The incidence and influencing factors of aldosterone escape in PA patients after spironolactone treatment
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摘要: 目的 探讨螺内酯治疗后原发性醛固酮增多症(PA)患者醛固酮逃逸的发生率及影响因素。方法 回顾性分析2021年1月—2023年3月云南省阜外心血管病医院收治的144例PA患者资料，根据螺内酯治疗前后醛固酮浓度变化分为非逃逸组和逃逸组，比较两组患者用药前临床资料，同时分析影响因素。结果 144例PA患者中68例患者发生了醛固酮逃逸，醛固酮逃逸发生率为47.22%。与非逃逸组相比，逃逸组用药前肾功能不全比例更低，血浆醛固酮(立位)、醛固酮(卧位)、尿素氮(BUN)、同型半胱氨酸(HCY)、C反应蛋白(CRP)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)水平及尿微量白蛋白/肌酐更低，差异有统计学意义(均P＜0.05)。单因素logistic回归分析显示，用药前肾功能不全病史、血浆醛固酮(立位)、醛固酮(卧位)、T3、FT3、促甲状腺激素(TSH)水平是PA患者治疗后醛固酮逃逸的影响因素(分别为β=-0.985，OR=0.373，P=0.031；β=-0.063，OR=0.938，P=0.002；β=-0.060，OR=0.942，P=0.014；β=-1.103，OR=0.332，P=0.029；β=-0.631，OR=0.532，P=0.010；β=-0.249，OR=0.780，P=0.044)。多因素logistic回归分析显示，用药前血浆醛固酮(立位)、FT3、TSH水平是PA患者治疗后发生醛固酮逃逸的独立危险因素(分别为β=-0.053，OR=0.949，P=0.031；β=-0.910，OR=0.402，P=0.042；β=-0.379，OR=0.685，P=0.013)。结论 部分PA患者在螺内酯治疗后出现醛固酮逃逸现象，用药前血浆醛固酮(立位)、FT3、TSH水平是该现象的独立危险因素。Abstract: Objective To investigate the incidence and influencing factors of aldosterone escape in patients with primary aldosteronism(PA) after spironolactone treatment.Methods The data of 144 patients with PA admitted to Fuwai Cardiovascular Disease Hospital in Yunnan Province from January 2021 to March 2023 were retrospectively analyzed. According to the changes of aldosterone concentration before and after spironolactone treatment, they were categorized into non-escape group and escape group. The clinical data of the two groups were compared before the administration of spironolactone, and the influencing factors were analyzed at the same time.Results Aldosterone escape occurred in 68 of 144 patients with PA, and the incidence of aldosterone escape was 47.22%. Compared with the non-escape group, the escape group had a lower proportion of pre-dose renal insufficiency, and lower plasma aldosterone(standing), aldosterone(lying), urea nitrogen(BUN), homocysteine(HCY), C-reactive protein(CRP), triiodothyronine(T3), thyroxine(T4), free triiodothyronine(FT3) levels, and urinary microalbumin/creatinine, and the differences were statistically significant(all P < 0.05). One-way logistic regression analysis showed that history of renal insufficiency, plasma aldosterone(standing), aldosterone(lying), T3, FT3, and thyroid-stimulating hormone(TSH) levels prior to medication were correlated with the occurrence of post-treatment aldosterone escape in patients with PA(β=-0.985, OR=0.373, P=0.031; β=-0.063, OR=0.938, P=0.002; β=-0.060, OR=0.942, P=0.014; β=-1.103, OR=0.332, P=0.029; β=-0.631, OR=0.532, P=0.010; β=-0.249, OR=0.780, P=0.044). Multifactorial logistic regression analysis showed that pre-dose plasma aldosterone(standing), FT3, and TSH levels were independent risk factors for the occurrence of aldosterone escape after treatment in PA patients(β=-0.053, OR=0.949, P=0.031; β=-0.910, OR=0.402, P=0.042; β=-0.379, OR=0.685, P=0.013).Conclusion Some patients with PA experienced aldosterone escape after spironolactone treatment, and pre-dose plasma aldosterone(standing), FT3, and TSH levels were independent risk factors for this phenomenon.
