【關(guān)鍵詞】高血壓;腎功能不全,慢性;糖代謝異常;脂質(zhì)蓄積指數(shù);隊(duì)列研究 【中圖分類號】R544.1 R692.5【文獻(xiàn)標(biāo)識碼】A DOI:10.12114/j.issn.1007-9572.2024.0304
Associationof Lipid Accumulation Product Index and Chronic Kidney Disease in Patients with Hypertension with Abnormal Glucose Metabolism:a Retrospective Cohort Study
ZHANG Xin ZHUQing LINanfang
1.Department ofGraduate,XinjiangMedical University,Urumqi83oooo,China
2.Hypertension CenterofPeople's HospitalofXinjiang Uygur AutonomousRegion/Xinjiang HypertensionInstitute/NHCKey LaboratoryofHypertensionClinical Research/KeyLaboratoryofXinjiang UygurAutonomous Region \"HypertensionResearch Laboratory\"Xinjiang ClinicalMedicalResearch CenterforHypertension(Cardio-Cerebrovascular)Diseases,Urumqi830000, China
Corresponding author:LI Nanfang,Chief physician/Doctoral supervisor;E-mail:lnanfang2O16@sina.com
【Abstract】BackgroundThe incidence and prevalence of chronic kidney disease(CKD)remain high.Hypertension anddiabetesfrequentlycoexistandjointlyacceleratetheprogresionofidneydisease.Thelipidaccmulationproductindex"(LAPI)isanovelindicatorforpredictingcardiovasculardiseaseandabnormalitiesinglucosemetabolism,anditsrelationship with CKD warants further investigation.ObjectiveThis studyaimed to investigate therelationship betweenLAPIand the risk of developing CKD in patients with hypertension and abnormal glucose metabolism.MethodsAretrospectivecohortof 2033 patients withhypertensionandabnormal glucose metabolismadmited totheHypertensionCenterof People'sHospitalof Xinjiang UygurAutonomousRegionfromJanuary2O12toMay2O19 was enrolled.Generalpatientinformationandlaboratorytest indicators werecolected.TheLAPIwas calculated,andthe populationwas dividedintofour groupsbasedonLAPIquartiles:Q1 ( LAPI?44.03 , n=509 ),Q2 ( 44.0398.90, (204號 n=508 ).Patients were followedup,with the endpoint event being CKD.Kaplan-Meier curves were used to analyze the cumulative incidenceofCKDat diffrentLAPIlevels,andthe Log-rank test was used tocompare differences.Multivariate Coxregresson models were employed toanalyze the relationship betweenLAPIand CKD.Restricted cubic splines were fitted tothe multivariate Coxregresion model toexplore the dose-response relationship betweenLAPIand CKD.Subgroupanalysis andsensitivityanalysis were conducted to testthe stabilityof the relationship between LAPIand CKD.ResultsSignificant diffrences were observed in age,gender,BMI,waist circumference,heartrate,diastolic blood pressre,smoking, alcoholconsumption,uricacid,totalcholesterol,triglycerides,high-densitylipoprotein,low-densitylipoprotein,glycated hemoglobin,fasting blood glucose,use ofcalciumchannel blockers,and hypoglycemic treatment among the4 groups ( Plt;0.05 ). Log-rank test results indicated that the cumulative risk of CKD increased with elevating LAPI levels( χ2=14.48 , Plt;0.001 ). Multivariate Cox regresson analysis revealed thatfor each standard deviation increase in LAPI,the hazard ratio ( HR ) for CKD increased by 12.5%(HR=1.125,95%CI=1.035-1.223, P =0.005);compared to the Q1 group,the Q4 group had a 54.9% (204號 higher risk of CKD(HR=1.549,95%CI=1.129-2.125, P =0.007).Restricted cubic spline regression analysis showed that LAPIgt;65.59 was a risk factor for CKD( P =0.007). Interaction and subgroup analyses revealed that the association between LAPI andthe risk of developing CKDremained stable.ConclusionIn patients with hypertensionandabnormal glucose metabolism,a higherLAPI in the early stages increases the riskof developing CKD.
