3.1 Demographic characteristics and comparison of renal, heart function between the HDP and control groups

There were no significant differences in age, height, weight, BMI, and fast blood glucose between the control group and the HDP group (all p > .05). Both the SBP and the DBP of the HDP group were significantly higher than those of the control group (p < .001 each). The LDL-c, TC, and TG levels of the HDP group were increased, but the HDL-c level was lower (p < .05). The creatinine and urine protein levels were significantly increased in the HDP group, while the eGFR level in the HDP group was lower than that in the control group (p < .05 each). Regarding the results of the echocardiography, compared with the control group, the HDP group showed larger LAD, LAVI, left ventricular posterior wall thickness (LVPWT), and left ventricular septal thickness (LVST) (p < .001 each). There were no significant differences in the left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) (p > .05 each) (Table 1).

TABLE 1. Characteristics of the study population and comparison of renal, cardiac function between the HDP and control group Parameter Control group HDP group p-value Age (year) 31.31 ± 4.037 30.90 ± 3.982 .577 Height (cm) 162.8 ± 4.829 162.3 ± 5.048 .556 Weight (kg) 66.93 ± 9.841 69.53 ± 14.65 .275 BMI (kg/m2) 25.30 ± 3.850 26.33 ± 5.047 .229 SBP (mm Hg) 115.6 ± 8.010 161.4 ± 22.27 < .001* DBP (mm Hg) 74.8 ± 7.458 102.9 ± 14.72 < .001* Glu (mmol/L) 4.37 ± 0.814 4.50 ± 0.829 .379 TC (mmol/L) 6.103 ± 0.898 6.782 ± 1.833 .017* TG (mmol/L) 3.237 ± 1.238 3.755 ± 1.864 .093 LDL-C (mmol/L) 3.05 (2.64, 3.43) 3.815 (3.018, 4.563) < .001* HDL-C (mmol/L) 1.880 (1.625, 2.210) 1.690 (1.400, 2.010) .041* Creatinine (mmol/L) 45.82 ± 8.671 55.15 ± 12.15 < .001* eGFR (ml/min/1.73m2) 128.9 ± 9.848 118.8 ± 14.33 < .001* Urine protein (n, %) − (30, 61.2%) − (0, 0) < .001* −/+ (5, 10.2%) −/+ (8, 10.3%) + (13, 26.5%) + (26, 33.3%) ++ (1, 2.1%) ++ (20, 25.6%) +++ (0, 0) +++ (22, 28.2%) ++++ (0, 0) ++++ (2, 2.6%) LAD (mm) 33.43 ± 3.279 35.73 ± 3.670 < .001* LVEDD (mm) 44.04 ± 3.764 45.19 ± 5.152 .178 LVST (mm) 9.347 ± 1.128 10.24 ± 1.175 < .001* LVPWT (mm) 9.224 ± 1.046 10.0 ± 1.128 < .001* LAVI (ml/m2) 17.60 ± 4.537 21.58 ± 7.058 < .001* LVEF (%) 57.18 ± 2.108 56.95 ± 2.643 .600 Abbreviations: BMI, body mass index; HDP, hypertensive disorders of pregnancy; SBP, systolic blood pressure; DBP, diastolic blood pressure; Glu, glucose; TC, total cholesterol; TG, total triglyceride; LDL-C, low density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; eGFR, estimated glomerular filtration rate; LAD, left atrial diameter; LVEDD, left ventricular end diastolic diameter; LVST, left ventricular septal thickness; LVPWT, left ventricular posterior wall thickness; LAVI, left atrial volume index; LVEF, left ventricular ejection fraction. Values are means ± SDs. 3.2 Comparison of plasma NT-proANP, corin, and sFlt-1/PlGF ratio between the two groups

The NT-proANP and corin in the HDP group were significantly increased compared with the control group (2.364 ± 0.887 vs. 1.489 ± 1.213 nmol/L, p = .001; 2379 ± 786.531 vs. 1341 ± 560.132 pg/ml p < .001). The sFlt-1/PlGF ratio of the HDP group was significantly increased than that of the control group (1.355 [0.865–2.126] vs. 0.765 [0.577–1.103], p < .001) (Figure 2).

