim.

2.3. Kev ntsuas ntawm Serum OPG Concentration

Ntshav OPG qib tau ntsuas los ntawm kev siv cov khoom siv tshuaj tiv thaiv kab mob enzyme-linked immunosorbent (BioVendor R&D, Brno, Czech koom pheej) hauv lub chaw kuaj mob hauv nruab nrab (Lab Genomics, Seongnam, Kauslim) [29]. Intra-assay coefficients ntawm variations tau<4.9% and inter-assay coefficients of variations were <9.0%. Mean values of the duplicated assay were used for reporting results.

2.4. Kev txiav txim siab mus sij hawm ntev mus ntsib BPV

BP tau ntsuas los ntawm lub tshuab hluav taws xob sphygmomanometer tom qab zaum so rau 5 feeb, ntawm 0, 6, thiab 12 lub hlis thiab tom qab ntawd txhua xyoo tom qab ntawd mus txog 8 xyoo. Kev mus ntsib mus ntev-mus-mus saib BPV tau txiav txim siab los ntawm qhov nruab nrab qhov sib txawv (ARV), tus qauv sib txawv (SD), thiab coefficient of variation (CoV) ntawm systolic thiab diastolic BP (SBP thiab DBP) hla kev mus ntsib. Tus naj npawb nruab nrab ntawm BP ntsuas hauv cov neeg koom nrog kev tshawb fawb yog 7 zaug.

2.5. Kev Kawm Txuj Ci

Kev hloov pauv hauv ARV (hauv mmHg), SD (hauv mmHg), thiab CoV ntawm SBP thiab DBP los ntawm serum OPG qib (hauv pmol/L) tau txheeb xyuas. ARV ntawm SBP tau siv rau hauv thawj qhov kev tshuaj ntsuam, vim nws qhov kev sib raug zoo nrog cov ntshav OPG yog qhov muaj zog tshaj plaws (Pearson r {{0}}}.195, p < 0.001), thaum lwm tus tau siv rau hauv qhov kev ntsuam xyuas theem nrab.

2.6. Kev txheeb cais

Cov kev hloov pauv tsis tu ncua tau qhia tias txhais tau tias ± tus qauv sib txawv lossis nruab nrab [interquartile range]. Categorical variables tau qhia raws li tus naj npawb ntawm cov neeg koom thiab feem pua. Rau kev txheeb xyuas piav qhia, Cov Tub Ntxhais Kawm T-test lossis ib-txoj kev tsom xam ntawm qhov sib txawv thiab χ2 xeem tau siv rau qhov sib txawv thiab categorical sib txawv raws li. Cov ncauj lus uas muaj cov ntaub ntawv ploj lawm raug tshem tawm los ntawm kev tshuaj xyuas ntxiv. Multivariate linear regression analyses tau siv los txheeb xyuas cov kev sib raug zoo ntawm qib OPG thiab BPV. Cov qauv tau hloov kho rau hnub nyoog, poj niam txiv neej, Charlson comorbidity Performance index, haus luam yeeb keeb kwm, BMI, SBP, DBP, tshuaj (ACEi/ARB, diuretic siv, tus naj npawb ntawm cov tshuaj tiv thaiv hypertensive, statins), hemoglobin, albumin, HDL-C, yoo mov qabzib, 25 (OH) vitamin D, qib hs-CRP, eGFR thiab 24 teev cov zis protein. Cov txiaj ntsig ntawm multivariate linear regression qauv tau nthuav tawm raws li beta coefficient thiab 95 feem pua ​​​​CIs. Kev txwv qhov cubic splines tau siv los pom kev sib koom ntawm cov ntshav OPG qib raws li qhov sib txawv tsis tu ncua thiab hloov kho beta coefficients rau BPV indices. ob sab p tus nqi<0.05 were considered statistically significant. Statistical analysis was performed using SPSS for Windows version 22.0 (IBM Corp., Armonk, NY, USA) and R (version 4.1.1; R Project for Statistical Computing, Vienna, Austria).