【Key words】Hypertension;Renal insufficiency,chronic;Abnormal glucose metabolism;Lipid accumulation product index;Cohort study
慢性腎臟?。╟hronic kidneydisease,CKD)是一種腎臟慢性進(jìn)展性疾病,發(fā)病常與高血壓、糖尿病等有關(guān)[1-3]。CKD在全球普遍流行,CKD在中國和美國的患病率分別達(dá)到了 8.2%[4-5] 和 10%[6] ;CKD在高血壓患者和糖尿病患者中的患病率分別為 27.6% 、 。較高的患病率使CKD 成為了一個(gè)迫切需要解決的公共衛(wèi)生問題,尤其在高血壓和糖尿病患者中更值得關(guān)注。高血壓患者常伴有血脂異常、血糖異常、胰島素抵抗、炎癥等代謝紊亂[8]。臨床中為了早期發(fā)現(xiàn)和控制這些變化常計(jì)算一些指標(biāo),如脂質(zhì)蓄積指數(shù)(lipidaccumulationproductindex,LAPI),這對于預(yù)防CKD的發(fā)生和發(fā)展具有重要意義。
LAPI是結(jié)合腰圍和三酰甘油的代謝指數(shù),是中心脂質(zhì)累積的標(biāo)志物[9]?;A(chǔ)研究表明[10],腎臟細(xì)胞中脂質(zhì)累積和沉淀會(huì)加劇腎臟損傷,脂質(zhì)代謝和腎功能之間存在著潛在的病理生理聯(lián)系[1];血脂異常與腎小球硬化和腎小管纖維化的機(jī)制相關(guān)[12-13];據(jù)此,LAPI很可能作為檢測早期腎損傷的替代標(biāo)志物。近年來,LAPI在高血壓等心血管疾病和糖尿病及其并發(fā)癥中受到廣泛關(guān)注。觀察性研究表明[14-17],LAPI是識別和預(yù)測心血管疾病的新指標(biāo),也與糖尿病等疾病的腎臟損害結(jié)局有關(guān)。高血壓、高血糖、胰島素抵抗和脂質(zhì)紊亂之間的復(fù)雜關(guān)系進(jìn)一步加速CKD的發(fā)展[18]。為了明確LAPI在CKD發(fā)展進(jìn)程中發(fā)揮著推動(dòng)作用,很有必要在普通或特殊人群中,尤其是高血壓和糖代謝異常的患者中,去研究LAPI與CKD之間的關(guān)系。
因此,本研究旨在高血壓伴糖代謝異?;颊咧刑接慙API與CKD發(fā)生風(fēng)險(xiǎn)的關(guān)系,希望通過這項(xiàng)回顧性隊(duì)列研究揭示LAPI在這類患者中的臨床意義,為高血壓合并糖代謝異?;颊叩脑缙谧R別和干預(yù)提供新的理論依據(jù)和臨床指導(dǎo)。
1對象與方法
1.1 研究對象
本研究為回顧性隊(duì)列研究。研究納入2012年1月—2019年5月收治于新疆維吾爾自治區(qū)人民醫(yī)院高血壓中心的高血壓伴糖代謝異?;颊邽檠芯繉ο?。1.1.1納入標(biāo)準(zhǔn):(1)符合高血壓診斷的住院患者;(2)同時(shí)符合糖代謝異常的住院患者;(3)年齡 gt;18 歲。1.1.2排除標(biāo)準(zhǔn):(1)繼發(fā)性高血壓;(2)既往3個(gè)月內(nèi)發(fā)生過不良心血管事件;(3)患有惡性腫瘤;(4)基線腎功能不全;(5)一過性蛋白尿和一過性腎功能損傷者,如感染、結(jié)石等;(6)基線體格檢查和生化指標(biāo)資料不全;(7)失訪。最終納入2033例患者。
本研究遵循《赫爾辛基宣言》原則。研究經(jīng)新疆維吾爾自治區(qū)人民醫(yī)院倫理委員會(huì)批準(zhǔn)(批準(zhǔn)號:KY2024060801),免除知情同意。
1.2 研究方法
