【正文】 and the corresponding standard deviation). ? Dipping or nondipping (nocturnal BP fall 10% or 10% of the daytime values). ? Reduction of microalbuminuria (in subgroup of patients). ? Metabolic parameters (fasting blood glucose, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides). ? Markers of inflammation: ? Soluble receptors for advanced glycation end products [sRAGE] pg/mL – a low level of which implies higher risk ? Eotaxin3 pg/mL – a low level of which implies higher risk ? Creactive protein mg/dL – a high level of which implies higher risk. 125 TALENT Study 126 Initial findings of TALENT ? Combination therapy with nifedipine GITS/telmisartan in TALENT lowered office and 24h BP in hypertensive patients at high CV risk Office and 24h BP were reduced by , respectively。 ? BP reduction with the bination of nifedipine GITS/telmisartan in TALENT was consistent throughout the 24h period。 ? Initiating antihypertensive treatment with the bination of nifedipine GITS/telmisartan allowed BP control to be achieved earlier pared with starting with one drug and then adding a second。 ? Optimum BP reduction was achieved as early as two weeks and was maintained throughout the study。 127 TALENT研究的啟示 1,在爭取血壓達標時不可操之過急 ,應(yīng)注意 J曲線 問題 ! 2,起始采取聯(lián)合用藥較用單藥可較早達標 。 3,起始聯(lián)合用藥雖可較早達標 ,但對 長期控制血壓并無優(yōu)勢 。 4,在實施降壓時 ,不要特意強調(diào)哪種途徑最好 ,如大力肯定固定復方制劑；大力提倡起始聯(lián)合治療等 ,而應(yīng)根據(jù)不同患者特點采取多元聯(lián)合治療途徑 ! 128 Summary ?Mean BP in trial has minimal effect on stroke oute and no effect on CHD oute ? Various measures of visittovisit BP variability (SD, coefficient of variation and variation independent of mean BP) are powerful predictors of both stroke and CHD outes ? Other measures of variability (withinvisit variability and variability assessed by ABPM) also predict cardiovascular outes but less than visittovisit variability ? Amlodipine reduces variability pared with atenolol ? Variability increased with age, diabetes, smoking, and in those with established vascular disease ? Adjusting for BP variability pletely explains differences in stroke and CHD outes between amlodipinebased and atenololbased treatment in ASCOT 129 130 1997。80。1453~1458 131 優(yōu)良抗高血壓藥的新標準 ━ 不僅降低平均收縮壓而應(yīng)有效降低收縮壓的變異性 ? 收縮壓和收縮壓負荷可導致心、腦、腎損傷，故有效的降血壓藥物應(yīng)該 有效地降低收縮壓的變異性，而不是僅僅降低平均收縮壓 。老年人抗高血壓治療可明顯降低心血管疾病的發(fā)病率及死亡率。夜間血壓水平對是否容易引起腦血管并發(fā)癥比白晝或總體血壓水平更為重要，較低的夜間血壓對腦血管有保護性作用，但值得注意的是， 一般認為短效降壓藥物增加血壓變異，長效降壓藥則可達到 24小時內(nèi)的穩(wěn)定降壓 和減少血壓變異 。 132 優(yōu)良抗高血壓藥的新標準 ━ 不僅降低平均收縮壓而應(yīng)有效降低收縮壓的變異性 ? 大量研究表明， BPV增加與血管事件尤其是卒中的高風險密切相關(guān) ,是預測卒中風險的強指標 ,且獨立于平均 SBP,因此 ,能有效控制 24h血 ,降低 BPV的藥物可能將為高血壓患者帶來更多效益 ,目前抗高血壓藥物中 ,長效 CCB對 BPV影響相對更具有優(yōu)勢 。 ? 此外 ,BPV是隨年齡增加而增加 ,但對年輕患者的預測價值更高 ,故建議 55歲高血壓患者首選長效CCB! 133 美國高血壓協(xié)會推薦要點 (2022,4) 1,聯(lián)合用藥是降壓達標的常規(guī)方法； 2,以兩藥聯(lián)合用藥為主； 3,欲降低 ≥ 20/10mg方能達標者 ,初始即可聯(lián)合用藥 。 4,高血壓 Ⅰ 期患者為改善單藥的不良反應(yīng) ,亦可聯(lián)合用藥 。 5,固定復方聯(lián)合用藥不利于個體化 ,應(yīng)權(quán)衡利弊使用。 134 哪些患者適用聯(lián)合用藥 ? 135 哪些患者適用聯(lián)合用藥 ? 136 FDCs—臨床的選擇 Coexisting condition First choice Ischaemic heart disease Amlodipine + Atenolol Diabetes Amlodipine + Lisinopril Amlodipine + Losartan Hyperlipidemia Amlodipine + Lisinopril Amlodipine + Losartan Congestive heart failure Lisinopril + HCTZ Losartan + HCTZ Tachycardia Amlodipine + Atenolol Bradycardia Amlodipine + Lisinopril Amlodipine + Losartan Asthma/COPD Amlodipine + Losartan Amlodipine + Lisinopril Elderly hypertensives Amlodipine + Losartan Amlodipine + Lisinopril Lisinopril/Losartan + HCTZ 137 FDCs—不同患者 的臨床選擇 Coexisting condition First choice Peripheral vascular disease Amlodipine + Lisinopril Amlodipine + Losartan Losartan + HCTZ Lisinopril + HCTZ Gout Amlodipine + Lisinopril Amlodipine + Losartan Amlodipine + Atenolol Anxiety Amlodipine + Atenolol Depression Amlodipine + Lisinopril Amlodipine + Losartan Lisinopril + HCTZ Losartan + HCTZ Renal insufficiency (not due to renal Amlodipine + Lisinopril artery stenosis) Amlodipine + Losartan 138 Intervention Exercise Weight reduction Alcohol intake reduction Sodium intake reduction DASH diet 藥物降圧切不可忽視生活方式的改善 Blood Pressure Effect 510 mm Hg (30 min 3x/wk) 12 mm Hg/Kg? 1 mm Hg/drink/d? 13 mm Hg/40 mmol/d? 310 mm Hg ? Adapted from Cushman et al. Endocrine Practice 1997。3:106 amp。 Sacks, et al. NEJM 2022。334:3 過去治療方案 BP Cholesterol Disease Disease Treatment Treatment Normal Normal GOAL: Target Response 當代治療方案 DISEASE BP Cholesterol GOAL: ?Target Response TREATMENT 未來治療方案 Early Disease Statin RAAS Blockade Antihypertensives NO donor/enhancer Innovative Therapy Slow Progression GOAL: ?Target Dose 142 聯(lián)合用藥 — 未來的方向 疾病治療需要多靶點 143 當代高血壓藥物治療的策略 (聯(lián)合用藥的基礎(chǔ)是 CCB。還可獲得多種降壓外的有益作用 )。 144 世界高血壓聯(lián)盟強烈呼吁 !!! 行動起來 !讓更多的高血壓患者降壓達標 ! 145 謝謝大家參與