医学课件糖尿病患之高血壓症

糖尿病患之高血壓症,國立成功大學醫學院附設醫院 內科部內分泌新陳代謝科 吳達仁 醫師,Diabetes and Hypertension,Hypertension occurs with twice the frequency in the diabetic population as compared with the general, non-diabetic population. 50% of patients diagnosed with diabetes eventually become hypertensive.,Christlieb AR. Diabetes 1981：30 (Suppl 2):90,The age- and sex-adjusted prevalence of hypertension among diabetic subjects was twice that of non-diabetic subjects (39.6% vs 16.4%) in TAIWAN. 2. Hypertensive subjects had a higher prevalence of diabetes than normotensive subjects (10.2% vs 4.9%).,Tai TY, et al. Diabetes Care 1991:14:1031.,T-J WU,高血壓病患有較高的糖尿病發生率,追蹤之8年發生率 (每1000人年 發生案例),Gress TW et al. N Engl J Med. 2000;342:905-912.,正常血壓 n=8746,高血壓 n=3804,T-J WU,高血糖值增加高血壓之風險,高 血 壓 之 風 險,葡萄糖負荷後90分鐘之血糖值,Kristianson K et al. J Hypertens. 1995;13:581-586.,Male n= 2639,Female n= 2346,追蹤: 3-8 年,3,5.8,7,10,13,1.8 1.4 1.0 0.6,T-J WU,高血壓糖尿病主要併發症之風險,發生率 (%),Hypertension in Diabetes Study Group. J Hypertens. 1993;11:319-325.,UKPDS 3648位新診斷第2型糖尿病人4-6年之追蹤,致死性 非致死性 狹心症 腦卒中 所有死亡 冠心病 冠心病,糖尿病與收縮高血壓症：增加心血管病風險,每1000人-年發生 心血管病事件,1. SHEP Cooperative Research Group. JAMA. 1991;265:3255-3264. 2. Staessen JA et al. Lancet. 1997;350:1757-1764. 3. Wang JG et al. Arch Intern Med. 2000;160:221-228.,SHEP1 SYST-EUR2 SYST-CHINA3,高血壓在糖尿病病患的重要性,高血壓是糖尿病患極為常見之共犯結構。約2060% 糖尿病患患有高血壓。 在第2型糖尿病患之高血壓，經常是以胰島素抗性為特徵之代謝症候群(metabolic syndrome)的主要成員之一。 在第1型糖尿病患之高血壓則經常是反應著糖尿病腎臟病變(diabetic nephropathy)的開始。 高血壓會增加糖尿病患大血管併發症 (macrovascular) 與 微細血管併發症 (microvascular complications)之風險包括腦卒中、冠心病、週邊血管病變、 網膜病變、及腎臟病變。 由最近幾年累積下來嚴謹的RCT (randomized clinical trials) 資料証實：積極治療糖尿病患之高血壓是可以改善大血管與微細血管病變。,T-J WU,降低血壓有助減低糖尿病相關併發症之風險,嚴密控制血壓(144/82 mm Hg)相對於一般血壓控制 (154/87mm Hg)減低糖尿病相關併發症風險之比率 其功效甚於降血糖 (HbA1c 由 7.9% 降至 7%) 降血壓 降血糖 - 32%* 10% - 24%* 12% - 44%* NA - 56%* NA - 37%* 25%,UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.,糖尿病相關死亡 糖尿病相關併發症 腦卒中 (Stroke) 心臟衰竭 (Heart failure) 糖尿病微細血管併發症,T-J WU,0,5,10,15,20,25,30,105,100,95,90,85,80,達成之舒張壓 mm Hg,% 危險性減少,HOT Study 理想的舒張壓,HOT Study 顯示降血壓可降低 心血管意外之危險性達 30%,Hansson et al 1998,0,5,10,15,20,25,90,85,80,mm Hg 目標舒張壓,重大心血管意外 /1000病人/年,Hansson et al 1998,p=0.005 for trend,糖尿病人積極降血壓可有效降低 之心血管意外 (HOT Study),平均舒張壓,基礎腎臟功能與重大心血管意外和舒張壓間之關係,J Hypertens 1999; 17(Suppl 3): S146,0,5,10,15,20,25,30,35,40,75,70,80,85,90,95,100,105,理想舒張壓: High creatinine = 71.9 mmHg Low creatinine = 80.9 mmHg,重大心血管意外 /1000病人/年,Creatinine 1.5 mg/dl,Creatinine 1.5 mg/dl,糖尿病患血壓目標值之實證,Working Group on Hypertension in定140/90 mmHg 為糖尿病患目標血壓 。 JNC VI, 1997 定130/85 mmHg 為糖尿病患目標血壓 。 125/75 mmHg為蛋白尿 ( 1 g/day)病患目標血壓。 UKPDS 與 Hypertension Optimal Treatment (HOT) 研究，兩者皆顯示以血壓130/80mmHg為目標值的治療成效，確實顯著優於較寬鬆目標值的治療。 由流行病學研究資料顯示糖尿病患血壓120/70 mmHg 以上，就與心血管事件以及死亡率增加息息相關。因此，在無特殊安全顧慮下，設定血壓目標值 130/80 mmHg 是合理的。,T-J WU,高血壓病患非藥物治療之實證 (一),減肥 減肥不但可降低血壓、也可改善血糖與血脂肪。每減肥1kg 大約可降低血壓1 mmHg。