Mitchell H C, Smith R D, Cutler R E, Sica D, Videen J, Thompsen-Bell S, Jones K, Bradley-Guidry C, Toto R D
Department of Internal Medicine, University of Texas Southwestern at Dallas 75235-8856, USA.
Am J Kidney Dis. 1997 Jun;29(6):897-906. doi: 10.1016/s0272-6386(97)90464-9.
This study was undertaken to compare the effects of chronic angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics in older black and nonblack hypertensive patients with chronic renal insufficiency. A multicenter, placebo lead-in double-blind, parallel group study was performed to compare the antihypertensive efficacy and renal hemodynamic response to the once-daily ACE inhibitor fosinopril (n = 14) and lisinopril (n = 13) over a 22-week period. The study goal was to lower diastolic blood pressure (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure goal was not achieved. At outpatient clinics at university medical centers, 27 older hypertensive patients (> or = 45 years; 12 blacks, 15 nonblacks; 19 male, eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20 to 70 mL/min/1.73 m2 were studied. Changes (delta) from baseline in BP, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean systolic blood pressure (SBP) and DBP decreased significantly and to a similar extent in randomized groups: fosinopril (mean +/- SEM) delta DBP at 6 weeks was -13 +/- 2 (P < 0.0001; 95% CI, -16 to -9) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -9); lisinopril delta DBP at 6 weeks was -14 +/- 6 (P < 0.0001; 95% CI, -10 to -18) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -12 to -21). GFR and RPF did not change significantly in either group. BP was significantly reduced and to a similar extent in blacks and nonblacks: for blacks, delta DBP at 6 weeks was -11 +/- 3 (P < 0.05; 95% CI, -0.01 to -9) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -11 to -20); for nonblacks, delta DBP at 6 weeks was -14 +/- 1 (P < 0.0001; 95% CI, -12 to -17) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -8). Eight patients (five blacks and three nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal of < or = 90 mm Hg at 22 weeks. GFR was not significantly altered for either racial group at 6 weeks; however, at 22 weeks; however, at 22 weeks, GFR decreased significantly in blacks (delta GFR, -16 +/- 5; P < 0.006; 95% CI, -26 to -5) and tended to increase in nonblacks (delta GFR, 7 +/- 6; P > 0.25). delta GFR correlated directly with the delta RPF (delta GFR = 0.0611* delta RPF -2.35 +; r = 0.68; P < 0.003). There was no correlation between delta MAP and delta GFR or delta RPF in blacks or nonblacks. We conclude that chronic ACE inhibition with fosinopril and lisinopril alone or in combination with furosemide lowers BP in older blacks and nonblacks with hypertension and chronic renal insufficiency. Racial differences in the renal hemodynamic response to chronic ACE inhibition were noted and appear to be independent of diuretic use and the magnitude of BP lowering.
本研究旨在比较慢性血管紧张素转换酶(ACE)抑制对老年黑人和非黑人慢性肾功能不全高血压患者血压(BP)及肾脏血流动力学的影响。进行了一项多中心、安慰剂导入双盲、平行组研究,以比较每日一次的ACE抑制剂福辛普利(n = 14)和赖诺普利(n = 13)在22周期间的降压疗效及肾脏血流动力学反应。研究目标是将舒张压(DBP)降至90 mmHg或更低。如果6周后未达到血压目标,则加用呋塞米。在大学医学中心的门诊诊所,对27例年龄较大的高血压患者(≥45岁;12例黑人,15例非黑人;19例男性,8例女性)进行了研究,这些患者的DBP为95 mmHg或更高,4小时肌酐清除率为20至70 mL/min/1.73 m²。测量了血压、肾小球滤过率(GFR)和肾血浆流量(RPF)相对于基线的变化(δ)。随机分组中平均收缩压(SBP)和DBP显著降低且程度相似:福辛普利组6周时δDBP为-13±2(P < 0.0001;95% CI,-16至-9),22周时为-12±2(P < 0.0001;95% CI,-16至-9);赖诺普利组6周时δDBP为-14±6(P < 0.0001;95% CI,-10至-18),22周时为-16±2(P < 0.0001;95% CI,-12至-21)。两组的GFR和RPF均无显著变化。黑人和非黑人的血压均显著降低且程度相似:黑人6周时δDBP为-11±3(P < 0.05;95% CI,-0.01至-9),22周时为-16±2(P < 0.0001;95% CI,-11至-20);非黑人6周时δDBP为-14±1(P < 0.0001;95% CI,-12至-17),22周时为-12±2(P < 0.0001;95% CI,-16至-8)。8例患者(5例黑人,3例非黑人)在6周后需要加用呋塞米以在22周时达到DBP≤90 mmHg的目标。6周时两个种族组的GFR均无显著改变;然而,在22周时,黑人的GFR显著降低(δGFR,-16±5;P < 0.006;95% CI,-26至-5),非黑人则有升高趋势(δGFR,7±6;P > 0.25)。δGFR与δRPF直接相关(δGFR = 0.0611×δRPF - 2.35+;r = 0.68;P < 0.003)。黑人或非黑人中δ平均动脉压(MAP)与δGFR或δRPF之间无相关性。我们得出结论,单用福辛普利和赖诺普利或与呋塞米联合使用进行慢性ACE抑制可降低老年黑人和非黑人高血压及慢性肾功能不全患者的血压。注意到慢性ACE抑制对肾脏血流动力学反应存在种族差异,且似乎与利尿剂使用及血压降低幅度无关。