3. Cov txiaj ntsig

3.1. Cov yam ntxwv tseem ceeb

Txhawm rau hais txog cov yam ntxwv hauv paus, cov neeg koom nrog kev kawm tau muab faib ua quartile los ntawm qib OPG (Table 1). Qhov nruab nrab hnub nyoog qis tshaj thiab siab tshaj nyob rau hauv 1st (Q1) thiab 4th (Q4) quartiles, ntsig txog. Inversely, qhov zaus ntawm txiv neej pw yog siab tshaj nyob rau hauv Q1. Feem ntau ntawm cov kev kawm hauv Q1 (94.8 feem pua) tau koom nrog Charlson cov khoom lag luam Performance index Tsawg dua lossis sib npaug rau 3, thaum lub sijhawm ntawm cov khoom nrog Charlson cov khoom lag luam Performance index Ntau dua lossis sib npaug rau 4 yog qhov siab dua hauv Q4. Qhov zaus ntawm cov kev kawm uas muaj keeb kwm yav dhau los ntawm DM thiab cov kab mob coronary artery tau nce siab dua hauv Q4, thaum tsis muaj qhov sib txawv ntawm qhov zaus ntawm keeb kwm ntawm arrhythmia thiab kev haus luam yeeb ib txwm nyob ntawm pawg quartile. Qhov feem pua ​​​​ntawm cov neeg mob nrog DM tau nce ntxiv raws li qib OPG cov ntshav nce ntxiv, qhov feem pua ​​​​ntawm cov neeg mob nrog glomerulonephritis lossis polycystic raum kab mob txo qis thaum cov ntshav OPG nce. Txawm hais tias qhov zaus ntawm kev siv ACEi / ARB tsis txawv ntawm cov pab pawg, kev siv cov tshuaj diuretics, kev siv tsis tsawg tshaj li peb cov tshuaj tiv thaiv kab mob siab, thiab cov tshuaj statin tau pom ntau zaus hauv Q4. BMI tsis sib txawv ntawm cov pab pawg ib yam nkaus. SBP maj mam nce los ntawm Q1 mus rau Q4, thaum DBP, txawm tias qhov sib txawv tseem ceeb ntawm cov pab pawg, tsis tau qhia meej txog kev sib raug zoo nrog qib OPG. hemoglobin thiab albumin qib siab tshaj plaws thiab qis tshaj hauv Q1 thiab Q4, feem. Tag nrho cov roj cholesterol, LDL-C, thiab TG qib siab tshaj hauv Q4, thaum HDL-C qib qis tshaj hauv Q4. Kev yoo mov qabzib thiab qib hs-CRP tau siab tshaj hauv Q4, thaum 25 (OH) vitamin D qib qis tshaj hauv Q4. Ob leeg proteinuria hauv 24 teev tso zis thiab albumin-to-creatinine piv hauv cov zis yog siab tshaj hauv Q4. eGFR kuj tseem qis dua hauv Q4. Yog li, cov kev kawm uas muaj qib siab dua ntawm CKD tau pom ntau zaus hauv Q4. Ua ke, cov ntshav OPG qib siab tau cuam tshuam nrog kev kho mob tsis zoo hauv cov neeg mob CKD.

3.2. Lub koom haum ntawm Serum OPG Qib nrog BPV hauv Cov Neeg Mob nrog CKD

Txhawm rau sib piv SBP qhov sib txawv ntawm pawg quartile los ntawm cov ntshav OPG, ib txoj kev tsom xam ntawm qhov sib txawv tau ua (Daim duab 2). Tag nrho ARV, SD, thiab CoV ntawm SBP tau nce ntau ntxiv thaum cov ntshav OPG nce ntxiv. ARV thiab CoV ntawm DBP kuj siab tshaj hauv Q4 (Figure S1). Txhawm rau txiav txim siab txog kev ywj pheej ntawm cov ntshav OPG qib thiab systolic BPV, cov qauv sib txawv ntawm cov kab rov tav tau raug tshuaj xyuas (Table 2). Hauv kev txheeb xyuas ntawm txhua yam kev kawm, ARV ntawm SBP (Kho coefficient 0.143, 95 feem pua ​​​​kev ntseeg siab lub sijhawm (CI) 0.{{10}}21 txog {{21} }.264, p=0. Kev sib koom ua ke ntawm cov ntshav OPG qib thiab DBP hloov pauv tsis tseem ceeb (Table S1), tsis hais txog BPV qhov ntsuas. Txhawm rau pom qhov kev sib raug zoo ntawm cov ntshav OPG qib thiab SBP qhov sib txawv, txwv qhov cubic splines tau tsim, uas qhia txog kev sib raug zoo ntawm cov ntshav OPG qib thiab ARV ntawm SBP (Daim duab 3). Txawm hais tias SD (Adjusted coefficient 0). {26}}, 95% CI 0. ), txwv qhov cubic splines qhia txog kev sib raug zoo (Daim duab S2).

3.3. Kev soj ntsuam rhiab heev

Txhawm rau ua pov thawj peb qhov kev tshawb pom, peb tau ua qhov kev soj ntsuam rhiab heev los ntawm kev tsis suav nrog cov ncauj lus nrog CKD theem 1 (n=312), uas suav tias yog ze rau lub raum ua haujlwm (Table 3). Multivariate linear regression analyzes qhia tau hais tias cov ntshav OPG qib tau ruaj khov thiab cuam tshuam nrog ARV ntawm SBP (Kho coefficient 0.143, 95 feem pua ​​​​CI 0.008 rau 0.277, p {{10}}038). Tsis tas li ntawd, txhawm rau tshem tawm cov neeg uas muaj peev xwm ua rau muaj kev pheej hmoo ntau dhau ntawm BPV vim qhov ntsuas BP tsis tshua muaj, peb tsuas yog suav nrog cov ntsiab lus nrog kev ntsuas BP tsis pub tsawg dua 5 zaug (n=1502) thiab txheeb xyuas cov koom haum ntawm cov ntshav OPG qib thiab BPV. Txawm hais tias txo tus naj npawb ntawm cov ntsiab lus raug txheeb xyuas, cov ntshav OPG qib tau muaj zog thiab cuam tshuam nrog SD (Kho coefficient 0.149, 95 feem pua ​​​​CI 0.034 txog {{37} }.264, p=0.011), and CoV (Adjusted coefficient 0.001, 95% CI 0 . 0.264, p=0.096), ntawm SBP (Table S2). Ntawm cov kev kawm nrog kev ntsuas BP tsis pub tsawg dua 5 zaug, ntshav OPG qib tsis cuam tshuam nrog ib qho ntawm ARV (Kho coefficient 0.071, 95 feem pua ​​​​CI -0.036 txog 0.178, p=0.196) , SD (Adjusted coefficient 0.072, 95% CI -0.010 to 0.155, p=0.086), and CoV (Adjusted coefficient 0.001, 95%) CI 0.000 to 0.002, p=0.055) ntawm DBP (Table S3). Zuag qhia tag nrho, cov kev soj ntsuam rhiab heev tau lees paub tias qib OPG cov ntshav muaj feem cuam tshuam nrog BPV hauv cov neeg mob ua ntej CKD.

