Background
Methods
Patients, ethics, consent and permissions
Ambulatory blood pressure
Biochemical analyses
Echocardiography
Endothelial function test
Thickness of the carotid artery intima-media (c-IMT)
Pulse wave velocity
Statistical analysis
Results
Patient characteristics at baseline and follow-up
Variable | n(%) |
---|---|
Age (years) | 34.86 ± 9.17 |
Gender (male) | 105(52) |
Hypertension (present) | 70(35.0) |
Smokers | 21(10.3) |
Diabetes(present) | 11(5) |
Receiving oral hypoglycemictherapy | 10(5) |
With cardiovascular comorbidities | 7(3) |
Variable | Reference values | Baseline (n = 202) | Follow-up (n = 202) | ΔChange% |
p
|
---|---|---|---|---|---|
eGFR(ml/min/1.73 m2) | >90 | 69.0(54.0–78.0) | 65.0(44.0–75.0) | −5.80 |
<0.001
|
BMI (kg/m2) | 20–24 | 24.67 ± 2.78 | 24.98 ± 2.47 | 1.26 | 0.212 |
Calcium (mg/dl) | 8.8–10.2 | 8.27 ± 0.45 | 8.19 ± 0.31 | −0.97 |
0.039
|
Sodium (mmol/L) | (135–144) | 139.48 ± 4.22 | 137.59 ± 3.62 | −1.37 | 0.066 |
Phosphorus (mg/dl) | 2.5–4.5 | 4.80(4.13–5.30) | 5.70(4.80–8.20) | 18.75 |
<0.001
|
HDL Cholesterol (mg/dl) | 45–65 | 43(39.0–46.0) | 45.0(40.25–47.00) | 4.65 |
0.003
|
LDL Cholesterol (mg/dl) | 100–130 | 123(118–129) | 128(109–139) | 4.07 |
0.005
|
Total Cholesterol (mg/dl) | 70–200 | 193.71 ± 15.02 | 194.05 ± 16.44 | 0.18 | 0.843 |
Triglyceride (mg/dl) | 40–130 | 140.37 ± 11.41 | 134.46 ± 11.19 | −4.21 |
<0.001
|
Hemoglobin (g/l) | 12–16 | 14.0(12.8–14.7) | 13.6(13.1–14.0) | −2.86 |
0.002
|
Glucose (mg/dl) | 82–115 | 85.0(78–120) | 88(80–115) | 3.53 |
0.001
|
Urine volume (mL) | - | 1868 ± 572 | 1780 ± 568 | −3.71 | <0.001 |
U-osmolarity (mOsm/kg) | - | 205(178–245) | 289(254–395) | 42.85 | <0.001 |
Average 24-h systolic BP, mmHg | <130 | 135 ± 6.9 | 142 ± 7.2 | 5.19 |
<0.001
|
Average 24-h diastolic BP, mmHg | <80 | 83 ± 4.8 | 86 ± 5.3 | 3.61 |
<0.001
|
Proteinuria (mg/day) | 0–150 | 1100 (500–1870) | 1540 (720–2600) | 40.00 |
<0.001
|
Left ventricular ejection fraction(%) | >55 | 64.4 ± 5.0 | 62.1 ± 5.8 | −3.57 | 0.245 |
Left ventricular mass (g) | 49–115 | 169.4 ± 37.3 | 171.3 ± 46.5 | 1.12 | 0.311 |
Left ventricular end-diastolic diameter (mm) | 42–59 | 46.5 ± 2.9 | 47.0 ± 3.4 | 0.88 | 0.175 |
PWV (m/sec) | - | 8.10 ± 1.20 | 8.24 ± 1.34 | 1.73 |
0.044
|
FMD, % | - | 6.92 ± 0.87 | 5.78 ± 0.92 | −16.47 |
<0.001
|
CIMT(mm) | - | 0.72 ± 0.11 | 0.82 ± 0.08 | 13.89 |
<0.001
|
Copeptin (ng/mL) | N/A | 0.62 ± 0.12 | 0.94 ± 0.19 | 51.61 |
<0.001
|
Hs-CRP (mg/l) | <0.2 | 3.40(2.20–4.0) | 9.00(5.10–19.0) | 164.71 |
<0.001
|
Univariate correlations and regression