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Key words:
- primary aldosteronism /
- spironolactone /
- aldosterone escape
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表 1 两组一般资料比较
Table 1. General data
例(%), X±S 项目 非逃逸组(76例) 逃逸组(68例) χ2/Z/t P 男性 28(36.8) 17(25) 2.343 0.126 年龄/岁 51.08±10.71 53.35±11.31 -1.239 0.218 肾动脉狭窄 5(6.6) 2(2.9) 0.391 0.532 肾功能不全 20(26.3) 8(11.8) 4.851 0.028 高脂血症 57(75) 50(73.5) 0.041 0.840 高尿酸血症 24(31.6) 20(29.4) 0.079 0.778 糖尿病 11(14.5) 13(19.1) 0.557 0.455 甲状腺疾病 24(31.6) 25(36.8) 0.430 0.512 OSAS 54(71.1) 46(67.6) 0.196 0.658 高血压等级 -0.997 0.315 高血压1级 0 1(1.5) 高血压2级 11(14.5) 13(19.1) 高血压3级 65(85.5) 54(79.4) 高血压家族史 49(64.5) 48(70.6) 0.610 0.435 糖尿病家族史 8(10.5) 11(16.2) 1.000 0.317 BMI/(kg/m2) 25.67±3.66 24.77±3.10 1.583 0.116 
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表 2 两组实验室资料比较
Table 2. Comparison of laboratory data between the two groups
X±S, M(P25, P75) 项目 非逃逸组(76例) 逃逸组(68例) Z/t P ALD(立位)/(pg/mL) 26.95(20.43，35.65) 20.10(16.93，24.28) -3.996 0.000 肾素(立位)/(μIU/mL) 3.94(1.76，7.75) 3.90(1.91，6.80) -0.011 0.991 ARR(立位)/(pg/μIU) 6.61(3.64，15.27) 5.46(3.32，10.79) -1.283 0.199 ALD(卧位)/(pg/mL) 20.20±8.90 16.91±5.86 2.644 0.009 肾素(卧位)/(μIU/mL) 1.84(0.94，3.33) 1.71(1.71，3.02) -0.764 0.445 ARR(卧位)/(pg/μIU) 9.32(5.81，17.28) 9.47(5.23，18.61) -0.154 0.878 ALD比值(输液前后) 0.55±0.18 0.57±0.20 -0.552 0.582 肾素比值(输液前后) 0.65(0.50，0.88) 0.70(0.48，0.79) -0.201 0.841 ARR比值(输液前后) 0.97±0.71 0.92±0.42 0.441 0.660 ALD比值(卡托普利前后) 0.75±0.28 0.78±0.25 -0.587 0.558 肾素比值(卡托普利前后) 1.71(1.27，2.45) 1.51(1.08，2.19) -1.141 0.254 ARR比值(卡托普利前后) 0.37(0.27，0.59) 0.48(0.30，0.76) -1.621 0.105 ACTH 8∶00/(pg/mL) 40.02±32.30 32.46±20.78 1.615 0.109 血皮质醇8∶00/(μg/dL) 13.61(10.72，16.53) 11.6(9.06，16.31) -1.785 0.074 ACTH 16∶00/(pg/mL) 18.63±8.33 17.82±9.00 0.551 0.582 血皮质醇16∶00/(μg/dL) 6.49(4.59，8.76) 6.21(5.14，7.24) -0.434 0.664 ACTH 24∶00/(pg/mL) 7.66(5.15，11.5) 8.03(5.33，10.44) -0.163 0.871 血皮质醇24∶00/(μg/dL) 2.17(1.45，3.44) 2.03(1.60，3.16) -0.256 0.798 WBC/(×109/L) 6.14±1.67 5.97±1.48 0.632 0.528 NEUT/% 61.01±8.18 58.69±9.24 1.601 0.112 LYMPH/% 28.96±7.26 30.99±8.54 -1.535 0.127 PT/s 11.21±0.55 11.40±0.62 -1.972 0.051 APTT/s 31.23±2.59 31.06±4.08 0.307 0.759 TT/s 14.46±1.09 14.67±1.02 -1.204 0.231 FIB/(g/L) 3.00±0.57 2.90±0.63 1.002 0.318 D-二聚体/(mg/L) 0.08(0.05，0.13) 0.07(0.05，0.12) -0.963 0.335 NT-proBNP/(ng/L) 54.38(31.18，87.96) 50.8(26.42，90.45) -0.172 0.864 ESR/(mm/h) 5(2，10) 6(2，11) -0.315 0.753 K+/(mmol/L) 4.01(3.77，4.29) 3.97(3.72，4.29) -0.292 0.770 Na+/(mmol/L) 139.09±1.90 139.33±2.52 -0.628 0.531 GLU/(mmol/L) 5.03(4.76，5.40) 5.05(4.74，5.39) -0.231 0.817 BUN/(mmol/L) 5.21±1.31 4.80±1.16 1.980 0.050 Cr/(μmol/L) 71.35(58.48，89.50) 64.4(55.78，79.40) -1.677 0.094 BUA/(μmol/L) 361.41±90.64 353.04±88.46 0.559 0.577 HCY/(μmol/L) 13.5(12.2，15.5) 