3.4. Kev tsom xam pab pawg

Txhawm rau hais seb qhov kev sib koom ua ke ntawm cov ntshav OPG qib nrog BPV tau hloov kho los ntawm cov ntsiab lus kho mob, peb tau soj ntsuam pab pawg pawg. Cov subgroups tau stratified los ntawm hnub nyoog (<60 or ≥60 years), gender (male or female), Charlson comorbidity index (≤3 or ≥4), BMI (<23 or ≥23 kg/m2 ), history of DM (without or with), eGFR (≥45 or <45 mL/min/1.73m2 ), 24 h  urine protein (<200 or ≥200 mg/g). Although the association between serum OPG level and ARV of SBP was not significantly modified in any subgroups (Table 4), the association of serum OPG level with SD (Table 5) and CoV of SBP (Table S4) was significantly modified by Charlson comorbidity index and history of DM, suggesting that the association of serum OPG with BPV is more prominent in the subjects with Charlson comorbidity index ≤3 and in the subjects without a history of DM. The association between serum OPG level and ARV, SD, or CoV of DBP was not significantly modified in any subgroups (Tables S5–S7).

4. Kev sib tham

Hauv txoj kev tshawb fawb tam sim no, peb pom muaj kev koom tes tseem ceeb ntawm kev nthuav dav OPG qib thiab mus ntsib BPV mus sij hawm ntev hauv cov neeg mob ua ntej CKD. Kev sib koom ua ke ntawm circulating OPG qib nrog BPV yog tshwj xeeb tshaj yog nyob rau hauv cov kev kawm nrog Charlson comorbidity Performance index tsawg dua los yog sib npaug rau 3 thiab nyob rau hauv cov kev kawm tsis muaj keeb kwm ntawm DM.

Kev nce qib ntawm OPG cov ntshav hauv cov ntsiab lus nrog txo eGFR tau tshaj tawm yav dhau los [30]. Txawm hais tias muaj kev sib cav txog lub luag haujlwm ntawm circulating OPG nyob rau hauv cov kab mob atherosclerotic [31], ib txoj kev tshawb fawb tau qhia tias exogenous OPG kev kho mob ua rau endothelial thiab vascular smooth cell tsis ua hauj lwm los ntawm kev txhawb zus tau tej cov reactive oxygen hom, uas yuav underlies vascular injurious teebmeem nyob rau hauv tej yam kev mob xws li. Raws li kev kub siab [32], qhov phenotype ntawm OPG-knockout nas thaum kawg qhia tias circulating OPG raws li biomarker, es tsis yog tus neeg nruab nrab, ntawm atherosclerosis, raws li OPG-tsis muaj nas tsim thaum ntxov arterial calcification [33]. Hauv cov ntsiab lus no, kev sib koom ua ke ntawm cov ntshav OPG siab nrog cov hlab ntsha hauv plawv [15,16], thiab plawv plawv [17,18] thiab tag nrho-ua rau kev tuag [19,20] hauv cov neeg mob CKD tau pom zoo. Kev sib koom ua ke ntawm qib OPG cov ntshav nrog rau mus sij hawm ntev-mus-mus saib BPV nthuav tawm hauv txoj kev tshawb no qhia txog lub luag haujlwm tshiab ntawm kev nthuav tawm OPG raws li biomarker uas kwv yees tus neeg sawv cev ntawm CV txheej xwm. Nws yuav tsum tau piav qhia ntxiv seb lub koom haum tseem siv tau rau cov pej xeem lossis cov neeg mob uas muaj kab mob raum kawg.

Peb tsis tuaj yeem nthuav qhia cov txheej txheem meej ntawm kev sib koom ua ke ntawm kev nthuav dav OPG qib thiab BPV, txawm hais tias qhov kev piav qhia ua tau yog qhov cuam tshuam uas tau kho los ntawm cov hlab ntsha. Mounting pov thawj qhia tias cov ntshav OPG qib yog cuam tshuam nrog vascular calcification thiab arterial txhav nrog rau cov hlab ntsha coronary calcification [10,34,35]. Raws li cov hlab ntsha txha caj qaum muaj feem cuam tshuam nrog kev nce hauv BPV [36], nws tau kwv yees tias cov hlab ntsha tuaj yeem ua rau muaj kev sib haum xeeb ntawm cov qib OPG thiab BPV.