此作用與鈉攝取量無關。 極低熱量飲食(VLCD) 與藥物治療介入糖尿病患高血壓的角色仍然未充分研究。有些厭食劑可能致血壓升高，反而須要特別注意。 中度限鈉飲食 本態性高血壓患者中度限鈉飲食在降低血壓方面是確有療效的。中度限鈉飲食(每日限鈉由 2.3g) ，本態性高血壓大約可降低縮收舒張血壓5 mmHg，降低舒張血壓2-3 mmHg。 dose response effect” 。 限鈉飲食用於高血壓之糖尿病患族群，雖然廣泛應用，尚待確認。,高血壓病患非藥物治療之實證 (二),體能活動 中度強化體能活動(如：儘可能每天快步 30-45分鐘) 在降低血壓是確有療效的。 35歲或以上病患，執行激烈體能運動計劃時，必須有先行運動壓力測試或其他適當非侵襲性測試 。而一般無症狀病人以中度體能活動 ，一般不須先行運動壓力測試 。 其他建議 JNC 6 建議抽煙必須戒掉；酒須適量。 這些建議也應適用於糖尿病患。,糖尿病之高血壓之大型治療研究,SHEP研究中283位併單獨收縮高血壓之糖尿病患以Diuretic治療之效果,風險減少 (%),Curb JD et al. JAMA. 1996;276:1886-1892.,0,-10,-20,-30,-40,-50,-60,T-J WU,主要CV事件 腦卒中 心肌梗塞 全數死亡率,UKPDS BP Control Study: Tight vs Less Tight Control,Changes in SBP and DBP,80,100,120,140,160,0,1,2,3,4,5,6,7,8,9,Blood pressure (mm Hg),Years from randomization,Systolic blood pressure,Diastolic blood pressure,Less tight,Tight,Less tight control Start 160/94 mm Hg Finish 154/87 mm Hg Tight control Start 161/94 mm Hg Finish 144/82 mm Hg,UKPDS Group. BMJ. 1998;317:703-713.,T-J WU,0.2,Any diabetes-related endpoint 50.9 67.4 Deaths related to diabetes 13.7 20.3 All-cause mortality 22.4 27.2 Myocardial infarction 18.6 23.5 Stroke 6.5 11.6 Peripheral vascular disease 1.4 2.7 Microvascular disease 12.0 19.2,UKPDS BP Control Study: Absolute and Relative Risk,Decreased risk,Increased risk,Less tight control,Tight control,UKPDS Group. BMJ. 1998;317:703-713.,Favors tight control,Favors less tight control,Absolute risk (events per 1000 patient-years),Relative risk* (95% CI),*Vs less tight control.,1,5,Blood pressure (mm Hg),UKPDS BP Control Study: ACE Inhibitor vs -blocker,60,80,100,140,160,180,0,2,4,6,8,Cohort, Mean Values,Years from randomization,Systolic blood pressure,Diastolic blood pressure,There were no differences in BP-lowering efficacy between an ACE inhibitor (captopril) and a -blocker (atenolol).,Less tight control ACE inhibitor -blocker,UKPDS Group. BMJ. 1998;317:713-720.,T-J WU,An ACE inhibitor (captopril) and a -blocker (atenolol) reduced the risk of diabetic complications to a similar extent,*95% CI for all values, except 99% CI for retinopathy and albuminuria; 2-step change.,1.10,1.27,1.14,0.43,0.28,0.44,Any diabetes-related endpoint,Diabetes-related deaths,All-cause mortality,RR,P value,1.20,1.12,1.29,0.35,0.74,0.30,Myocardial infarction,Stroke,Microvascular disease,Retinopathy progression at 7.5 y 0.91 0.28 Urine albumin 50 mg/L at 9 y 1.21 0.31 Urine albumin 300 mg/L at 9 y 0.48 0.09,Relative risk* (95%CI),Favors ACE inhibitor,Favors -blocker,0.5,1,2,UKPDS Group. BMJ. 1998;317:713-720.,UKPDS BP Control Study: ACE Inhibitor vs -Blocker,T-J WU,以血管張力素轉化酵素抑制劑治療高血壓之糖尿病患的效果,風險減少(%),HOPE study investigators. Lancet. 