醫(yī)學(xué)專題在≥50歲就診高血壓患者中

1、北京大學(xué)人民醫(yī)院 王魯雁頑固性高血壓與動(dòng)脈病變2021/7/20 星期二1頑固性高血壓 定義頑固性高血壓是指盡管應(yīng)用了3種的降壓藥物，患者的血壓水平仍不能達(dá)到靶目標(biāo)，3種降壓藥物中最好有一種為利尿劑，所有藥物的劑量均已達(dá)到最佳。需要注意，這里3種降壓藥物的規(guī)定并無(wú)理論依據(jù)，其目的是識(shí)別有可能存在繼發(fā)性高血壓Hypertension，2008，517/20 星期二2頑固性高血壓常見(jiàn)臨床問(wèn)題，患病率不詳，在一些大規(guī)模的臨床試驗(yàn)中，有20 一30 的患者為頑固性高血壓。老齡和肥胖是導(dǎo)致血壓難以控制的兩種主要因素2021/7/20 星期二3頑固性高血壓收縮壓控制不滿意在Fra

2、mingham研究人群中，舒張壓控制在90mm Hg之內(nèi)的患者能達(dá)到90 ，而收縮壓140mm Hg的患者僅有49 。ALLHAT研究也發(fā)現(xiàn)有類似的問(wèn)題，有92 的患者舒張壓能控制在90mm Hg內(nèi)，僅有67 患者的收縮壓能達(dá)到30kgm )。舒張壓控制不滿意的因素中，最重要的是肥胖，有13的肥胖患者不能滿意控制舒張壓2021/7/20 星期二5頑固性高 血 壓老 齡 ？2021/7/20 星期二6高 血 壓小動(dòng)脈壁透明樣變性包括大動(dòng)脈在內(nèi)的所有動(dòng)脈動(dòng) 脈靶器官損害的根源2021/7/20 星期二7動(dòng) 脈小動(dòng)脈主動(dòng)脈的大分支，如無(wú)名動(dòng)脈、鎖骨下動(dòng)脈、頸總動(dòng)脈、髂動(dòng)脈、肺動(dòng)脈等主動(dòng)脈的其它分支，

3、如冠狀動(dòng)脈、腎動(dòng)脈和其它分配動(dòng)脈(distributing arteries)大動(dòng)脈（彈性動(dòng)脈）中動(dòng)脈（肌性動(dòng)脈）直徑2mm2021/7/20 星期二82021/7/20 星期二9動(dòng)脈與血壓形成勢(shì)能外周阻力存在，搏出量2/3儲(chǔ)存大A,使大A擴(kuò)張，對(duì)管壁施加側(cè)壓力（收縮壓）動(dòng)能 推動(dòng)搏出量的1/3在收縮期流向外周心室收縮射血 推動(dòng)大A內(nèi)血液繼續(xù)流向外周大動(dòng)脈彈性回縮 心臟舒張形成對(duì)管壁的側(cè)壓力（舒張壓）2021/7/20 星期二102021/7/20 星期二11150100501501005015010050(mmHg)(mmHg)(mmHg)Age 68 yearsAge 54 yearsAg

4、e 24 yearsRenalarteryaortaThoracicaortaAscendingaortaAbdominallliac arteryFemoralartery2021/7/20 星期二122021/7/20 星期二13舒張壓脈壓大 動(dòng) 脈 彈 性心舒期彈性 回縮力心縮期大A擴(kuò)張能力收縮壓大動(dòng)脈彈性2021/7/20 星期二14動(dòng)脈脈搏波分析(PWA)肱動(dòng)脈血壓壓力感受器動(dòng)脈骨骼140 70 70140函數(shù)轉(zhuǎn)換橈動(dòng)脈壓力波 中心動(dòng)脈壓力波2021/7/20 星期二15Augmentation Index (AIx)AIx = AP / PPSystoleDiastole2nd s

5、houlder1st shoulderAugmentation Pressure (AP)Pulse Pressure (PP)Ejection duration (msec)Diastolic duration IncisuraStart of the WaveP12021/7/20 星期二16脈搏波傳導(dǎo)速度（PWV）2021/7/20 星期二17動(dòng)脈結(jié)構(gòu)病變：粥樣硬化2021/7/20 星期二18Scheme of Atheromatous PlaqueMacrophagesT-lymphocytesAtheromatous plaqueLumenFibrous capEndothelia