1.2.1流行病學(xué)收集的指標(biāo):流行病學(xué)收集的指標(biāo)包括一般資料,如性別、年齡、BMI、腰圍、心率、收縮壓、舒張壓、吸煙、飲酒,實(shí)驗(yàn)室檢查指標(biāo)包括估計(jì)腎小球?yàn)V過率、尿酸、肌酐、總膽固醇、三酰甘油、高密度脂蛋白、低密度脂蛋白、糖化血紅蛋白、空腹血糖以及用藥情況。吸煙定義為每天吸煙1支及以上,連續(xù)或累計(jì)6個(gè)月[19-20]。飲酒指研究開始前1年內(nèi)每周飲酒 ?1 次[19-20]
1.2.2疾病的定義:高血壓定義為收縮壓 ?140mmHg ( 1mmHg=0.133kPa )和 1 或舒張壓 ?90mmHg ,或正在接受降壓治療[19-21]。糖代謝異常定義為空腹血糖和糖化血紅蛋白檢測結(jié)果提示糖尿病前期和糖尿病;糖尿病定義為先前的明確診斷或使用抗糖尿病藥物,或餐后2h 血糖 ?11.1mmol/L ,或空腹血糖 ?7.0mmol/L ;糖尿病前期是葡萄糖失調(diào)的中間階段,定義為 75g 口服葡萄糖耐量試驗(yàn)期間,空腹血糖 100mg/dL ( 5.6mmol/L )~125mg/dL ( 6.9mmol/L ),糖化血紅蛋白 5.7%~6.4% ,或 2h 血糖 140mg/dL ( 7.8mmol/L ) ~199mg/dL (11.0mmol/L)[19-20,22]
1.2.3LAPI計(jì)算:根據(jù)收集的數(shù)據(jù)計(jì)算LAPI。LAPI(男)Σ=Σ [腰圍( cm )-65] × 三酰甘油( mmol/L ),LAPI(女)Σ=Σ [腰圍( cm ) -58 】 × 三酰甘油(mmol/L)。
1.2.4分組:按LAPI四分位數(shù)將人群資料分為四組,Q1組( LAPI?44.03,n=509 ),Q2組( 44.0398.90 ! n=508 )。
1.2.5隨訪和終點(diǎn)事件:以2012年1月健康檢查或再住院為隨訪起始時(shí)間,如研究對象未發(fā)生終點(diǎn)事件,隨訪截止時(shí)間為2021-12-31;如研究對象未發(fā)生終點(diǎn)事件而中途死亡,隨訪截止時(shí)間為死亡時(shí)間。隨訪資料通過門診或再住院的隨訪記錄或體檢資料獲取。隨訪終點(diǎn)事件為CKD。為了明確CKD的診斷,本研究在電子病歷系統(tǒng)中提取了再入院患者的出院診斷,排除一過性蛋白尿、一過性腎功能不全以及隨訪時(shí)間 lt;3 個(gè)月的患者。失訪定義為患者出院后無隨訪記錄與年度健康檢查數(shù)據(jù)。
1.2.6終點(diǎn)事件的定義:CKD定義為至少持續(xù)3個(gè)月出現(xiàn)估計(jì)腎小球?yàn)V過率(eGFR) lt;60mL?min-1 ·(1.73m2 )-和/或在使用尿試紙的定性尿蛋白檢測中存在陽性蛋白尿( ?1+ )以及尿白蛋白與肌酐比值 ≥30mg/g[23] 。
1.3 統(tǒng)計(jì)學(xué)方法
采用 IBM SPSS Statistics R23.0.0.0、R4.3.2和
GraphPadPrism9.5.1.733統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析。計(jì)量資料以! )表示,多組間比較采用單因素方差分析。計(jì)數(shù)資料采用例( (% )表示,組間比較采用 χ2 檢驗(yàn)。采用多重共線性分析,排除多重共線性問題。采用Kaplan-Meier曲線分析不同LAPI水平的CKD的累積發(fā)生率,并采用Log-rank檢驗(yàn)比較差異。多因素 Cox 回歸模型分析LAPI與CKD的關(guān)系。采用限制性立方樣條曲線擬合多因素 Cox 回歸模型探索的LAPI與CKD的效應(yīng)關(guān)系。采用亞組分析和敏感性分析檢驗(yàn)LAPI與CKD關(guān)系的穩(wěn)定性,以 Plt;0.05 為差異有統(tǒng)計(jì)學(xué)意義。
2結(jié)果
2.1基線資料