2000;355:253-259.,0,-10,-20,-30,-40,心肌梗塞 腦卒中 CV死亡率 明顯腎病變,T-J WU,Effects of ACEI on BP in Hypertensive Type 2 Diabetics with Incipient Nephropathy BRILLIANT,Agardh C-D, et al. J Hum Hypertens 1996; 10: 185-192,180 160 140 120 100 80,Sittung BP (mmHg),Month of Treatment,0 1 3 6 9 12,Effects of ACEI on Urinary Albumin Excretion in Hypertensive Type 2 Diabetics with Incipient Nephropathy,Agardh C-D, et al. J Hum Hypertens 1996; 10: 185-192,Lisinopril Nifedipine,p0.0006 vs. placebo at 12 months,T-J WU,Albumin Excretion (g/min),Baseline 6 month 12 month,70 60 50 40 30 20 10,BRILLIANT,ACEI Improves Albumin Excretion Rate in Microalbuminuric Patients with T1DM ： EUrodiab Controlled trial of Lisinopril in Insulin dependent Diabetes (EUCLID),EUCLID Study Group. Lancet 1997; 349: 1787-1792,AER (g/min),Time (months),70 60 50 40 30 20 10,6 12 18 24,Placebo Lisinopril,Treatment difference = 38.5g/min, p=0.001,T-J WU,Malaise and fatigue Edema GI tract Diseases Renal Failure Cough Erectile dysfunction Headache Depression Rash Allergic reaction Intermittent claudication Bronchospasm Cold and numb hand Hypokalemia Hyponatremia),Side Effect ACEI CCB Diuretics -blockers No. (%) (n=635) (n=235) (n=283) (n=358),高血壓糖尿病患降血壓治療之主要不良反應,Data Sources: ACEI: ABCD, UKPDS; CCB: ABCD; Diuretics: SHEP; -blockers: UKPDS,TJ WU,21(3.3) 11(1.7) 9(1.4) 6(0.9) 29(4.6) 3(0.5) 2(0.3) 1(0.2) 1(0.2) 7(1.1) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0),0(0.0) 20(8.5) 4(1.7) 2(0.9) 8(3.4) 2(0.9) 10(4.3) 0(0.0) 1(0.4) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 0(0.0),0(0.0) 0(0.0) 0(0.0) 13(4.6) 0(0.0) 34(11.9) 0(0.0) 11(3.9) 0(0.0) 0(0.0) 0(0.0) 0(0.0) 70(24.8) 6(2.3) 22(7.9),16(4.5) 0(0.0) 5(1.4) 0(0.0) 0(0.0) 6(1.7) 3(0.8) 1(0.3) 0(0.0) 2(0.6) 15(4.2) 22(6.2) 0(0.0) 0(0.0) 0(0.0),降血壓藥物對高血壓糖尿病患之影響,Nephroprotective Role of Angiotensin II Receptor Antagonists in Type 2 Diabetes,The Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. The Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL)- were trials conducted in patients with type 2 diabetes with microalbuminuria. These trials demonstrated an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion.,The Effect of Irbesartan on The Development of Diabetic Nephropathy in Patients with T2DM,Onset of Diabetic Nephropathy (%),Relative risk* (95%CI),Favors ARBs,0.5,1,2,10/194,19/195,30/201,300mg/day P0.001,150mg/day P=0.081,Placebo 150mg 300mg /day /day,20 16 12 8 4,Parving HH, et al. N Engl J Med. 2001;345:870-8.,T-J WU,糖尿病病患併高血壓之藥物治療實證 (甲),In patients with either mild or more severe hypertension and in both type 1 and type 2 diabetes, the established practice of choosing an ACE inhibitor as the first-line agent in most patients with diabetes is reasonable. (A) In patients with microalbuminemia or clinical nephropathy, both ACE inhibitors (type 1 and type 2 patients) and ARBs (type 2 patients) are considered first-line therapy for the prevention of and progression of nephropathy. (A) Diuretic and -blockerbased therapy are also supported by evidence (A). DCCBs should be used as second-line drugs. (A) Other classes, including -blockers, may be used under specific indications .,T-J WU,All patients with DM and HTN should be treated with a regimen that includes either an ACEI or ARB. If one class is not tolerated, the other should be substituted. If needed to achieve blood pressure targets, a thiazide diuretic should be added. (E) If ACE inhibitors or ARBs are used, monitor renal function and serum potassium levels. (E) There is clinical trial support for each of the following statements: In patients with type 1 diabetes with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy. (A) In patients with type 2 diabetes, hypertension, and microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria. (A) In those with type 2 diabetes, hypertension, macroalbuminuria (300 mg/day), and renal insufficiency, an ARB should be strongly considered. (A),糖尿病病患併高血壓之藥物治療實證 (乙),T-J WU,0.5,Effects of ARBs on Cardiovascular Events and Renal Disease in T2DM,Siebenhofer A, et al . Diabet Med 2004;21:18-25.,Favors ARBs,Favors Standard,Odds ratio (95% CI),1,2,Total mortality Combined Cardiovasxccular events Combined End-stage renal disease Combined,Lewis Lindholm Lewis Lindholm Lewis,0.5,Favors ARBs,Odds ratio (95% CI),1,2,Favors Placebo,Brenner Lewis Brenner Lewis Brenner Lewis,T-J WU,ARB and Renal Disease in Patients With Type 2 Diabetes An Asian perspective from the RENAAL study,A total of 252 Asian patients were enrolled in the RENAAL study, which compared losartan to placebo in addition to conventional antihypertensive medications in type 2 diabetic patients with nephropathy. Mean follow-up was 3.2 years. Losartan reduced the risk of the primary composite end point composed of a doubling of serum creatinine, end-stage renal disease, or all-cause mortality in Asian patients by 35% (P = 0.02). No difference between losartan and placebo was observed for the cardiovascular composite outcomes. Losartan reduced the level of proteinuria by 47% (P 0.001) and rate of decrease in renal function by 31% (P = 0.0074).,Chan JC, et al Diabetes Care 2004:27:874-879.,超高或高 危險層級,低危險層級,監測血壓與 危險因素 3-6個月,監測血壓與 危險因素 6-12個月,立即藥物治療,收縮壓140或 舒張壓90 開始藥物治療,收縮壓150或 舒張壓95 開始藥物治療,未超出則 繼續監測,未超出則 繼續監測,高血壓處理對策,生活型態調整 : 戒煙, 減肥, 適酒量, 限鹽, 運動等 依危險因子, 靶器官受損, 與關聯狀況評估危險層級,1999 WHO-ISH HYPERTENSION PRACTICE GUIDELINES FOR PRIMARY CARE PHYSICIANS,Classification and Management of BP for adults (JNC7),*Treatment determined by highest BP category. Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. Treat patients with chronic kidney disease or diabetes to BP goal of 130/80 mmHg.,Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range. Those with SBP 120139 mmHg or DBP 8089 mmHg should be considered prehypertensive. Thiazide-type diuretics should be initial drug therapy for most, eithe