Mineralocorticoid Receptor Blockade Improves Coronary Microvascular Function in Individuals With Type 2 Diabetes
Article Figures & Tables
Figures
- Figure 1
An ANCOVA model predicting the change with treatment in CFR. Spironolactone treatment improved CFR as compared with HCTZ (*P = 0.02), placebo (†P = 0.05), and combined HCTZ/placebo groups (‡P = 0.01). HCTZ and placebo had similar effects on CFR (P = 0.79). The predicted adjusted change (95% CI) in posttreatment CFR was 0.38 (0.11, 0.65) with spironolactone, −0.10 (−0.38, 0.18) with HCTZ, and −0.05 (−0.38, 0.28) with placebo. Model adjusts for race, statin use, baseline CFR, and the change in BMI over the treatment period.
Tables
- Table 1
Characteristics of study population at baseline assessment
Spironolactone group HCTZ group Placebo group n 23 24 17 Mean age (years) 56 ± 6 53 ± 7 55 ± 10 Male (n [%]) 17 (74) 13 (54) 10 (59) Race (n [%]) Caucasian 17 (74) 17 (71) 8 (47) African American 4 (17) 6 (25) 7 (41) Other 2 (9) 1 (4) 2 (12) BMI (kg/m2) 31.4 ± 4.5 32.5 ± 5.4 31.3 ± 4.2 BP (mmHg) Systolic 123 ± 11 124 ± 14 125 ± 13 Diastolic 75 ± 7 74 ± 9 77 ± 10 Duration of diabetes (years) 9 ± 7 7 ± 6 7 ± 6 Diabetes medications (n [%]) Metformin 16 (70) 20 (83) 16 (94) Insulin 3 (13) 3 (13) 3 (18) Sulfonylurea 7 (30) 7 (29) 7 (41) Thiazolidinedione 1 (4) 1 (4) 0 (0) GLP-1 analog 1 (4) 1 (4) 2 (12) Dipeptidyl peptidase-4 inhibitor 1 (4) 0 (0) 0 (0) Antihypertensive medications (n [%]) Enalapril 23 (100) 24 (100) 17 (100) Amlodipine 7 (30) 6 (25) 4 (24) Statin use (n [%]) 17 (74) 20 (83) 11 (65) Fasting laboratory data Blood glucose (mg/dL) 105 ± 23 106 ± 25 105 ± 24 Total cholesterol (mg/dL) 150 ± 35 153 ± 24 139 ± 24 LDL cholesterol (mg/dL) 81 ± 27 82 ± 20 75 ± 21 HDL cholesterol (mg/dL) 47 ± 12 45 ± 12 41 ± 12 Triglycerides (mg/dL) 113 ± 39 130 ± 77 120 ± 72 HbA1c (%) 6.6 ± 0.4 7.0 ± 0.9 7.0 ± 0.7 Serum sodium (mmol/L) 139.5 ± 2.1 139.0 ± 2.1 139.2 ± 1.5 Serum potassium (mmol/L) 4.2 ± 0.3 4.3 ± 0.3 4.2 ± 0.2 Creatinine clearance rate (mL/min) 129 ± 30 126 ± 26 124 ± 38 Plasma renin activity (ng/mL/h) 1.5 ± 2.2 2.3 ± 3.3 2.4 ± 3.9 Serum angiotensin II (pg/mL) 18.01 ± 8.89 22.59 ± 6.17 19.15 ± 5.82 Serum aldosterone (ng/dL) 3.13 ± 1.46 3.21 ± 1.19 3.84 ± 2.14 Echocardiography Mitral inflow E (m/s) 0.76 ± 0.14 0.74 ± 0.14 0.68 ± 0.13 A (m/s) 0.68 ± 0.17 0.66 ± 0.16 0.67 ± 0.17 Deceleration time (ms) 220.38 ± 37.94 212.04 ± 37.36 216.88 ± 31.75 E/A ratio 1.15 ± 0.23 1.13 ± 0.29 1.05 ± 0.23 Tissue Doppler imaging e’ (m/s) 0.11 ± 0.02 0.11 ± 0.03 0.11 ± 0.02 E/e’ ratio 7.24 ± 2.00 6.92 ± 1.59 6.58 ± 1.68 Cardiac MRI LV mass index (g/m2) 46.4 ± 12.2 43.6 ± 10.9 46.7 ± 11.2 LV ejection fraction (%) 61.4 ± 4.5 60.2 ± 7.0 60.4 ± 5.0 Myocardial extracellular volume 0.36 ± 0.06 0.34 ± 0.04 0.38 ± 0.04 24-h Urine results Sodium (mmol/24 h) 291 ± 74 258 ± 72 256 ± 77 Creatinine (mg/24 h) 1,599.7 ± 407.5 1,510.4 ± 326.9 1,537.8 ± 466.1 Potassium (mmol/24 h) 97.8 ± 15.0 91.1 ± 19.1 88.8 ± 29.1 Aldosterone (μg/24 h) 6.49 ± 6.46 7.19 ± 5.16 6.17 ± 4.99 Data are expressed as mean ± SD unless stated otherwise. There were no significant differences between treatment groups prerandomization.