Cov txheej txheem rau kev ntsuam xyuas ntawm kev mus ntsib BPV yog qhov sib txawv. SD yog qhov yooj yim dua thiab tej zaum yuav siv tau ntau dua tab sis zoo li cuam tshuam nrog qhov nruab nrab ntawm kev ntsuas ntshav siab. Yog li, CoV, uas yog xam los ntawm kev faib tus nqi nruab nrab los ntawm SD, kuj tau siv los txiav txim xyuas BPV [37]. ARV, uas txhais tau tias yog qhov nruab nrab ntawm qhov sib txawv ntawm qhov kev ntsuas sib law liag, yog qhov muaj kev ntseeg siab dua thiab muaj txiaj ntsig zoo ntawm lub sijhawm sib txawv ntawm qhov sib txawv txawm tias muaj qhov piv txwv tsawg dua li SD [38], uas yog vim li cas ARV tau siv los ua thawj. tsom xam hauv txoj kev tshawb fawb tam sim no. Lwm qhov Performance index ntawm BPV yog qhov txawv txav ntawm qhov nruab nrab (VIM), uas yog xam raws li qhov tsis yog-linear regression [39]. Txawm hais tias VIM raug suav hais tias yog qhov ntsuas zoo dua ntawm BP qhov sib txawv dua li lwm qhov ntsuas vim tias VIM tsis cuam tshuam nrog cov ntshav siab. Txawm li cas los xij, VIM tsis raug soj ntsuam hauv qhov kev tshawb fawb no, vim tias muaj qhov sib txawv tseem ceeb ntawm VIM thiab lwm qhov ntsuas ntawm BPV (SD, CoV, thiab ARV) thiab vim nws tsis tshua muaj txiaj ntsig hauv kev tshuaj ntsuam xyuas [37].

Muaj ntau qhov kev txwv rau txoj kev tshawb no. Ua ntej, peb tsis tau txheeb xyuas seb qhov kev sib raug zoo ntawm kev ua haujlwm siab OPG thiab yav dhau los paub qhov tsis zoo CV cov txiaj ntsig tau kho los ntawm BPV siab. Qhov thib ob, txawm hais tias muaj kev sib koom ua ke ntawm kev nthuav dav OPG nrog BPV, cov txheej txheem meej yuav tsum tau hais ntxiv. Qhov thib peb, txawm hais tias cov txiaj ntsig tau qhia tias muaj kev sib koom ua ke ntawm cov ntshav OPG qib thiab BPV, qhov tseem tuaj yeem tsis suav nrog lwm yam uas tsis yog BPV yuav muaj qee qhov cuam tshuam rau qib OPG hauv cov ntshav, vim tias cov yam ntxwv hauv paus tau sib txawv los ntawm cov ntshav OPG qib. Plaub, raws li kev tshawb fawb pawg neeg no tau tso npe rau cov neeg Kauslim nkaus xwb, yuav tsum tau ceev faj kom nthuav tawm cov ntaub ntawv hauv txoj kev tshawb fawb tam sim no rau lwm tus neeg.

5. Cov lus xaus

Hauv kev xaus, peb tshaj tawm txog kev sib koom ua ke ntawm kev nthuav dav OPG qib thiab mus ntsib BPV mus sij hawm ntev hauv cov neeg mob ua ntej CKD. Kev sib koom ua ke ntawm circulating OPG qib nrog BPV yog tshwj xeeb tshaj yog nyob rau hauv cov kev kawm nrog Charlson comorbidity Performance index tsawg dua los yog sib npaug rau 3 thiab nyob rau hauv cov kev kawm tsis muaj keeb kwm ntawm DM.

Cov khoom siv ntxiv:Cov hauv qab no muaj nyob online ntawm https://www.mdpi.com/article/ 10.3390/jcm11010178/s1, Figure S1: Restricted cubic spline of serum OPG on SD and CoV of SBP, Table S1: Multivariate linear regression analysis of serum OPG qib (ib pmol/L) rau DBPV, Table S2: Multivariate linear regression tsom xam ntawm cov ntshav OPG qib (ib pmol/L) rau SBPV nyob rau hauv cov ntsiab lus nrog BP ntsuas tsis pub tsawg tshaj 5 zaug thaum lub sij hawm soj ntsuam, Table S3: Multivariate linear Regression analyses ntawm serum OPG qib (ib pmol/L) rau DBPV nyob rau hauv cov kev kawm nrog BP ntsuas tsis tsawg tshaj li 5 zaug thaum lub sij hawm soj ntsuam, Table S4: Multivariate linear regression tsom xam ntawm cov ntshav OPG qib (ib pmol/L) rau ARV ntawm SBP hauv ntau pawg, Table S5: Multivariate linear regression analyzes of serum OPG level (per pmol/L) for CoV of SBP in various subgroups, Table S6: Multivariate linear regression analysis of serum OPG level (per pmol/L) for ARV of DBP hauv ntau pawg sub.

Tus sau kev koom tes:Conceptualization, SHS; methodology, SHS, TRO thiab HSC; validation, CSK; kev soj ntsuam, SHS; Resources, K.-HO, JL, YKO, JYJ and KHC; kev sau ntawv—kev npaj ua ntej, SHS; sau ntawv- tshuaj xyuas thiab kho, SHS; kev pom, SHS; kev saib xyuas, EHB thiab SWK; kev tswj xyuas qhov project, SKM thiab SWK; Kev nrhiav nyiaj txiag, K.-HO, HSC thiab SWK Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Nyiaj txiag:Txoj haujlwm no tau txais kev txhawb nqa los ntawm Kev Tshawb Fawb Kev Tshawb Fawb tau nyiaj los ntawm Kaus Lim Kauslim Chaw Tiv Thaiv thiab Tiv Thaiv Kab Mob (tus lej nyiaj 2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E33016020, 3301602, 3301602, 01, 2016E3300202, thiab 2019E320100), thiab los ntawm National Research Foundation of Kauslim ( NRF) tau txais nyiaj los ntawm Tsoomfwv Kaus Lim Kauslim (MSIT) (NRF-2019R1A2C2086276).

