老年高血壓患者raas特點(diǎn)分析及其治療對(duì)策

1、老年高血壓患者RAAS特點(diǎn)分析及其治療對(duì)策,CN.IRB.15.01.18,RAAS名稱(chēng)使用的注意事項(xiàng),,,,,常見(jiàn)筆誤或口誤：如RAAS系統(tǒng)，S已表明是系統(tǒng),RAS：Renin-Angiotensin System，血管緊張素II促使醛固酮分泌，醛固酮可反射性抑制腎素分泌,RAAS：Renin-Angiotensin-Aldosterone System,,1. Perico Int J Clin Pract Suppl 11

2、1; 14,對(duì)RAAS的傳統(tǒng)認(rèn)識(shí),緩激肽釋放,血管擴(kuò)張NO生成凋亡激肽釋放,RAAS中血管緊張素Ⅱ和醛固酮是發(fā)揮生物作用的效應(yīng)分子,血管緊張素Ⅱ,是強(qiáng)大的血管收縮物質(zhì)（僅次于內(nèi)皮素）是強(qiáng)大的促細(xì)胞增殖物質(zhì)（通常在血壓升高前引起血管和心肌肥厚）是重要的生理物質(zhì)（生長(zhǎng)發(fā)育、水電平衡等生理功能的必需物）等,醛固酮,保鈉排鉀，水鈉儲(chǔ)留促細(xì)胞增殖反射性抑制腎素分泌等,Plasma Renin Activity Levels in

3、Hypertensive Persons:(10.1016/j.amjhyper.2003.08.015,健康人腎臟隨年齡增長(zhǎng)結(jié)構(gòu)發(fā)生多重改變體積越來(lái)越小，硬化程度加重,2. D. Bolignano et al. The aging kidney revisited: A systematic review. Ageing Research Reviews 14 (2014) 65–80,老年腎臟的多方面功能改變,2. D. Bol

4、ignano et al. The aging kidney revisited: A systematic review. Ageing Research Reviews 14 (2014) 65–80,導(dǎo)致二個(gè)基本結(jié)局：水鈉儲(chǔ)留容量擴(kuò)張低RAAS活性易導(dǎo)致老年人水電解質(zhì)異常如脫水,高鈉和高鉀,正常血壓老年人腎素活性下降至青年人的一半,3. Noth, R.H., Lassman, M.N., Tan, S.Y et al.

5、Age and the renin–aldosterone system. Archives of Internal Medicine 1977; 137, 1414–1417.,,,然而，老年高血壓患者腎素活性卻增加Plasma Renin Activity Levels in Hypertensive Persons: Their WideRange and Lack of Suppression in Diabetic a

6、nd in Most Elderly PatientsN=4170,4. Michael H. Alderman, Hillel W. Cohen, Jean E. Sealey, and John H. Laragh. Plasma Renin Activity Levels in Hypertensive Persons: Their Wide Range and Lack of Suppression in Diabetic a

7、nd in Most Elderly Patients . AJH 2004;17:1–7,,Plasma renin activity distribution by age,,,老年對(duì)Ang II反應(yīng)過(guò)度,實(shí)驗(yàn)表明：老年對(duì)Ang II反應(yīng)過(guò)度,5. Tank JE, Vora JP, Houghton DC, Anderson S. Altered renal vascular responses in the aging rat

8、kidney. Am J Physiol 1994;266:F942-F948. 6. Hye Eun Yoon and Bum Soon Choi . The renin-angiotensin system and aging in the kidney . Korean J Intern Med 2014;29:291-295,但是，對(duì)RAAS抑制劑ARB的反應(yīng)保留,ARB良好的降壓療效,7. Fabia MJ, et al.