- Table 2
Change in study parameter with treatment†
Spironolactone group HCTZ group Placebo group P value spiro vs. HCTZ P value spiro vs. HCTZ + placebo n 23 24 17 Δ BMI (kg/m2) 0.07 ± 0.9 −0.06 ± 1.02 −0.11 ± 1.25 0.59 0.59 Δ BP (mmHg) Systolic −7 ± 13* −5 ± 10* −1 ± 12 0.56 0.25 Diastolic −5 ± 7‡ −2 ± 7 −2 ± 7 0.07 0.09 Δ Fasting laboratory data Glucose (mg/dL) 10.5 ± 23.9 8.3 ± 25.1 2.7 ± 11.8 0.99 0.52 Total cholesterol (mg/dL) 3.6 ± 32.1 2.4 ± 30.2 13.8 ± 32.5 0.24 0.12 LDL cholesterol (mg/dL) 2.9 ± 25.4 1.6 ± 25.2 9.7 ± 30.3 0.46 0.36 HDL cholesterol (mg/dL) −2.0 ± 5.6 1.6 ± 5.0 2.8 ± 6.1 0.05 0.01 Triglycerides (mg/dL) 13.4 ± 37.7 1.9 ± 46.9 11.8 ± 48.3 0.74 0.65 HbA1c (%) 0.16 ± 0.39 0.08 ± 0.75 0.06 ± 0.45 0.94 0.64 Serum sodium (mmol/L) −1.5 ± 2.6 −0.3 ± 2.1 0.0 ± 2.8 0.09 0.04 Serum potassium (mmol/L) 0.22 ± 0.3† 0.03 ± 0.3 0.04 ± 0.2 0.02 0.005 Δ 24-h Urine sodium (mmol/24 h) −19.6 ± 76.9 3.9 ± 78.5 16.5 ± 71.3 0.31 0.15 Δ Creatinine clearance (mL/min) −2.6 ± 21.4 −1.0 ± 20.4 −0.8 ± 13.0 0.96 0.98 Cardiac MRI Δ LV mass index (g/m2) 6.03 ± 22.50 4.81 ± 26.24 8.00 ± 24.05 1.00 0.91 Δ LV ejection fraction (%) −0.87 ± 5.83 0.32 ± 8.25 1.08 ± 5.20 0.22 0.16 Δ Extracellular volume 0.00 ± 0.08 0.00 ± 0.04 0.00 ± 0.03 0.64 0.94 Echocardiography Mitral inflow Δ E (m/s) −0.03 ± 0.15 −0.02 ± 0.09 0.01 ± 0.09 0.87 0.66 Δ A (m/s) −0.02 ± 0.12 −0.02 ± 0.11 −0.01 ± 0.12 0.84 0.88 Δ Deceleration time (ms) −17.93 ± 60.90 8.18 ± 61.24 7.56 ± 57.34 0.49 0.53 Δ E/A ratio −0.02 ± 0.32 0.02 ± 0.18 0.04 ± 0.21 0.75 0.58 Tissue Doppler imaging Δ e’ (m/s) −0.01 ± 0.02 0.00 ± 0.02 0.00 ± 0.01 0.45 0.47 Secondary outcome Δ E/e’ ratio 0.02 ± 1.61 0.06 ± 1.35 0.64 ± 1.95 0.65 0.85 †Posttreatment study parameter minus baseline study parameter.
*P < 0.05, indicates significant change from baseline within treatment group.
‡P < 0.01, indicates significant change from baseline within treatment group. spiro, spironolactone.
- Table 3
Cardiac PET imaging parameters
Characteristic Spironolactone group HCTZ group Placebo group P value spiro vs. HCTZ P value spiro vs. HCTZ + placebo n 22 22 16 Primary outcome Change in global CFR (posttreatment minus baseline)* 0.33 ± 0.83 −0.10 ± 0.65 0.02 ± 1.03 0.04 0.05 Additional measures Change in rest global MBF (mL ⋅ g−1 ⋅ min−1)* −0.07 ± 0.16 0.01 ± 0.11 −0.07 ± 0.13 0.14 0.46 Change in stress global MBF (mL ⋅ g−1 ⋅ min−1)* 0.06 ± 0.46 −0.02 ± 0.34 −0.08 ± 0.57 0.75 0.54 Prerandomization Global CFR 2.77 ± 0.82 2.92 ± 0.52 2.68 ± 0.93 Rest global MBF (mL ⋅ g−1 ⋅ min−1) 0.78 ± 0.23 0.70 ± 0.13 0.73 ± 0.20 Stress global MBF (mL ⋅ g−1 ⋅ min−1) 2.03 ± 0.38 2.00 ± 0.37 1.81 ± 0.40 Posttreatment Global CFR 3.10 ± 1.04 2.83 ± 0.55 2.69 ± 0.96 Rest global MBF (mL ⋅ g−1 ⋅ min−1) 0.72 ± 0.20 0.71 ± 0.11 0.66 ± 0.17 Stress global MBF (mL ⋅ g−1 ⋅ min−1) 2.09 ± 0.50 1.98 ± 0.41 1.73 ± 0.61 *Posttreatment study parameter minus baseline study parameter. spiro, spironolactone.
In this Issue
January 2015, 64(1)
Mineralocorticoid Receptor Blockade Improves Coronary Microvascular Function in Individuals With Type 2 Diabetes
