陳關芬　辛麗芹　楊麗華

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腹透患者心血管鈣化的發(fā)生率、分布特點及相關影響因素

陳關芬辛麗芹楊麗華

目的通過對腹膜透析患者的心臟瓣膜鈣化及主動脈弓鈣化進行評價，分析心血管鈣化的發(fā)生率、分布特點及相關影響因素。方法選取174例腹膜透析患者，分別于統(tǒng)一時間段測量肢肱動脈血壓，分別記錄患者的血尿素氮、肌酐值；24 h的尿量、透出液量、尿素氮、肌酐值及透出液尿素氮、肌酐濃度值；并通過上述測定值計算評估透析充分性和殘余腎功能。每隔6個月測定患者的生化指標。對腹膜透析患者心臟進行多普勒超聲檢查和患者胸部X線片檢查，用Logistics回歸分析評判心血管鈣化危險因素。結果主動脈弓鈣化及瓣膜鈣化類別中鈣化患者的年齡、透析齡及血磷值均高于非鈣化患者(P<0.05)；鈣化患者的殘余腎功能值顯著低于非鈣化患者(P<0.05)；隨著年齡/透析齡的增加，瓣膜/主動脈弓鈣化的發(fā)生率顯著上升(P<0.05)。年齡、透析齡和鈣磷乘積均是影響心臟瓣膜鈣化的獨立危險因素(P<0.05)，其中鈣磷乘積危險系數(shù)最高；年齡、透析齡和血磷是影響主動脈弓鈣化的獨立危險因素(P<0.05)，其中血磷危險系數(shù)最高；殘余腎功能是能影響心臟瓣膜/主動脈弓鈣化的獨立因素(P<0.05)，而且是保護因素。結論年齡和透析齡是影響心臟瓣膜鈣化及主動脈弓鈣化的獨立危險因素，鈣磷乘積是影響心臟瓣膜鈣化危險系數(shù)最高的獨立因素，血磷是影響主動脈弓鈣化危險系數(shù)最高的獨立因素。

腹膜透析患者；心臟瓣膜鈣化；主動脈弓鈣化；心血管鈣化

腹膜透析作為終末期腎病替代治療方式之一，可有效延長病患的生存時間，與血液透析相比，臨床更能保持腎功能衰竭患者的心血管穩(wěn)定性及保護殘余腎功能(residual renal function, RRF)，且腹透所需設備簡單，操作便易，更適于家庭透析使用[1-4]。隨著腹透技術的廣泛應用，其帶來的并發(fā)癥也引起了醫(yī)療工作者的關注。Remón-Rodríguez等[5]發(fā)現(xiàn)腹透的主要并發(fā)癥是心血管疾病(cardiovascular disease, CVD)，發(fā)病率大于30%。CVD是慢性腎臟疾病(chronic kidney diseases, CKD)患者常見并發(fā)癥，而心血管鈣化是慢性腎臟疾病患者CVD的主要原因之一[6-8]。在正常的機體條件下，鈣化是對礦物質化進行及誘導的精控步驟，不會產(chǎn)生血管鈣化[9]。但是當機體發(fā)生某處病變時，鈣化就會成為不可控的，一般認為血管粥樣硬化及年齡對血管鈣化起著正調控的作用[10]。然而具體是什么因素影響著終末期腎功能衰竭患者的心血管鈣化，尚不完全清楚。因此本研究以腹透患者為研究對象，分別以心超檢測心臟瓣膜，胸部X線檢測和評估主動脈弓鈣化清況，探討腹膜透析患者心血管鈣化的發(fā)生率及影響因素分析，以期對臨床有一定的理論指導。