Variable | S-Copeptin (ng/mL) | Proteinuria (mg/day) | SBP (mmHg) | DBP (mmHg) | U-osmolarity (mOsm/kg) | U-volume (mL) | cIMT (mm) | LVM (g) | LVEDD (mm) | eGFR (ml/min/1.73 m2) |
---|---|---|---|---|---|---|---|---|---|---|
S-Copeptin (ng/mL) | 1.000 | - | - | - | - | - | - | - | - | - |
Proteinuria (mg/day) |
0.346**
| 1.000 | - | - | - | - | - | - | - | - |
SBP (mmHg) |
0.171*
| 0.095 | 1.000 | - | - | - | - | - | - | - |
DBP (mmHg) |
0.216**
|
0.257**
|
0.273**
| 1.000 | - | - | - | - | - | - |
U-osmolarity (mOsm/kg) |
0.430**
| 0.132 | 0.097 | 0.070 | 1.000 | - | - | - | - | - |
U-volume (mL) | −0.030 | −0.036 | −0.102 |
−0.187**
| 0.001 | 1.000 | - | - | - | - |
cIMT (mm) |
0.643**
|
0.268**
| 0.088 |
0.274**
|
0.236**
| −0.028 | 1.000 | - | - | - |
LVM (g) | 0.118 | 0.055 | 0.158 | 0.089 | 0.085 | 0.099 | 0.128 | 1.000 | −0.145 | - |
LVEDD (mm) | −0.069 | 0.142 | 0.094 | 0.166 | 0.022 | 0.128 | 0.056 | 0.133 | 1.000 | - |
eGFR (ml/min/1.73 m2) |
−0.304**
|
−0.386**
|
−0.253**
|
−0.272**
|
−0.204**
| 0.063 |
−0.355**
| −0.162 | 0.137 | 1.000 |
Variable | ΔPWV | ΔFMD | ΔeGFR | Δcopeptin | ΔcIMT | |||||
---|---|---|---|---|---|---|---|---|---|---|
Univariate | Multiple | Univariate | Multiple | Univariate | Multiple | Univariate | Multiple | Univariate | Multiple | |
ΔBMI (kg/m2) | 0.056(0.429) | - | −0.053(0.457) | - | 0.083(0.243) | - | 0.019(0.685) | - | 0.133(0.054) | - |
ΔCalcium (mg/dl) | 0.206(0.003) | - | 0.011(0.881) | - | −0.038(0.595) | - | 0.134(0.200) | - | 0.063(0.420) | - |
ΔPhosphorus (mg/dl) | 0.113(0.112) | - | 0.027(0.708) | - | 0.117(0.100) | - | 0.109(0.150) | - | 0.055(0.460) | - |
ΔHDL Cholesterol (mg/dl) | 0.117(0.099) | - | −0.149(0.035) | −0.175(0.002) | 0.071(0.319) | - | 0.085(0.365) | - | −0.048(0.484) | - |
ΔLDL Cholesterol (mg/dl) | 0.260(<0.001) | - | −0.037(0.604) | - | −0.016(0.827) | - | 0.053(0.460) | - | −0.038(0.594) | - |
ΔTotal Cholesterol (mg/dl) | −0.111(0.118) | - | −0.143(0.044) | - | 0.056(0.432) | - | 0.091(0.332) | −0.056(0.360) | - | |
ΔTriglyceride (mg/dl) | 0.170(0.016) | - | 0.194(0.006) | 0.146 (0.010) | −0.101(0.154) | - | −0.107(0.102) | - | 0.099(0.163) | - |
Δ Hemoglobin (g/l) | −0.008(0.910) | - | −0.030(0.675) | - | 0.081(0.256) | - | 0.080 (0.134) | - | 0.079(0.283) | - |
ΔGlucose (mg/dl) | 0.060(0.398) | - | −0.075(0.293) | - | −0.127(0.073) | - | −0.050 (0.705) | - | 0.117(0.110) | - |
ΔAverage 24-h SBP, mmHg | 0.128(0.026) | 0.249(0.001) | 0.366(0.005) | 0.268(0.017) | −0.429(<0.001) | −0.348(<0.001) | 0.383(<0.001) | - | 0.317(<0.001) | - |