Institutional Review Board Statement:Cov txheej txheem kawm tau pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm txhua qhov chaw kho mob (Seoul National University Hospital ({0}}), Seoul National University Bundang Tsev Kho Mob (B-1106/129–008), Yonsei University Severance Tsev Kho Mob (4-2011-0163), Kangbuk Sam-sung Medical Center (2011-01-076), Seoul St. Mary's Tsev Kho Mob (KC11OIMI0441), Gil Tsev Kho Mob (GIRBA2553), Eulji General Tsev Kho Mob (201105-01), Chonnam National Tsev Kho Mob University (CNUH-2011-092), thiab Tsev Kho Mob Busan Paik (11-091)).

Cov Lus Qhia Txog Kev Pom Zoo:Cov ntaub ntawv tso cai tau txais los ntawm txhua yam kev koom tes hauv txoj kev tshawb fawb.

Cov ntaub ntawv muaj nyob:Cov ntaub ntawv nyoos txhawb cov lus xaus ntawm tsab xov xwm no yuav muab los ntawm cov kws sau ntawv, yam tsis muaj kev tshwj tseg.

Kev lees paub:KNOW-CKD: Kawm Group Clinical Centers. Seoul National University, Curie Ahn, Kook-Hwan Oh, Dong Wan Chae, Ho Jun Chin, Hayne Cho Park, Seungmi Lee, Hyun Hwa Jang, thiab Hyun Jin Cho. Yonsei University, Severance Hospital, Kyu Hun Choi, Seung Hyeok Han, Tae Hyun Yoo, thiab Mi Hyun Yu. Kangbuk Samsung Medical Center, Kyubeck Lee, thiab Sooyeon Jin. Catholic University of Kauslim, Seoul St. Mary's Hospital, Yong-Soo Kim, thiab Sol Ji Kim. Gachon University, Gil Tsev Kho Mob, Wookyung Chung, Youkyoung Jang, thiab Ji Hye Park. Eulji University, Eulji General Tsev Kho Mob. Young-Hwan Hwang, Su-Ah Sung thiab Jeong Ok So. Chonnam University, Soo Wan Kim thiab Ji Seon Lee. Inje University, Pusan ​​Paik Hospital, Yeong Hoon Kim, Sun Woo Kang thiab Yun Jin Kim. Epidemiology thiab Biostatistics. Department of Preventive Medicine, Seoul National University College of Medicine, Byung-Joo Park, Sue Kyung Park, thiab Juyeon Lee. Coordinating Center. Medical Research Collaborating Center, Seoul National University Hospital thiab Seoul National University College of Medicine, Joongyub Lee, Dayeon Nam, Soohee Kang, thiab Heejung Ahn. Central Laboratory, Donghee Seo, Lab Genomics, Kauslim Teb, thiab Dae Yeon Cho, Lab Genomics, Kauslim. Biobank. Kauslim Biobank, Kaus Lim Kauslim Chaw Tiv Thaiv thiab Tiv Thaiv Kab Mob, Osong, Kaus Lim Kauslim. Kauslim Lub Chaw Tiv Thaiv thiab Tiv Thaiv Kab Mob, Dukhyoung Lee, Hyekyung Park (Tus Thawj Saib Xyuas Haujlwm), Eunkyeong Jung (Tus Thawj Saib Xyuas Haujlwm), Suyeon Jeong, Eunmi Ahn, thiab Sil-Hea Sung.

Cov ntaub ntawv

1. Eguchi, K.; Hoshide, S.; Schwartz, EJ; Shimada, K.; Kario, K. Mus ntsib-rau-mus ntsib thiab ambulatory ntshav siab hloov pauv raws li kev kwv yees ntawm cov xwm txheej mob plawv hauv cov neeg mob ntshav siab. Am. J. Hypertens. 2012, 25, 962–968. [CrossRef] [PubMed]

2. Muntner, P.; Sib, D.; Tonelli, M. Reynolds, K.; Arnett, DK; Oparil, S. Kev sib raug zoo ntawm kev mus ntsib-mus-mus saib qhov sib txawv hauv systolic ntshav siab thiab tag nrho-ua rau kev tuag ntawm cov pej xeem: Nrhiav los ntawm NHANES III, 1988 txog 1994. Ntshav siab 2011, 57, 160–166. [CrossRef] [PubMed]

3. Suchy-Dicey, AM; Wallace, ER; Mitchell, SV; Aguilar, M. Gottesman, RF; Rice, K.; Kronmal, R.; Psaty, BM; Longstreth, WT, Jr. Cov ntshav siab hloov pauv thiab muaj kev pheej hmoo ntawm txhua qhov ua rau tuag, qhov xwm txheej myocardial infarction, thiab xwm txheej mob stroke hauv txoj kev tshawb fawb txog kev mob plawv. Am. J. Hypertens. 2013, 26, 1210–1217. [CrossRef] [PubMed]