1　資料與方法

1.1一般資料選取2012年6月至2015年6月在云南省曲靖市第二人民醫(yī)院和昆明醫(yī)科大學第二附屬醫(yī)院腹膜透析治療中心進行腹透的患者174例，其中男104例，女70例；平均年齡(63±14)歲；平均BMI(23.4±2.4)kg/m2；透析齡6～93個月，平均透析19個月；收縮壓(145±12)mm Hg；舒張壓(79±10)mm Hg；平均動脈壓(101±8)mm Hg；殘余腎功能(5.3±4.2)ml/min；腹膜Kt/V(3.5±2.6)；殘腎Kt/V(2.0±1.9)；腹膜Ccr(48±26)L/周；殘腎Ccr(29±19)L/周；iPTH(2.37±2.48)pg/ml；校正鈣(2.55±0.26)mmol/L；血磷(1.7±0.4)mmol/L；血紅蛋白(102±18)g/L；血糖(6.5±2.1)mmol/L；TG(2.0±1.2)mmol/L；TC(4.8±0.9)mmol/L；LDL(2.7±0.8)mmol/L；HDL(1.0±0.3)mmol/L。透析齡>12個月，患者年齡>18歲；排除外傷、創(chuàng)傷及嚴重感染患者，長期服用糖皮質激素，合并甲亢性心臟病及惡性骨腫瘤疾病等。研究方案經(jīng)云南省曲靖市第二人民醫(yī)院倫理委員會批準，進行的所有研究內容均知會受試人員并簽署知情同意書。

1.2方法患者分別于統(tǒng)一時間段測量肢肱動脈血壓3次，并求取平均動脈壓。分別記錄患者的血尿素氮、肌酐值；24 h的尿量、透出液量、尿素氮、肌酐值及透出液尿素氮、肌酐濃度值；并通過上述測定值計算評估透析充分性和殘余腎功能。每隔6個月測定患者的生化指標[iPTH、校正鈣、血磷、血紅蛋白、血糖、三酰甘油(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、膽固醇(TC)]，共計3次測量數(shù)據(jù)。對腹膜透析患者心臟進行多普勒超聲檢查，瓣膜鈣化指主動脈瓣或二尖瓣有一個或多個瓣葉上有1 mm以上的強回聲區(qū)。對腹膜透析患者胸部進行X線片檢查，主動脈弓鈣化有4個等級：0級(未見瓣膜鈣化)、1級(鈣化區(qū)域呈點狀或薄片狀)、2級(一個及以上區(qū)域的鈣化增厚增密)和3級(鈣化呈圓周樣)。

2　結果

2.1所選腹膜透析患者的一般情況分析比較174例中，男104例(59.77%)；平均年齡(63±14)歲；主動脈弓鈣化及瓣膜鈣化類別中鈣化患者的年齡、透析齡及血磷值均顯著高于非鈣化患者(P<0.05)；鈣化患者的殘余腎功能值顯著低于非鈣化患者(P<0.05)；體重指數(shù)(BMI)、收縮壓、舒張壓、平均動脈壓、腹膜Kt/V、殘腎Kt/V、腹膜肌酐清除率(creatinine clearance rate,Ccr)、殘腎Ccr、全段甲狀旁腺激素(intact parathyroid hormone, iPTH)、校正鈣、血紅蛋白、血糖、TG、TC、LDL及HDL在鈣化及非鈣化患者差異無統(tǒng)計學意義(P>0.05)。見表1。

2.2腹膜透析患者主動脈弓/瓣膜鈣化情況分析主動脈弓/瓣膜鈣化類別中鈣化組與非鈣化組中年齡及透析齡存在差異性，因此根據(jù)不同的年齡/透析齡把瓣膜/主動脈弓鈣化患者分別分為3組，并比較鈣化發(fā)生率。隨著年齡/透析齡的增加，瓣膜/主動脈弓鈣化的發(fā)生率顯著上升。見表2、3，圖1、2。

2.3腹膜透析患者主動脈弓/瓣膜鈣化危險因素分析年齡、透析齡和鈣磷乘積均是影響心臟瓣膜鈣化的獨立危險因素，其中鈣磷乘積危險系數(shù)最高，而血磷被排除；年齡、透析齡和血磷是影響主動脈弓鈣化的獨立危險因素，其中血磷危險系數(shù)最高，鈣磷乘積不是影響主動脈弓鈣化的獨立因素；殘余腎功是能影響心臟瓣膜/主動脈弓鈣化的獨立因素，而且是保護因素。見表4、5。