9、 J Hypertens. 2007;25:1327-1336,24h平均下降值,ESH/ESC 2013 ARB類(lèi)藥物優(yōu)先適用的情況，尤其是腎臟保護(hù)作用,這些與血壓高/細(xì)胞增殖有關(guān)常見(jiàn)的合并癥,8 .G. Mancia et al.Journal of Hypertension 2013;31:1281-1357,左心室肥厚微量白蛋白尿腎功能不全既往卒中既往心肌梗死,心衰預(yù)防房顫ESRD/蛋白尿代謝綜合征糖尿病,JN

10、C8強(qiáng)調(diào)的健康終點(diǎn)第一次包括腎臟,健康終點(diǎn)（死亡率；心、腦、腎、血管）死亡率：總死亡率，心血管疾?。–VD）相關(guān)死亡率，CKD相關(guān)死亡率心肌梗死，心力衰竭，心衰住院，冠脈血運(yùn)重建術(shù)（包括冠脈旁路移植術(shù)，冠脈成形術(shù)和冠脈支架術(shù)）卒中終末期腎臟疾病（ESRD）（腎衰竭導(dǎo)致透析或移植），肌酐水平增加一倍，腎小球?yàn)V過(guò)率（GFR）下降50%其他動(dòng)脈血運(yùn)重建（包括頸動(dòng)脈、腎動(dòng)脈、下肢動(dòng)脈血運(yùn)重建）,9. JAMA. 2014;311(5)

11、:507-520.,腎臟健康終點(diǎn)非常重要！,,經(jīng)年齡調(diào)整的冠心病死亡率總體下降53.2%*Age-adjusted to the 1940 U.S. census population.,不同性別和種族的冠心病患者經(jīng)年齡調(diào)整的死亡率百分比下降：美國(guó)（1972-1994）,10. Arch Intern Med. 1997 Nov 24;157(21):2413-46,14,,經(jīng)年齡調(diào)整的冠心病死亡率總體下降59.0%. *Age-

12、adjusted to the 1940 U.S. census population.,不同性別和種族的卒中患者經(jīng)年齡調(diào)整的死亡率百分比下降：美國(guó)（1972-1994）,10. Arch Intern Med. 1997 Nov 24;157(21):2413-46,終末期腎病的發(fā)病率（1982-1995）,15,,253*,*Provisional data.Adjusted for age, race, and sex.,1

13、0. Arch Intern Med. 1997 Nov 24;157(21):2413-46,解決終末期腎病是當(dāng)今社會(huì)面臨的重大課題實(shí)際上，我們有了解決這一問(wèn)題的辦法,JNC8強(qiáng)調(diào)RASI改善腎臟結(jié)局的重要性,年齡＞18歲合并慢性腎臟疾病 的患者應(yīng)選用ACEI或ARB行起始或疊加降壓治療以改善腎臟結(jié)局。該推薦適用于各種族、合并及不合并糖尿病的所有高血壓患者。 強(qiáng)調(diào)特定的藥物對(duì)腎臟預(yù)后的潛在獲益Recommendation 8 i

14、s specifically directed at those with CKD and hypertension and addresses the potential benefit of specific drugs on kidney outcomes.,9. JAMA. 2014;311(5):507-520.,11. Collaborative Study Group. Renoprotective effect of t

15、he angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Lewis EJ, Hunsicker LG, ClarkeWR, et al; N Engl J Med. 2001;345(12):851-860.,We randomly assigned 1715 hypertensive patie

16、nts with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo.同時(shí)具備高血壓、腎病、2型糖尿病的RCT,一級(jí)終點(diǎn)：肌酐水平增加一倍、終末期腎臟疾?。‥SRD）、任何原因死亡,厄貝沙坦顯著降低一級(jí)終點(diǎn)20%與安慰劑(P=0.02)23%與氨氯地

17、平(P=0.006),11. Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Lewis EJ, Hunsicker LG, ClarkeWR, et al; N Engl J Med

18、. 2001;345(12):851-860.,11. Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Lewis EJ, Hunsicker LG, ClarkeWR, et al;

19、 N Engl J Med. 2001;345(12):851-860.,這種差異與血壓無(wú)關(guān),,Mean blood pressure decreased over the course of the study 140/77 mm Hg in the irbesartan group, 141/77 mm Hg in the amlodipine group, 144/80 mm Hg in the placebo group.