6、l cells2021/7/20 星期二192021/7/20 星期二202021/7/20 星期二212021/7/20 星期二22高血壓患者臨床特征及其與頸動(dòng)脈粥樣硬化之間的關(guān)系 （n=224）無(wú)頸動(dòng)脈粥樣硬化合并頸動(dòng)脈粥樣硬化年齡（歲）52.529.9064.7411.20*體重指數(shù)（BMI）26.173.4425.893.50收縮壓（mmHg）149.6223.67152.6621.59舒張壓（mmHg）91.1913.9885.9012.24*脈壓（mmHg）58.4316.5766.7616.77*高血壓病程（年）8.5610.3412.1611.30*2021/7/20 星期二2

7、3Prevalence of PAD increases with ageFigure adapted from Creager M, ed. Management of Peripheral Arterial Disease. Medical, Surgical and Interventional Aspects. 2000. 1 Meijer WT et al. Arterioscler Thromb Vasc Biol 1998; 18: 185-192.2.Criqui MH et al. Circulation 1985; 71: 510-515. Patients with PA

8、D (%)Rotterdam Study (ABI Test 0.9)1 San Diego Study (PAD by noninvasive tests)22021/7/20 星期二24Newman AB et al. Circulation 1993; 88: 837-845. TASC Working Group. J Vasc Surg 2000; 31 (1, pt 2): S1-S288. Djousse PM et al. Circulation 2000; 102: 3092-3097.Risk factors for PADSmokingDiabetesHypertensi

9、onHypercholesterolemiaAlcohol0.75 1 2 3 4 56Relative RiskReducedIncreased2021/7/20 星期二25Mortality is very high in patients with severe PADRelative 5-year mortality1. Criqui MH. Vasc Med 2001; 6 (suppl 1): 37. 2. McKenna M et al. Atherosclerosis 1991; 87: 11928. 3. Ries LAG et al. (eds). SEER Cancer

10、Statistics Review, 19731997. US: National Cancer Institute; 2000.Patients (%)05101520253035404550Colon/rectalcancer1Breast cancer1SeverePAD2Non-Hodgkinslymphoma3153844482021/7/20 星期二26PREVENT: 頸動(dòng)脈內(nèi)膜中層厚度(IMT)內(nèi)膜中層厚度變化(mm)苯磺酸氨氯地平Pitt et al. Circulation 2000;102:1503-10P=0.007安慰劑 0.033 0.0132021/7/20 星期

11、二27CAMELOT/NORMALISE:阻遏和消退冠狀動(dòng)脈粥樣硬化的進(jìn)展Nissen et al, for the CAMELOT investigators. JAMA. 2004;292:2217-2226.安慰劑(n=49)依那普利(n=40)苯磺酸氨氯地平(n=47)P平均值患者N=136P0.01P=0.20P=0.76粥樣斑塊體積百分比的改變 (%)2021/7/20 星期二28AVALON-AWC:有效改善動(dòng)脈彈性動(dòng)脈彈性較基線改善程度(%)大動(dòng)脈彈性指數(shù)(C1)小動(dòng)脈彈性指數(shù)(C2)小動(dòng)脈彈性指數(shù)(C2)苯磺酸氨氯地平苯磺酸氨氯地平+阿托伐他汀American Society

12、 of Hypertension 20th Annual Scientific Meeting and ExpositionMay 14 - 18, 2005, San Francisco, California2021/7/20 星期二29ASCOT/CAF：中心動(dòng)脈壓0 1.0 2.0 3.0 4.0 5.0 6.0(年)133.9133.2125.5121.2苯磺酸氨氯地平組(n=1042)阿替洛爾組(n=1031)外周收縮壓: 平均差異(AUC)=0.7(-0.4-1.7)mmHg,P=0.2中心收縮壓:平均差異(AUC)=4.3(3.3- 5.4)mmHg,P70)ACC/AHA 2

13、005 Guidelines for the Management of Patients With Peripheral Arterial Disease2021/7/20 星期二32頑固性高血壓-腎動(dòng)脈狹窄頑固性高血壓患者中腎動(dòng)脈狹窄更為常見(jiàn)，尤其是老年患者。在50歲就診高血壓患者中，有12.7為繼發(fā)性高血壓，最常見(jiàn)的繼發(fā)性高血壓是腎動(dòng)脈狹窄，占35 。2021/7/20 星期二33腎動(dòng)脈狹窄 病因RAS：動(dòng)脈粥樣硬化、大動(dòng)脈炎、纖維肌性營(yíng)養(yǎng)不良等。動(dòng)脈粥樣硬化是RAS的主要病因，大多是彌漫性動(dòng)脈粥樣硬化的全身表現(xiàn)之一，占80 85。局限于腎臟的動(dòng)脈粥樣硬化僅占15 202021/7/20