4. Mallamaci, F.; Minutolo, R.; Leonardis, D.; D'Arrigo, G.; Tripepi, G.; Rapisarda, F.; Cicchetti, T.; Maimon, ib.; Enia, G.; Postorino, M. ua al. Lub sij hawm mus ntsib mus rau tom chaw ua hauj lwm lub sij hawm ntev ntshav siab variability ua rau muaj kev pheej hmoo ntawm kev mob plawv tsis zoo nyob rau hauv cov neeg mob uas muaj kab mob raum ntev. Raum Int. 2013, 84, 381–389. [CrossRef] [PubMed]

5. Li, Y.; Li, D.; Nkauj, Y.; Gao, L.; Neeb, F.; Wang, IB; Liang, M.; Wang, G.; Li, J.; Zhang, YJ; ua al. Kev mus ntsib-mus-mus saib qhov sib txawv ntawm cov ntshav siab thiab kev loj hlob ntawm cov kab mob raum ntev hauv cov neeg mob hypertensive. Nephrol. Hu rau. Hloov. Xyoo 2020, 35, 1739–1746. [CrossRef] [PubMed]

6. Nias, J.; Lynch, AI; Tanner, RM; Simpson, LWM; Davis, IB; Rahman, M.; ib. Whelton, PK; Oparil, S.; Muntner, P. Mus ntsib-mus-mus saib qhov sib txawv ntawm BP thiab CKD Cov txiaj ntsig: Cov txiaj ntsig tau los ntawm ALLHAT. Clin. J. Am. Soc. Nephrol. 2016, 11, 471–480. [CrossRef] [PubMed]

7. Yokota, K.; Fukuda, M.; Matsui, Y.; Hoshide, S.; Shimada, K.; Kario, K. Kev cuam tshuam ntawm kev mus ntsib-mus-mus saib qhov hloov pauv ntawm cov ntshav siab ntawm kev ua haujlwm ntawm lub raum tsis zoo hauv cov neeg mob uas tsis yog mob ntshav qab zib mob raum. Hypertens. Res. 2013, 36, 151–157. [CrossRef] [PubMed]

8. Yokota, K.; Fukuda, M.; Matsui, Y.; Kev, K.; Kimura, K. Mus ntsib-mus-mus saib qhov sib txawv ntawm cov ntshav siab thiab lub raum ua haujlwm poob qis hauv cov neeg mob ntshav qab zib mob raum. J. Clin. Hypertens. 2014, 16, 362–366. [CrossRef]

9. Thompson, S.; James, M.; Wieb, N.; Hemmelgarn, IB; Manns, IB; Klarenbach, S.; Tonelli, M. Alberta Kidney Disease, N. Ua rau tuag rau cov neeg mob uas txo lub raum ua haujlwm. J. Am. Soc. Nephrol. 2015, 26, 2504–2511. [CrossRef]

10. Montañez-Barragán, A.; Gómez-Barrera, I.; Sanchez-Niño, MD; Ucero, AC; González-Espinoza, L. Ortiz, A. Osteoprotegerin thiab kab mob raum. J. Neeb. 2014, 27, 607–617. [CrossRef]

11. Simonet, WS; Lacey, DL; Dunstan, CR; Kelley, M.; ib. Chang, MAS; Lus, R.; Nguyen, HQ; Ntoo, S.; Bennett, L.; ib. Boone, T.; ua al. Osteoprotegerin: Ib qho tshiab secreted protein koom nrog hauv kev tswj cov pob txha ceev. Cell 1997, 89, 309–319. [CrossRef]

12. Morony, S.; Tug, Y.; Zhang, Z.; Cattley, RC; Van, G.; Daws, D.; Stolina, M.; ib. Kostenuik, PJ; Demer, LL Osteoprotegerin inhibits vascular calcification yam tsis muaj kev cuam tshuam atherosclerosis hauv cov laus (-/-) nas. Xyoo 2008, 117, 411–420. [CrossRef]

13. Bennett, BJ; Scatena, M.; Kirk, UA; Ratzzi, M.; Varon, RM; Averill, M.; ib. Schwartz, NWS; Giachelli, CM; Rosenfeld, ME Osteoprotegerin inactivation accelerates atherosclerotic lesion progression thiab calcification nyob rau hauv cov laus ApoE-/- nas. Arterioscler. Thromb. Vasc. Biol. 2006, 26, 2117–2124. [CrossRef]

14. Weiss, RM; Lus, DD; Chu, Y.; Brooks, RM; Zimmerman, KA; El Accaoui, R.; Davis, MK; Hajj, GP; Zimmerman, MB; Heistad, DD Osteoprotegerin inhibits aortic valve calcification thiab khaws cov haujlwm valve hauv cov nas hypercholesterolemic. PLoS IB 2013, 8, e65201. [CrossRef]