共納入了2033例高血壓伴糖代謝異?;颊?,女884例、男1149例,平均年齡( 55.5±11.1 )歲,中位隨訪時(shí)間2.9(1.5,4.2)年。4組年齡、性別、BMI、腰圍、心率、舒張壓、吸煙、飲酒、尿酸、總膽固醇、三酰甘油、高密度脂蛋白、低密度脂蛋白、糖化血紅蛋白、空腹血糖、服用鈣離子拮抗劑、降糖藥比較,差異有統(tǒng)計(jì)學(xué)意義( Plt;0.05 );各組收縮壓、eGFR、肌酐、服用血管緊張素轉(zhuǎn)化酶抑制劑和血管緊張素受體拮抗劑、服用 β 受體阻滯劑和利尿劑比較,差異無統(tǒng)計(jì)學(xué)意義( Pgt;0.05 ),見表1。
2.2LAPI分組與CKD的累積風(fēng)險(xiǎn)情況
Log-rank檢驗(yàn)結(jié)果顯示,隨著LAP水平升高,Q1~Q4組CKD累積風(fēng)險(xiǎn)升高,差異有統(tǒng)計(jì)學(xué)意義( x2=14.48 , Plt;0.001 ),見圖1。
2.3基線指標(biāo)的共線性分析
將基線指標(biāo)進(jìn)行了共線性診斷分析,當(dāng)排除方差膨脹系數(shù) gt;10 的指標(biāo)后,其余指標(biāo)的方差膨脹因子 lt;6 排除共線性,見表2。
2.4多因素Cox回歸分析探討LAPI與CKD的相關(guān)性
以患者是否發(fā)生CKD為因變量(賦值:否 =0 ,是-1 ),以LAPI(賦值為實(shí)測值)、LAPI每增加一個(gè)標(biāo)準(zhǔn)差(賦值:實(shí)測值的標(biāo)準(zhǔn)化 Z 值)、LAPI分組(賦值:Q1組 =1 ,Q2組 =2 ,Q3組 =3 ,Q4組 =4 )為自變量,探討LAPI對CKD的影響作用,結(jié)果顯示在模型4中,LAPI每增加1個(gè)標(biāo)準(zhǔn)差,CKD的風(fēng)險(xiǎn)比例升高 12.5% ( HR=1.125 , 95%CI=1.035~1.223 , P=0.005 );Q4組較Q1組CKD的風(fēng)險(xiǎn)比例升高了 54.9% ( HR=1.549 ,95%CI=1.129~2.125 , P=0.007 ),見表3。
2.5LAPI與 CKD 的限制性樣條回歸曲線
以CKD為因變量,LAPI為自變量繪制了限制性樣條回歸曲線,結(jié)果顯示, LAPIgt;65.59 時(shí)為CKD的危險(xiǎn)因素( P=0.007 ),見圖2。
2.6LAPI與 CKD 的亞組分析
以CKD為因變量(賦值:否 =0 ,是 =1 ),以年齡(賦值: ?60 歲 =0 gt;60 歲 =1 )、性別(賦值:男 =1 ,女 =2 )、BMI(賦值: ?28kg/m2=0 , gt;28kg/m2=1 )、吸煙(賦值:
?90mmHg=0 , )的分組為自變量進(jìn)行了交互分析和亞組分析,結(jié)果顯示吸煙和LAPI存在交互作用( P☉lt;0.05 ),年齡、性別、BMI、飲酒、收縮壓、
舒張壓之間不存在交互作用( ),見圖3。
3討論
本研究結(jié)果顯示,LAPI越大,高血壓合并糖代謝異常的患者發(fā)生CKD的累積風(fēng)險(xiǎn)越高。在多因素Cox回歸模型中,調(diào)整了年齡、性別、BMI、收縮壓、舒張壓、心率、吸煙、飲酒、糖化血紅蛋白、血肌酐后,當(dāng) LAPIgt;98.90 時(shí),CKD風(fēng)險(xiǎn)比例為1.549( 95%CI=1.129~2.125 , ),相較于 LAPIlt;44.03 時(shí)的CKD風(fēng)險(xiǎn)增加了 54.9% 。在限制性樣條回歸曲線中,同樣調(diào)整了這些混雜變量后,若 LAPIgt;65.59 ,則CKD的風(fēng)險(xiǎn)比例顯示大于1,并且LAPI的增加與CKD風(fēng)險(xiǎn)的增加呈平穩(wěn)的正相關(guān)。這些結(jié)果表明LAPI與高血壓伴糖代謝異?;颊叩腃KD發(fā)生密切相關(guān),并且在高血壓和糖代謝異常共存的疾病中,LAPI為CKD的獨(dú)立危險(xiǎn)因素。