3　討論

心血管疾病是慢性腎臟疾病患者常見并發(fā)癥，而心血管鈣化則是主要原因之一。Ogawa等[11]研究發(fā)現(xiàn)維持性血液透析患者中50.60%存在主動脈弓鈣化；Inoue等[12]的研究結果類似，主動脈弓鈣化發(fā)生率為54.30%；Choi等[13]研究發(fā)現(xiàn)終末期腎病患者血液透析后，有29.90%的患者發(fā)生心臟瓣膜鈣化；Takahashi等[14]研究發(fā)現(xiàn)，有57.50%的血液透析患者發(fā)生心臟瓣膜鈣化。本研究對象為腹膜透析患者，心臟瓣膜鈣化及主動脈弓鈣化發(fā)生率均低于文獻中的血液透析患者；可能與血液透析患者的血流量較高有關，血液動力學不穩(wěn)定，從而易對血管壁造成沖擊力，最終損傷血管內皮細胞。

表1　所選腹膜透析患者的一般情況分析　±s

注：與無鈣化患者比較，*P<0.01

表2　不同年齡患者的心臟瓣膜/主動脈弓鈣化發(fā)生率比較　例(%)

注：與≤45歲比較，*P<0.05；與45～65歲比較，#P<0.05

表3　不同透析齡患者的心臟瓣膜/主動脈弓鈣化發(fā)生率比較　%

表4　心臟瓣膜鈣化危險因素

圖1　不同透析齡/年齡心臟瓣膜鈣化情況

注：≥37月vs≤12月，OR=17.834，P=0.000；≥37月vs≤13～36月，OR=4.412，P=0.000；≥66歲vs≤45歲，OR=7.511，P=0.004；≥66歲vs≤46～65歲，OR=2.895，P=0.004

圖2　不同透析齡/年齡主動脈弓鈣化情況

注：≥37月vs≤12月，OR=12.534，P=0.000；≥37月vs≤13～36月，OR=4.098，P=0.001；≥66歲vs≤45歲，OR=7.102，P=0.002；≥66歲vs≤46～65歲，OR=2.624，P=0.005

表5　主動脈弓鈣化危險因素

Panuccio等[15]的研究結果表明，透析患者中心臟瓣膜鈣化者的透析齡及年齡均顯著高于心臟瓣膜無鈣化者；Avila-Díaz等[16]的研究結果表明，腹透患者中的心臟瓣膜鈣化進展較快者，年齡更高。在本研究中，Logistics回歸分析表明年齡和透析齡是影響心臟瓣膜鈣化及主動脈弓鈣化的獨立危險因素；而且心臟瓣膜鈣化及主動脈弓鈣化在不同的年齡和透析齡中表現(xiàn)出顯著的差異性。年齡≥66歲心臟瓣膜鈣化及主動脈弓鈣化的發(fā)生率分別是小于45歲人群的4.77倍和3.93倍；透析時間大于37月心臟瓣膜鈣化及主動脈弓鈣化的發(fā)生率分別是透析時間小于12月人群的7.72 倍和4.41倍。

體外數(shù)據(jù)研究發(fā)現(xiàn)，在高濃度磷的誘導作用下，血管平滑肌細胞會逐漸向成骨軟骨細胞轉化[17, 18]；Chen等[19]的研究數(shù)據(jù)表明，用尿毒癥病人含磷的血清與血管平滑肌細胞在體外共培養(yǎng)，可使細胞鈣化；Reynolds等[20]認為血鈣和血磷在血管鈣化中起協(xié)同作用；Shroff等[21]的研究表明在相同的鈣磷乘積下，高磷的誘導血管平滑肌細胞鈣化的效率要低于高鈣。臨床研究也證明終末端腎病患者鈣磷發(fā)生與心血管鈣化有顯著的相關發(fā)生。在本研究中，Logistics回歸分析表明除年齡和透析齡，鈣磷乘積是影響心臟瓣膜鈣化危險系數(shù)最高的獨立因素，血磷是影響主動脈弓鈣化危險系數(shù)最高的獨立因素。因此在腎衰病人腹膜透析過程中，要注重防治高磷血和高鈣血的發(fā)生，限制磷和鈣的攝入，并盡量減少鈣磷結合劑的使用。