14、 星期二34慢性缺血性腎病CIRD(chronic ischemic renal disease)因腎動(dòng)脈狹窄或阻塞(超過(guò)60)，腎血流動(dòng)力學(xué)顯著改變而致腎小球?yàn)V過(guò)率下降，腎功能不全的慢性腎臟疾病。需要注意的是，雖然腎動(dòng)脈狹窄(RAS)或腎血管性高血壓與慢性缺血性腎病關(guān)系密切，并不等同于慢性缺血性腎病，因早期腎動(dòng)脈狹窄或腎血管性高血壓可不引起腎功能異常，此時(shí)尚不能診斷。2021/7/20 星期二35膽固醇結(jié)晶栓塞是CIRD的另一個(gè)重要原困。隨著人口的老齡化，動(dòng)脈粥樣硬化性疾病的增多和介入技術(shù)的普及成用，膽固醇結(jié)晶引起的多發(fā)栓塞疾病也日益增多，并稱之為膽固醇栓塞綜合征2021/7/20 星期二3

15、6慢性缺血性腎病 病理改變腎小管 ，所有結(jié)構(gòu)都可累及。小管損傷：小管上皮細(xì)胞脫落、凋亡或灶性壞死。腎小管萎縮、局灶 質(zhì)炎癥反應(yīng)，腎小管硬化，形成“無(wú)腎小管的腎小球” 腎血管：腎小動(dòng)脈中層增厚、玻璃樣變，弓形動(dòng)脈纖維彈性組織變性，動(dòng)脈栓塞(膽固醇碎片局灶梗死)腎小球的改變多繼發(fā)于腎小管和腎血管的病變，最后導(dǎo)致腎小球硬化，腎皮質(zhì)瘢痕彤成、腎萎縮。2021/7/20 星期二37Clinical Clues to the Diagnosis of RASonset of hypertension before 30 yonset of severe hypertension after 55 yAcc

16、elerated hypertension/resistant hypertension/ malignant hypertensionACC/AHA 2005 Guidelines for the Management of Patients With Peripheral Arterial Disease2021/7/20 星期二38new azotemia or worsening renal function after the administration of an ACEI or ARBunexplained atrophic kidney or a discrepancy in

17、size between the 2 kidneys of greater than 1.5 cmsudden, unexplained pulmonary edemaClinical Clues to the Diagnosis of RASACC/AHA 2005 Guidelines for the Management of Patients With Peripheral Arterial Disease2021/7/20 星期二39臨床特點(diǎn)高血壓發(fā)生年齡小于30歲或大于55歲（嚴(yán)重）；突發(fā)進(jìn)行性血壓高血壓患者合并2級(jí)以上視網(wǎng)膜病變，用3種或3種以上全量的抗血壓藥物仍不能控制血壓，或

18、高血壓患者反復(fù)發(fā)生肺水腫；半年內(nèi)迅速進(jìn)展的惡性高血壓，以前穩(wěn)定的高血壓突然惡化，使用抗血壓藥物(尤其是ACEI)治療后腎功能惡化；老年人或高血壓患者m現(xiàn)不能解釋的氯質(zhì)血癥；腹部或腰部血管雜音；不能解釋的雙腎不對(duì)稱或一側(cè)或兩側(cè)血流減少。2021/7/20 星期二40檢測(cè)手段超聲雙腎大小不對(duì)稱提示RAS（長(zhǎng)徑8 cm且無(wú)回聲增強(qiáng)，腎臟尚可挽救），大小對(duì)稱并不能完全排除RAS雙功多普勒結(jié)合B型超聲及多普勒超聲 可在形態(tài)學(xué)及血流動(dòng)力學(xué)兩方面進(jìn)行觀察，其敏感性及特異性均可達(dá)80%以上2021/7/20 星期二41CDFI(color Doppler flow imaging)：彩色多普勒血流顯像：可顯示

19、腎內(nèi)動(dòng)、靜脈血管床，觀察血管走行及分布，PWD(pulsed wave Doppler)：脈沖多普勒頻譜適合于較嚴(yán)重70%的狹窄，對(duì)于較輕狹窄其靈敏性和特異性均較低，PDI(power Doppler imaging)：能量多普勒成像反映血管的內(nèi)邊界更清晰，較準(zhǔn)確地反映狹窄部位的血管形態(tài)，可以看見(jiàn)小于60% 的狹窄2021/7/20 星期二42螺旋CT血管造影(cTA)優(yōu)勢(shì)：無(wú)創(chuàng)傷，不僅能提供管腔，而且能提供管壁及相鄰血管與組織結(jié)構(gòu)的病理改變，對(duì)鈣斑和血栓的顯示更佳。CTA 能顯示大部分腎副動(dòng)脈和部分腎內(nèi)動(dòng)脈分支，但對(duì)直徑小于2mm，開(kāi)口部位變異的腎副動(dòng)脈和管徑小，難于強(qiáng)化的腎實(shí)質(zhì)相鑒別的腎內(nèi)