15. Morena, M.; Dupuy, AM; Jaussent, ib.; Vernhet, H.; Gahid, G.; Klouche, K.; Bargnoux, AS; Delcourt, C.; Canaud, B.; Cristol, JP Ib qho kev txiav tawm ntawm cov ntshav plasma osteoprotegerin qib tuaj yeem kwv yees qhov pom ntawm cov hlab ntsha coronary calcification hauv cov neeg mob raum mob ntev. Nephrol. Hu rau. Hloov. Xyoo 2009, 24, 3389–3397. [CrossRef]

16. Mikami, S.; Hamano, T.; Fujii, N.; Nagasawa, Y.; Isaka, Y.; Moriyama, T.; Matsuhisa, M.; Ib, T.; Yim, E.; Hori, M. Serum osteoprotegerin ua ib qho kev tshuaj ntsuam xyuas rau cov hlab ntsha coronary calcification qhab nia hauv cov neeg mob ntshav qab zib ua ntej dialysis. Hypertens. Res. 2008, 31, 1163–1170. [CrossRef]

17. Marques, GL; Hayashi, S.; Bjallmark, ib.; Larsson, M.; ib. Riella, M.; Olandoski, M.; Lindholm, IB; Nascimento, MM Osteoprotegerin yog ib qho cim ntawm kev tuag ntawm cov hlab plawv hauv cov neeg mob uas muaj kab mob raum ntev 3-5. Sci. Rep. 2021, 11, 2473. [CrossRef]

18. Huang, QX; Li, JB; Huang, N.; Huang, XWM; Li, YL; Huang, FX Elevated Osteoprotegerin Concentration Predicts nce kev pheej hmoo ntawm cov hlab plawv tuag nyob rau hauv cov neeg mob uas muaj mob raum kab mob: Ib tug Systematic Review thiab Meta-Analysis. Ntshav Qab Zib. Res. Xyoo 2020, 45, 565–575. [CrossRef]

19. Kami 'nska, J.; Stopi 'nski, M.; Mucha, K.; Pac, M.; Goł ˛ebiowski, M.; Niewczas, MA; P ˛aczek, L.; Foroncewicz, B. Circulating Osteoprotegerin nyob rau hauv mob raum mob thiab tag nrho-ua rau tuag. Int. J. Gen. Med. 2021, 14, 2413–2420. [CrossRef]

20. Huang, QX; Li, JB; Huang, XWM; Jiang, LPB; Huang, L.; Ib, HW; Yang, WQ; Paj, J.; Li, YL; Huang, FX Circulating Osteoprotegerin Levels Independently Predict All-cause Mortality in Patients with Chronic Kidney Disease: A Meta-analysis. Int. J. Med. Sci. Xyoo 2019, 16, 1328–1337. [CrossRef]

21. Lin, WC; Tsai, JP; Laj, YH; Lin, YL; Kuo, CH; Wang, CH; Hsu, BG Serum qib osteoprotegerin zoo cuam tshuam nrog cov kab mob peripheral artery nyob rau hauv cov neeg mob nrog peritoneal dialysis. Ren. Ua tsis tiav. 2020, 42, 131–136. [CrossRef]

22. Hou, JS; Lin, YL; Wang, CH; Laj, YH; Kuo, CH; Subeq, YM; Hsu, BG Serum osteoprotegerin yog tus cim kev ywj pheej ntawm cov hlab ntsha hauv nruab nrab raws li kev soj ntsuam siv carotid-femoral pulse yoj tshaj tawm hauv cov neeg mob hemodialysis: Kev tshawb nrhiav ntu ntu. BMC NPE. 2019, 20, 184. [CrossRef]

23. Csiky, B.; Saib, B.; Peti, A.; Lakatos, O.; Prémusz, V.; Sulyok, E. Qhov cuam tshuam ntawm Osteocalcin, Osteoprotegerin, thiab Osteopontin ntawm Arterial Stiffness nyob rau hauv cov neeg mob raum tsis ua hauj lwm ntawm Hemodialysis. Ntshav Qab Zib. Res. 2017, 42, 1312–1321. [CrossRef]

24. Avila, M.; Mora, C.; Prado, MDC; Zavala, M.; Paniagua, R. Osteoprotegerin yog tus kws tshaj lij tshaj lij rau kev nce qib ntawm Arterial Calcification hauv Peritoneal Dialysis Cov Neeg Mob. Am. J. Neeb. 2017, 46, 39–46. [CrossRef]

25. Bargnoux, AS; Dupuy, AM; Garrigue, V.; Deleuze, S.; Cristol, JP; Mourad, G. Kev hloov lub raum txo qis osteoprotegerin qib. Hloov. Proc. 2006, 38, 2317–2318. [CrossRef]

26. Hjelmesaeth, J.; UA, T.; Flyvbjerg, A.; Bollersev, J.; Leivestad, T.; Jensen, T.; Hansen, TK; Thiel, S.; Sagedal, S.; Rauislien, J.; ua al. Thaum ntxov posttransplant serum osteoprotegerin qib kwv yees mus ntev (8- xyoo) tus neeg mob muaj sia nyob thiab mob plawv tuag hauv cov neeg mob hloov lub raum. J. Am. Soc. Nephrol. 2006, 17, 1746–1754. [CrossRef]

27. Aw, KH; Park, SK; Park, HC; Chin, HJ; Chaw, DW; Choi, KH; Han, SH; Yog, TH; Li, K.; Kim, YS; ua al. KNOW-CKD (Korean cohort study for Outcome in Patients With Chronic Kidney Disease): Tsim thiab siv. BMC NPE. 2014, 15, 80. [CrossRef]