20、,指南推薦厄貝沙坦RCT靶劑量為300mg,,11. Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Lewis EJ, Hunsicker LG, ClarkeWR, et al;

21、N Engl J Med. 2001;345(12):851-860.,JNC8 引用的降低腎終點(diǎn)事件的RCT,三大試驗(yàn)均強(qiáng)調(diào)RAAS抑制劑治療這種差異與血壓無(wú)關(guān),9. JAMA. 2014;311(5):507-520.,降壓治療顯著減少CV終點(diǎn)事件147項(xiàng)隨機(jī)臨床試驗(yàn)的薈萃分析,12. Law MR, et al. BMJ. 2009;338:b1665,For reduction of 10mmHg SBP and/or 5mm

22、Hg DBP,Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome,Materials/Methods. We used the Cardiovascular Health Study, a prospective cohort study

23、of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free

24、 of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.,13. metabolism clinical and experimental 63

25、(2014):392-399,高血壓一般人群無(wú)論用何種藥物，如果降壓一樣，心血管獲益一樣。但是，這個(gè)結(jié)果表明：老年高血壓伴代謝異?；颊?，RAS抑制劑可更多降低心血管事件。,RAS抑制劑在老年高血壓治療中的重要地位及注意事項(xiàng),RAS抑制劑有效降低老年高血壓患者的死亡率、心血管事件發(fā)生率、和改善腎終點(diǎn)老年高血壓患者應(yīng)用RAS抑制劑應(yīng)監(jiān)測(cè)血鉀和腎功能RAS抑制劑應(yīng)用2個(gè)月內(nèi)血清肌酐上升30%以內(nèi)，而且穩(wěn)定，表明可改善預(yù)后和保

26、護(hù)腎功能,14. Faruk Turgut, Rasheed A. Balogun, and Emaad M. Abdel-Rahman. Renin-Angiotensin-Aldosterone System Blockade Effects on the Kidney in the Elderly: Benefits and Limitations. Clin J Am Soc Nephrol 5: 1330–1339, 2010

27、,The only trial directly comparing two combinations in all patients (ACCOMPLISH) found significant superiority of an ACE inhibitor-calcium antagonist combination over the ACE inhibitor-diuretic combination despite there

28、 being no BP difference between the two arms. These unexpected results deserve to be repeated, because trials comparing a calcium antagonist-based therapy with a diuretic-based therapy have never shown superiority of the

29、 calcium antagonist.,唯一的試驗(yàn)直接比較兩個(gè)組合發(fā)現(xiàn)ACEI+鈣拮抗劑的組合顯著優(yōu)于ACEI+利尿劑。這些意外的結(jié)果需要重復(fù)試驗(yàn)，因?yàn)橐酝囼?yàn)比較鈣拮抗劑為基礎(chǔ)的治療與利尿劑為基礎(chǔ)的治療從未表現(xiàn)出鈣拮抗劑的優(yōu)勢(shì)。,是ACEI+鈣拮抗劑還是ACEI+利尿劑,2013 ESH/ESC Guidelines for themanagement of arterial hypertension,8 .G. Mancia e

30、t al.Journal of Hypertension 2013;31:1281-1357,15. 孫寧玲主編 .高血壓治療學(xué).北京;人民衛(wèi)生出版社:2009,厄貝沙坦/氫氯噻嗪既作用于血管收縮又作用于容量擴(kuò)張契合老年高血壓特點(diǎn),,厄貝沙坦/氫氯噻嗪治療中國(guó)老年高血壓患者療效卓著,起效迅速，治療第1周可降低收縮壓達(dá)13mmHg強(qiáng)效降壓，治療第4周可降低收縮壓達(dá)26mmHg,16. 謝玉蘭等，現(xiàn)代醫(yī)學(xué)2006;34(6):417-

31、9,Robert Petrella, et al, Clinical Therapeutics 2011;33(9):1190-1203,聯(lián)合治療:厄貝沙坦/HCTZ比其他ARB /HCTZ減少心血管事件,,2011年回顧分析：Retrospective Analysis of Real-World Efficacy of Angiotensin Receptor Blockers Versus Other Classes of An

32、tihypertensive Agents in Blood Pressure Management,— 真實(shí)世界，ARB與其他類(lèi)別藥物降壓療效的比較,17. Petrella R, Michailidis P. Retrospective analysis of real-world efficacy of angiotensin receptor blockers versus other classes of antihypert

33、ensive agents in blood pressure management. Clin Ther. 2011;33(9):1190-203,對(duì)利尿劑的過(guò)多擔(dān)心：利尿劑相關(guān)的糖代謝異常與大劑量利尿劑引起的低血鉀有關(guān),18 ZIHkb, A J, et al. Hypertension 2006;40:219-224,厄貝沙坦150mg+HCTZ12.5mg對(duì)血鉀的影響<0.1mEq/L,厄貝沙坦可抵消12.5mgHCT