20、動(dòng)脈分支顯影困難。X線血管造影檢查(DsA2021/7/20 星期二43螺旋CT血管造影(CTA)磁共振血管成像(MRA) X線血管造影檢查(DsA）MRA 的空間分辨力低于CTA，對(duì)腎副動(dòng)脈及腎動(dòng)脈分支的顯示不如CTA，僅能顯示管徑大的腎副動(dòng)脈和小部分腎內(nèi)分支。對(duì)于判定RAS 50 %者，CTA 和MRA 的敏感度和特異度分別為88 96 % ，77 98 % ，和84 100 % ，90 99 % ；MRA 判斷RAS 70%者較CTA準(zhǔn)確，但MRA檢查時(shí)間長(zhǎng)，對(duì)急危重病人檢查受限CTA和MRA檢測(cè)RAS均有高估現(xiàn)象，有假陽(yáng)性和偶有假陰性，且CTA 診斷RAS 70 %者易誤診或過(guò)診為閉塞

21、，2021/7/20 星期二44腎動(dòng)脈狹窄的治療包括介入治療，外科治療和藥物治療。藥物治療同高血壓患者，雙側(cè)狹窄禁用ACEI和ARB介入治療包括經(jīng)皮腔內(nèi)雙腎動(dòng)脈血管成形術(shù)(PTRA)和動(dòng)脈內(nèi)支架置入術(shù)。外科治療包括腎血管旁路移植術(shù)、腎動(dòng)脈內(nèi)膜剝脫術(shù)、腎動(dòng)脈再移植術(shù)、腎動(dòng)脈狹窄段切除術(shù)、離體腎動(dòng)脈成形術(shù)、自體腎移植術(shù)及腎切除術(shù)等。2021/7/20 星期二45藥物治療AECICCBBBARB2021/7/20 星期二46Blood Pressure Outcome of Angioplasty in Atherosclerotic Renal Artery Stenosis A Randomiz

22、ed Trialatherosclerotic nature of the RAS a reduction in arterial diameter of either 75% without thrombosis or of 60% with a positive lateralization test a stenosis affecting the main renal artery, which had not been previously dilated a functional kidney on the opposite side exhibiting a normal mai

23、n artery or an arterial diameter reduction 50%. Hypertension. 1998;31:823-829 2021/7/20 星期二47Trial profile antihypertensive agents were prescribed in the following sequence: slow-release nifedipine 20 mg BID; idem plus clonidine 0.15 mg BID; idem plus prazosin, 2.5 mg daily. diastolic BP exceeded 10

24、9 mm Hg on first outpatient visit or 95 mm Hg on two successive visits, atenolol 50 mg/d, furosemide 40 mg/d, or enalapril 10 mg/d was added 2021/7/20 星期二48DDD (defined daily dose ): nifedipine 30 mg, clonidine 0.45 mg, prazosin 5 mg, furosemide 40 mg, enalapril 10 mg, and atenolol 75 mg 2021/7/20 星

25、期二49Difference in blood pressure reduction (mean and 95% confidence interval) between patients allocated to medical treatment and those allocated to angioplasty by the method of blood pressure assessment. 2021/7/20 星期二50CONCLUSIONangioplasty made BP control easier in the short term but was more freq

26、uently associated with complications than conservative management in patients with unilateral atherosclerotic RAS. Most patients undergoing angioplasty still needed antihypertensive agents 6 or 12 months after the procedure. The reduction in treatment required by patients undergoing angioplasty shou

27、ld therefore be weighed against the risks of complications and restenosis. 2021/7/20 星期二51Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function Design: Randomized clinical trialSetting: 10 European medical centers. Participants: 140 patients with creatini

28、ne clearance less than 80 mL/min per 1.73 m2 and ARAS of 50% or greater. Intervention: stent placement and medical treatment /medical treatment only (diuretics, calcium antagonists, -blockers, and -blockers, followed by angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and increasing doses of diuretics if first-line antihypertensive treatment failed ), a statin, and aspirin. The primary end point : 20% or greater decrease i