LAPI反映了體脂蓄積過度,是許多慢性代謝疾病的靶器官損害的指標(biāo)[24],是代謝綜合征的可靠指標(biāo)[25-26]、心血管風(fēng)險(xiǎn)相關(guān)指標(biāo)[27],還與2型糖尿病發(fā)生風(fēng)險(xiǎn)[28-30]、高血壓動(dòng)脈硬化[31]以及腎臟損傷等相關(guān)。既往觀察性研究顯示,200例高血壓或糖尿病患者中CKD 組的LAPI較非CKD 組高[32],931例2型糖尿病患者中糖尿病腎病組的LAPI高于非糖尿病腎病組[33],在1960例參與者的研究中使用LAPI預(yù)測了高血壓的風(fēng)險(xiǎn)情況[34],這些研究僅對某一時(shí)間點(diǎn)CKD患者的LAPI進(jìn)行了監(jiān)測和評估,或者僅使用了LAPI預(yù)測高血壓等單一疾病的風(fēng)險(xiǎn),還不能充分說明在高血壓和糖代謝異常共存的復(fù)雜情況下LAPI是否對其并發(fā)CKD風(fēng)險(xiǎn)的預(yù)測情況。本研究結(jié)果為這些既往觀察性研究提供了更多補(bǔ)充,再次驗(yàn)證了LAPI與CKD的關(guān)系。
本研究通過回顧性隊(duì)列研究,發(fā)現(xiàn)了LAPI與CKD的累積風(fēng)險(xiǎn)呈正相關(guān)。研究結(jié)果既是對過往研究的補(bǔ)充,也為高血壓伴糖代謝異常人群中CKD找到了一個(gè)LAPI
的風(fēng)險(xiǎn)預(yù)測值,為臨床疾病的診斷提供了潛在價(jià)值,為高血壓和糖代謝異常患者的臨床檢測提供了參考指標(biāo)。未來的研究中,需要更多臨床醫(yī)生和科研學(xué)者關(guān)注到脂質(zhì)代謝與腎臟損傷的內(nèi)在關(guān)系,需要開展更多基礎(chǔ)研究探討相關(guān)的病理生理機(jī)制,需要開展臨床隨機(jī)對照試驗(yàn)去充分證明LAPI與CKD的關(guān)系,從而找到一個(gè)合理干預(yù)疾病進(jìn)展的方式,對人類生命健康保駕護(hù)航。
本研究是一項(xiàng)大樣本的回顧性隊(duì)列研究,相較于既往研究,提供了更加可行的科學(xué)證據(jù)。但本研究存在以下局限性:首先,本研究人群僅為我國新疆地區(qū)高血壓合并糖代謝異常患者,研究結(jié)果不一定具有推廣性。其次,本研究在分析過程中對混雜因素進(jìn)行了調(diào)整,但仍不能排除被測量或未記錄的混雜變量。
總之,本研究結(jié)果表明,LAPI與CKD的累積風(fēng)險(xiǎn)呈正相關(guān),尤其是在高血壓合并糖代謝異常的患者中。在調(diào)整了混雜變量后,高水平LAPI組的CKD發(fā)生風(fēng)險(xiǎn)顯著高于低水平LAPI組。合理的控制LAPI或許能有效預(yù)防和管理高血壓合并糖代謝異常患者腎臟損害的發(fā)生,對患者CKD的防治具有重大而深遠(yuǎn)的意義。
作者貢獻(xiàn):張欣負(fù)責(zé)數(shù)據(jù)的統(tǒng)計(jì)分析、圖表制作、論文撰寫;朱晴負(fù)責(zé)數(shù)據(jù)收集和文章質(zhì)量控制;李南方提出了研究思路和研究設(shè)計(jì)方案,對文章整體負(fù)責(zé)并監(jiān)督管理。
本文無利益沖突。
張欣D https://orcid.org/0009-0004-2697-4548
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(收稿日期:2024-08-01;修回日期:2024-12-16)