12.6(11.0，14.45) -1.964 0.049 ASO/(IU/mL) 29.97(14.01，67.92) 34.67(20.2，66.14) -1.068 0.285 CRP/(mg/L) 2.16(1.29，3.67) 1.50(1.02，2.87) -2.035 0.042 RF/(IU/mL) 8.61±21.98 11.44±26.24 -0.670 0.504 IgG/(g/L) 12.17(10.30，14.16) 11.87(10.36，14.98) -0.353 0.724 IgA/(g/L) 1.86(1.53，2.56) 2.14(1.61，2.89) -1.389 0.165 IgM/(g/L) 1.16±0.58 1.33±0.62 -1.618 0.108 TC/(mmol/L) 4.51±1.29 4.57±1.20 -0.291 0.771 TG/(mmol/L) 1.94±1.67 1.59±0.76 1.581 0.116 APOA1/(g/L) 1.29(1.19，1.48) 1.36(1.22，1.52) -1.048 0.295 APOB/(g/L) 0.81±0.25 0.84±0.21 -0.766 0.445 Lp(a)/(mg/dL) 12.02(6.39，30.50) 11.61(5.69，24.70) -0.787 0.431 HDL-C/(mmol/L) 1.19±0.30 1.22±0.26 -0.675 0.501 LDL-C/(mmol/L) 2.73±0.91 2.89±0.79 -1.092 0.276 T3/(nmol/L) 1.74±0.38 1.60±0.35 2.264 0.025 T4/(nmol/L) 100.31±27.12 91.88±21.78 2.017 0.046 FT3/(pmol/L) 4.85±0.67 4.52±0.79 2.677 0.008 FT4/(pmol/L) 16.48±2.94 16.24±3.34 0.453 0.651 TSH/(mIU/L) 2.36(1.34，3.27) 2.01(1.31，2.68) -1.866 0.062 24 h尿钠/钾 2.12(1.38，2.92) 1.69(1.40，2.60) -1.080 0.280 24 h尿ALD含量/nmoL 10.79(8.54，15.36) 11.42(7.78，19.37) -0.259 0.796 24 h尿蛋白定量/mg 70(36，97.5) 67.5(40.38，93.00) -0.327 0.744 尿微量白蛋白/肌酐/(mg/mmoL) 15.08(8.50，40.66) 11.49(6.24，23.57) -2.171 0.030
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表 3 两组心脏超声指标比较
Table 3. Cardiac ultrasound indexes between the two groups
X±S, M(P25, P75) 项目 非逃逸组(76例) 逃逸组(68例) χ2/Z/t P IVST/mm 9(8，10) 10(9，10) -1.404 0.160 LVDd/mm 45.54±3.81 45.25±3.46 0.475 0.635 LVEF/% 66.72±3.81 65.96±4.21 1.139 0.257 LVPWT/mm 9(8，9) 9(8，10) -0.088 0.930
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表 4 用药后发生醛固酮逃逸的单因素logistic回归分析
Table 4. Single factor logistic regression analysis of aldosterone escape
变量 β SE χ2值 P值 OR值 95%CI 肾功能不全 -0.985 0.458 4.633 0.031 0.373 0.152~0.916 ALD(立位) -0.063 0.020 10.041 0.002 0.938 0.904~0.976 ALD(卧位) -0.060 0.024 6.056 0.014 0.942 0.898~0.988 BUN -0.272 0.140 3.752 0.053 0.762 0.579~1.003 HCY -0.10 0.030 0.113 0.737 0.990 0.933~1.050 CRP -0.109 0.075 2.101 0.147 0.897 0.774~1.039 T3 -1.103 0.505 4.771 0.029 0.332 0.123~0.893 T4 -0.016 0.008 3.749 0.053 0.984 0.969~1.000 FT3 -0.631 0.274 6.548 0.010 0.532 0.328~0.863 TSH -0.249 0.124 4.061 0.044 0.780 0.612~0.993 尿微量白蛋白/肌酐 -0.002 0.002 1.759 0.185 0.998 0.994~1.001
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表 5 用药后发生醛固酮逃逸的多因素logistic回归分析
Table 5. Multivariate logistic regression analysis of aldosterone escape
变量 β SE χ2值 P值 OR值 95%CI 肾功能不全 -0.217 0.528 0.169 0.681 0.805 0.286~2.266 ALD(立位) -0.053 0.025 4.653 0.031 0.949 0.904~0.995 ALD(卧位) -0.014 0.034 0.170 0.680 0.986 0.923~1.054 T3 0.274 0.855 0.102 0.749 1.315 0.246~7.030 FT3 -0.910 0.447 4.139 0.042 0.402 0.167~0.967 TSH -0.379 0.152 6.220 0.013 0.685 0.509~0.922 常量 6.217 1.699 13.386 0.000 501.280
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