卒中与高血压

卒中与高血压 上海交通大学医学院附属瑞金医院 上海市高血压研究所 王继光 n卒中在老年高血压患者中的危害 n降压治疗对老年高血压患者卒中风险的影响 nDHP-CCBs、ACEIs/ARBs、利尿剂以及受体阻断剂等 指南推荐的降压药物与卒中风险 n卒中风险与降压药物的血管作用 Incidence of Stroke in the Asian Pacific Region (2002) 127.6 105.9 97.3 72.6 68.4 65.5 57.0 56.3 43.2 42.4 41.0 39.9 31.0 020406080100120140 China Japan South Korea Vietnam Myanmar Laos Indonesia USA Cambodia Malaysia Singapore Thailand Philippines Incidence per 100,000 Atlas of Heart Disease and Stroke. MacKay J 3(suppl):14 -18; Li Liming, et al. ChinJ E pidemiol 2005;26:,478-484. PSC: Stroke mortality and usual BP 80-89 y 70-79 y 60-69 y 50-59 y Age at risk: Stroke mortality (floating absolute risk and 95% CI) 256 128 64 32 16 8 4 2 1 120140160180 Usual SBP (mm Hg) 80-89 y 70-79 y 60-69 y 50-59 y Age at risk: 708090100110 2 1 4 8 16 32 64 128 256 Systolic blood pressure Diastolic blood pressure Usual DBP (mm Hg) Prospective Studies Collaboration. Lancet 2002; 360: 190313. APCSC: stroke and usual BP 64.0 32.0 16.0 8.0 4.0 2.0 1.0 0.5 0.2 5 110120130140150 16 0 17 0 Usual systolic blood pressure (mmHg) l l l l l l l Age at risk 70 years 60-69 years 60 years Hazard ratio and 95% CI Asia Pacific Cohort Studies Collaboration. J Hypertens 2003;21:707716. n卒中在老年高血压患者中的危害 n降压治疗对老年高血压患者卒中风险的影响 nDHP-CCBs、ACEIs/ARBs、利尿剂以及受体阻断剂等 指南推荐的降压药物与卒中风险 n卒中风险与降压药物的血管作用 SystSyst-China-China SystSystolic Hypertension in olic Hypertension in ChinaChina Trial Trial J Hypertens 1998; 16:1823-1829. Arch Intern Med 2000; 160:211-220. 0123 4 10 8 6 4 2 0 12 Syst-China: Total mortality Deaths per 100 patients Follow-up (years) Placebo 39% Active treatment P=0.003 Liu LS et al. J Hypertens 1998;16:1823. 0123 4 2 1 0 3 Syst-China: Stroke mortality Deaths per 100 patients Follow-up (years) Placebo 58% Active treatment P=0.02 Liu LS et al. J Hypertens 1998;16:1823. 80 400+ 40% Syst-China: Fatal and non-fatal endpoints Liu LS et al. J Hypertens 1998;16:1823-1829. Placebo (n=1141 ) Total mortality CV mortality Stroke mortality All CV events Fatal and non-fatal stroke Active treatment (n=1253) Placebo better 82 44 20 94 59 61 33 10 74 45 Active treatment better -39 -39 -58 -37 -38 82 44 20 94 59 61 33 10 74 45 HYVET N Engl J Med. 2008;358:1887-98. HYVET: 研究设计 目标血压150/80 mmHg Beckett NS et al. N Engl J Med. 2008;358:1887-98. HYVET: 研究结果 Beckett NS et al. N Engl J Med. 2008;358:1887-98. 95% CIHR 0 (0.53, 0.82)0.66 (0.22, 0.58)0.36 (0.42, 1.19)0.71 (0.60, 1.01)0.77 (0.62, 1.06)0.81 (0.65, 0.95)0.79 (0.38, 0.99)0.61 (0.49, 1.01)0.70 心血管事件 心衰 心源性死亡 心血管死亡 NCV/不明死亡 全因死亡率 卒中死亡 所有卒中 Favors placebo Favors indapamide n卒中在老年高血压患者中的危害 n降压治疗对老年高血压患者卒中风险的影响 nDHP-CCBs、ACEIs/ARBs、利尿剂以及受体阻断剂等 指南推荐的降压药物与卒中风险 n卒中风险与降压药物的血管作用 CCBs vs. 利尿剂剂/阻滞剂剂: 致死性与非致死性脑脑卒中 利尿剂/阻滞剂CCBs 试验 事件数 / 研究对象人数 异质性检 验 危险比 (95%可信区间) 差别 (SD) 0 CCBs较好 123 利尿剂/阻滞剂较好 MIDAS/NICS/VHAS STOP2/CCBs NORDIL INSIGHT ALLHAT/Amlodipine ELSA CCBs without CONVINCE p = 0.68 CONVINCE 所有CCBsp = 0.39 15/1358 237/2213 196/5471 74/3164 675/15255 14/1157 1211/28618 118/8297 1329/36915 19/1353 207/2196 159/5410 67/3157 377/9048 9/1177 838/22341 133/8179 971/30520 10.2% (4.8) 2p = 0.02 7.6% (4.4) 2p = 0.07 Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 0123 UKPDS/Captopril STOP2/ACEIs CAPPP/Captopril ALLHAT/Lisinopril ANBP2/Enalapril All ACEIsp = 0.16 17/358 237/2213 148/5493 675/15255 107/3039 1184/26358 21/400 215/2205 189/5492 457/9054 112/3044 994/20195 10.2% (4.6) 2p = 0.03 ACEIs vs. 