ΔAverage 24-h D BP, mmHg | −0.018(0.799) | - | −0.180(0.011) | - | 0.079(0.263) | - | 0.493(<0.001) | 0.313(<0.001) | 0.385(<0.001) | 0.142(0.030) |
ΔProteinuria (mg/day) | 0.045(0.523) | - | −0.170(0.016) | - | 0.060(0.400) | - | 0.168(0.018) | 0.133(0.018) | 0.168(0.017) | 0.131(0.028) |
Δ CIMT(mm) | 0.138(0.051) | - | −0.302(<0.001) | - | −0.065(0.364) | - | 0.562(<0.001) | 0.347(<0.001) | - | - |
Δ Copeptin (ng/mL) | 0.179(0.011) | 0.267(<0.001) | 0.599(<0.001) | 0.582(<0.001) | −0.414(<0.001) | −0.331(<0.001) | - | - | 0.562(<0.001) | 0.391(<0.001) |
ΔHs-CRP (mg/l) | 0.120(0.034) | - | 0.255(<0.001) | - | −0.182(0.009) | - | 0.378(<0.001) | 0.196(0.001) | 0.372(<0.001) | 0.210(0.001) |
Multivariate modelling
Baseline copeptin as a predictor of future changes
Variable | Area under curve | Diagnostic statistics | |||||
---|---|---|---|---|---|---|---|
AUC |
p
| Co-peptin cut-off used (from ROC) | SEN (%) | SPE (%) | PPV(%) | NPV(%) | |
FMD (> or ≤7.1%) | 0.75(0.68–0.80) | <0.001 | 0.59 ng/mL | 88.0(79.6–93.6) | 57.4(47.5–66.9) | 63.8(54.8–72.1) | 84.9(74.6–92.2) |
PWV (> or ≤7.8 m/sec) | 0.58(0.50–0.65) | 0.064 | 0.76 ng/mL | 51.1(40.4–61.7) | 71.3(61.8–79.6) | 60.8(48.5–71.2) | 63.1(53.9–71.7) |
eGFR(> or ≤59 mL/min/1.73 m2) | 0.61(0.54–0.68) | 0.008 | 0.81 ng/mL | 43.5(33.2–55.2) | 60.2(50.3–60.9) | 52.2(41.4–62.9) | 59.1(49.3–68.4) |
cIMT (> or ≤0.8 mm) | 0.86(0.80–0.90) | <0.001 | 0.58 ng/mL | 79.4(69.6–87.1) | 88.9(81.4–94.1) | 85.9(76.6–92.5) | 83.5(75.4–89.7) |
Variables | ΔFMD | ΔPWV | ΔeGFR | ΔcIMT | ||||
---|---|---|---|---|---|---|---|---|
Univariate OR(95%CI) | Adjusted OR(95%CI) | Univariate OR(95%CI) | Adjusted OR(95%CI) | Univariate OR(95%CI) | Adjusted OR(95%CI) | Univariate OR(95%CI) | Adjusted OR(95%CI) | |
ΔLDL (mg/dl) | −0.109(0.125) | - | −0.179(0.011) | −0.162(0.018) | 0.007(0.925) | - | 0.072(0.311) | - |
ΔAverage 24-h SBP, (mmHg) | −0.167(0.018) | - | 0.015(0.828) | - | 0.112(0.115) | - | 0.017(0.810) | - |
ΔAverage 24-h D BP,(mmHg) | −0.061(0.394) | - | 0.007(0.917) | - | 0.104(0.142) | - | 0.055(0.442) | - |
ΔFMD (%) | - | - | −0.163(0.021) | - | 0.029(0.688) | - | −0.197(0.005) | - |
ΔPWV (m/sec) | −0.106(0.135) | - | - | - | 0.041(0.565) | - | −0.177(0.012) | −0.162(0.009) |
ΔeGFR(ml/min/1.73 m2) | −0.223(0.001) | −0.252(<0.001) | −0.265(<0.001) | −0.253(<0.001) | - | - | −0.448(<0.001) | −0.473(<0.001) |
ΔcIMT (mm) | −0.334(<0.001) | - | −0.024(0.737) | - | −0.188(0.008) | −0.188(0.008) | - | - |
ΔCopeptin (ng/mL) | −0.431(<0.001) | −0.448(<0.001) | 0.014(0.839) | - | −0.109(0.125) | - | −0.238(0.001) | −0.240(<0.001) |