28. Levey, AS; Stevens, LA; Schmid, CH. Zhang, YL; Castro, AF, 3rd; Feldman, HI; Kusek, JW; Eggers, P.; Van Lente, F.; Greene, T.; ua al. Ib qho kev sib npaug tshiab los kwv yees glomerular filtration rate. Ann. Intern. Med. 2009, 150, 604–612. [CrossRef] [PubMed]

29. Kim, CS; Bae, EH; Ma, SK; Han, SH; Choi, KH; Li, J.; Chaw, DW; Aw, KH; Aw, C.; Kim, SW; ua al. Lub koom haum ntawm Serum Osteoprotegerin Qib nrog cov pob txha poob hauv cov kab mob hauv lub raum: Kev pom los ntawm KNOW-CKD Txoj Kev Kawm. PLoS ONE 2016, 11, e0166792. [CrossRef] [PubMed]

30. Rymarz, A.; Romejko, K.; Matyjek, A.; Bartoszewicz, Z.; Niemczyk, S. Serum Osteoprotegerin yog ib qho kev ywj pheej ntawm cov teeb meem metabolic nyob rau hauv cov neeg mob uas tsis yog mob ntshav qab zib. Nutrients 2021, 13, 3609. [CrossRef] [PubMed]

31. Del Toro, R.; Cavallari, I.; Tramontana, F.; Park, K.; Strollo, R.; Valente, L.; ib. De Pascalis, M.; Grigioni, F.; Pozzilli, P.; Buzzetti, R. ua al. Kev koom tes ntawm cov pob txha biomarkers nrog cov kab mob atherosclerotic siab heev hauv cov neeg uas rog dhau / rog. Endocrine 2021, 73, 339–346. [CrossRef]

32. Alves-Lopes, R.; Neeb, KB; Strembitska, UA; Harvey, AP; Harvey, KY; Yusuf, H.; Haniford, S.; ib. Hepburn, RT; Deej, J.; Beatti, W. ua al. Osteoprotegerin tswj hwm vascular kev ua haujlwm los ntawm syndecan-1 thiab NADPH oxidase-derived reactive oxygen hom. Clin. Sci. 2021, 135, 2429–2444. [CrossRef]

33. Bucay, N.; Sarosi, ib.; Dunstan, CR; Morony, S.; Tarpley, J.; Capparelli, C.; Scully, S.; Tan, HL; Xu, W. Lacey, DL; ua al. osteoprotegerin-tsis muaj nas nas tsim ntxov osteoporosis thiab arterial calcification. Genes Dev. 1998, 12, 1260–1268. [CrossRef]

34. Chae, SY; Chung, W.; Kim, YH; Aw, YK; Li, J.; Choi, KH; Aw, C.; Kim, YS Qhov Kev Sib Raug Zoo ntawm Cov Ntshav Osteoprotegerin nrog Cov Txheej Txheem Tsis Zoo Ntawm Cov Kab Mob Ntshav Qab Zib thiab Arterial Stiffness nyob rau hauv cov neeg mob uas muaj Pre-Dialysis Chronic raum Kab Mob: Cov txiaj ntsig tau los ntawm KNOW-CKD Txoj Kev Kawm. J. Korean. Med. Sci. Xyoo 2018, 33, e322. [CrossRef]

35. Sigrist, MK; Levin, UA; Ib, L.; McIntyre, CW Elevated osteoprotegerin yog txuam nrog tag nrho cov neeg tuag nyob rau hauv CKD theem 4 thiab 5 cov neeg mob ntxiv rau vascular calcification. Nephrol. Hu rau. Hloov. 2009, 24, 3157–3162. [CrossRef]

36. Boardman, H.; Lewandowski, AJ; Lazdam, M.; Kenworthy, Y.; Whitworth, P.; Zwager, CL; Francis, JM; Yog, CY; Williamson, W. Neubauer, S.; ua al. Aortic stiffness thiab ntshav siab variability nyob rau hauv cov tub ntxhais hluas: ib tug multimodality kev tshawb fawb ntawm central thiab peripheral vasculature. J. Hypertens. 2017, 35, 513–522. [CrossRef]

37. Hoshide, S. Clinical implication of visit-to-visit blood pressure variability. Hypertens. Res. Xyoo 2018, 41, 993–999. [CrossRef]

38. Mena, L.; Pintos, S.; Queipo, NV; Aizpúrua, JA; Mastre, G.; Sulbarán, T. Ib qho kev ntsuas txhim khu kev qha rau qhov tseem ceeb ntawm cov ntshav siab hloov pauv. J. Hypertens. 2005, 23, 505–511. [CrossRef]

39. Rothwell, PM; Howard, SC; Dolan, E.; O'Brien, E.; Dobson, EJ; Dahlöf, IB; Sever, PS; Poulter, NR Prognostic qhov tseem ceeb ntawm kev mus ntsib-mus-mus txawv tebchaws, siab tshaj plaws systolic ntshav siab, thiab episodic hypertension. Lancet 2010, 375, 895–905. [CrossRef]

【Yog xav paub ntxiv: david.deng@wecistanche.com / WhatApp:86 13632399501 】