利尿剂剂/阻滞剂剂: 致死性与非致死性脑脑卒中 ACEIs较好利尿剂/阻滞剂较好 利尿剂/阻滞剂 试验 事件数 / 研究对象人数 异质性检 验 危险比 (95%可信区间) 差别 (SD) ACEIs Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76. 相对危险度 (95% CI) 赖诺普利 较好 氨氯地平 较好 +1% (9% to +11%)CHD +5% (3% to +13%) 总死亡率 +4% (3% to +12%) 联合CHD 脑卒中 联合CVD 需要住院的GI出血 心衰 心绞痛 冠脉血运重建 外周动脉疾病 0.51.02.0 +23% (+8% to +41%) +6% ( 0 to +12%) +20% (+6% to +37%) -13% (22% to 4%) +9% ( 0 to +19%) 0 (9% to +11%) +19% (+1% to +40%) P=0.055 P=0.047 P=0.003 P=0.007 P=0.004 P= 0.036 终点事件 差别 (95% CI) Leenen FHH, et al. Hypertension 2006;48:374-384. ALLHAT：赖诺普利 vs. 氨氯地平 氨氯氯地平 vs. ARBs*: 脑脑卒中 氨氯地平较好ARBs较好 IDNT VALUE CASE-J 所有试验 p = 0.46 30/579 322/7649 60/2354 412/10,582 18/567 281/7596 47/2349 346/10,51215.9% (6.2) 2p = 0.02 0.51.01.52.0 * 厄贝沙坦、缬沙坦、坎地沙坦 ARBs 氨氯地平 试验 事件数 / 研究对象人数 异质性检验 危险比 (95%可信区间) 差别 (SD) Wang JG et al. Hypertension 2007; 50:333-339. ASCOT-BPLA：一、二级终点 0.500.701.001.45 主要终点 非致死性MI(包括症状MI)+致死性冠心病 次要终点 非致死性MI(除外无症状MI)+ 致死性冠心病 总的冠心病终点事件 总的心血管病事件和操作 总死亡率 心血管病死亡率 致死性和非致死性脑卒中 致死性和非致死性心力衰竭 2.00 Unadjusted Hazard ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) Dahlf B et al. Lancet 2005:366;895-906. 氨氯地平 培哚普利较好 阿替洛尔 苄氟噻嗪较好 1.02.02.0 ACCOMPLISH: 主要终点及组成 复合复合CVCV发病率发病率/ /死亡率死亡率 心血管死亡率心血管死亡率 心梗心梗 中风中风 不稳定心绞痛住院不稳定心绞痛住院 冠状动脉成形术冠状动脉成形术 猝死复苏成功猝死复苏成功 危险比危险比 (95%)(95%) Aml / Ben 较好 0.80 (0.720.90)0.80 (0.720.90) 0.80 (0.62-1.03)0.80 (0.62-1.03) 0.78 (0.62-0.99)0.78 (0.62-0.99) 0.84 (0.65-1.08)0.84 (0.65-1.08) 0.75 (0.50-1.10)0.75 (0.50-1.10) 0.86 (0.74-1.00)0.86 (0.74-1.00) 1.75 (0.73-4.17)1.75 (0.73-4.17) Ben / HCTZ 较好 Jamerson K et al. N Engl J Med 2008;359:2417-28. n卒中在老年高血压患者中的危害 n降压治疗对老年高血压患者卒中风险的影响 nDHP-CCBs、ACEIs/ARBs、利尿剂以及受体阻断剂等 指南推荐的降压药物与卒中风险 n卒中风险与降压药物的血管作用 Markers of organ damage: ESH-ESC guidelines CV predictive AvailabilityCost value Electrocardiography+ Echocardiography+ Carotid IMT+ Arterial stiffness (PWV)+ ABI + Coronary calcium content+ J Hypertens 2007;25:1105-87. Stroke 2006;37:1933-40 CarotidCarotid IMT and IMT and antihypertensiveantihypertensive drugsdrugs A meta-analysis of RCTs Active treatment vs placebo/no treatment on IMT All ACEIs Heterogeneity 2 = 18.1 P = 0.003 BCAPS ELVA All Bs Heterogeneity 2 = 3.7 P = 0.05 PREVENT All trials Heterogeneity 2 = 25.9 P = 0.001 *Control:Active TrialDifference (m/y, 95% CI) Favours active treatment Favours control -1000100 -7 (-12 to -2) p = 0.01 n*Baseline IMT (m)* Change/y (m)* -5050 -10 (-33 to 13) p = 0.41 -6 (-12 to 0.4) p = 0.07929:1161 390:393 44:35 434:428 186:191 1549:1780 893:912 897:894 1258:1259 8:7 12:-12 11:-4 Wang JG et al. Stroke 2006;37:1933. CCBs vs diuretics/-blockers MIDAS VHAS INSIGHT ELSA All CCBs Heterogeneity 2 = 2.1 P = 0.55 *Old:CCB TrialDifference (m/y, 95% CI) Favours CCBs Favours old drugs -1000100 -5 (-9 to -1) p = 0.007 441:442 191:186 164:160 1012:1023 1808:1811