綜上所述，本研究通過對腹膜透析患者的一般情況、主動脈弓鈣化、瓣膜鈣化情況及相關危險因素進行分析，揭示了年齡和透析齡是影響心臟瓣膜鈣化及主動脈弓鈣化的獨立危險因素，鈣磷乘積是影響心臟瓣膜鈣化危險系數(shù)最高的獨立因素，血磷是影響主動脈弓鈣化危險系數(shù)最高的獨立因素。

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The incidence rate,distribution characteristics and related influencing factors of cadiovascular calcification in peritoneal dialysis patients

CHENGuanfen*,XINLiqin*,YANGLihua.

*DepartmentofNephropathy,TheSecondPeople’sHospitalofQujingCity,Yunnan,Qujing655000,China

ObjectiveTo evaluate the cardiac valve calcification and aortic arch calcification in peritoneal dialysis patients, and to analyze the incidence rate,distribution characteristics and related influencing factors of cadiovascular calcification.MethodsOne hundred and seventy-four patients who underwent peritoneal dialysis in our hospital were enrolled in the study. The patient’s blood pressure of brachial artery was measured in unification time point,and blood urea nitrogen,creatinine values, 24-hour urine volume,dialysis liquid volume,urea nitrogen,creatinine and contents of urea nitrogen and creatinine in dialysis liquid were detected to evaluate the dialysis efficiency and residual renal function of patients. The biochemical indicators of patients were detected at an interval of 6 months,moreover, the patients received Doppler ultrasonography and chest X-ray examination,finally, the risk factors influencing cardiovascular calcification were evaluated by Logistics regression.ResultsThe average age [(63±14)years],dialysis duration and serum levels of phosphorus in patients with aortic arch calcification and heart valve calcification were significantly higher than those of patients without calcification (P<0.05), and residual renal function values were significantly lower than those of of patients without calcification (P<0.05). The incidence of cardiac valve calcification and aortic arch calcification was significantly increased along with the growth of patient’s age and dialysis duration (P<0.05). The patient's age, dialysis duration and calcium-phosphorus product were independent risk factors influencing cardiac valve calcification (P<0.05),in which, the danger coefficient of calcium-phosphorus product was the highest,moreover, patient’s age,dialysis duration and serum levels of phosphorus were independent risk factors influencing aortic arch calcification (P<0.05),in which, the danger coefficient of serum levels of phosphorus was the highest (P<0.05).Besides residual renal function of patients was independent risk factors influencing cardiac valve calcification and aortic arch calcification,furthermore,which was protection factor.ConclusionThe patient’s age and dialysis duration are independent risk factors influencing cardiac valve calcification and aortic arch calcification.The calcium-phosphorus product is independent factor influencing cardiac valve calcification, with the highest danger coefficient,besides, the serum level of phosph is independent factor influencing aortic arch calcification, with the highest danger coefficient

peritoneal dialysis patients;heart valve calcification;aortic arch calcification;cardiovascular calcification

655000云南省曲靖市第二人民醫(yī)院腎病學科(陳關芬、辛麗芹)；昆明醫(yī)科大學第二附屬醫(yī)院(楊麗華)

R 459.51

A

1002-7386(2016)16-2409-04

2016-01-07)

doi:10.3969/j.issn.1002-7386.2016.16.002

項目來源：云南省科技計劃項目(編號：2012FB162)