Comparison of the plasma NT-proANP, corin, and sFlt-1/PlGF ratio between the two groups. (A) Plasma concentration of NT-proANP. (B) Plasma concentration of corin. (C) Plasma concentration of sFlt-1/PlGF-Ratio. HDP, hypertensive disorders of pregnancy; NT-proANP, N-terminal pro-atrial natriuretic peptide; sFlt-1/PlGF, serum soluble tyrosine kinase-1/placental growth factor

3.3 Correlation of NT-proANP, corin, and sFlt-1/PlGF ratio with target organ dysfunction

In the HDP group, the corin levels were positively correlated with creatinine (r = 0.353, p = .020), while negatively correlated with eGFR (r = -0.394, p = .009). The NT-proANP levels were significantly positively correlated with urine protein (r = 0.337, p = .036), and positively correlated with LAD (r = 0.387, p = .010). There was no significant correlation between the sFlt-1/PlGF ratio and eGFR, urine protein, creatinine, and LAD (all p > .05) (Table 2). In the control group, the NT-proANP, corin levels and sFlt-1/PlGF ratio were not significantly correlated with creatinine, urine protein, eGFR and LAD (all p > .05) (Table S1).

TABLE 2. Correlation of NT-proANP, corin, and sFlt-1/PlGF ratio with creatinine, urine protein, eGFR and LAD in the HDP group NT-proANP (nmol/L) Corin (pg/ml) sFlt-1/PlGF ratio r p-value r p-value r p-value Creatinine (mmol/L) 0.124 .430 0.353 .020* −0.151 .334 Urine protein 0.337 .036* 0.131 .426 −0.248 .128 eGFR (ml/min/1.73m2) −0.160 .307 −0.394 .009* 0.201 .197 LAD (mm) 0.387 .010* 0.280 .069 0.064 .684 Abbreviations: NT-proANP, N-terminal pro-atrial natriuretic peptide; sFlt-1/PlGF, serum soluble tyrosine kinase-1/placental growth factor; LAD, left atrial diameter; eGFR, estimated glomerular filtration rate. *P < 0.05.

Stepwise multiple linear regression was used for analysis in the HDP group with creatinine, eGFR, LAD, LVEDD, LVST, LVPWT, LVEF, and LAVI as dependent variables, meanwhile age, height, weight, SBP, DBP, fast blood glucose, TC, TG, LDL-c, HDL-c, NT-proANP, corin, and sFlt-1/PlGF ratio as independent variables. Stepwise multiple linear regression showed that Corin was an independent predictor for creatinine and eGFR in the HDP group. NT-proANP was an independent predictor for LAD (Table 3). Logistic regression analysis of urine protein in hypertensive disorders of pregnancy patients with age, height, weight, SBP, DBP, fast blood glucose, TC, TG, LDL-c, HDL-c, NT-proANP, corin, and sFlt-1/PlGF ratio were used as independent variables. Multivariate logistic regression analysis showed that NT-proANP was a significant predictor of urine protein (OR: 5.474, 95% CI: 1.147-26.119, p = .033) (Table S2).

TABLE 3. Stepwise multiple linear regression analysis of creatinine, eGFR, LAD, LVEDD, LVST, LVPWT, LVEF, and LAVI in HDP patients Independent variables β-coefficient t-value p value Creatinine Corin 0.353 2.414 .020 eGFR Age −0.472 −3.744 .001 Corin −0.334 −2.646 .012 LAD SBP −0.346 −2.506 .016 NT-proANP 0.321 2.321 .025 LVEDD SBP 0.538 4.088 < .001 LVST SBP 0.699 6.260 < .001 LVPWT SBP 0.500 3.695 .001 LVEF (%) SBP −0.463 −3.345 .002 LAVI Height −0.420 −3.023 .004 Weight −0.318 −2.285 .028 DBP 0.394 3.090 .004 Abbreviations: eGFR, estimated glomerular filtration rate; LAD, left atrial diameter; LVEDD, left ventricular end diastolic diameter; LVST, left ventricular septal thickness; LVPWT, left ventricular posterior wall thickness; LVEF, left ventricular ejection fraction; LAVI, left atrial volume index; NT-proANP, N-terminal pro-atrial natriuretic peptide. 3.4 Comparison of ROC curves of NT-proANP, corin, and sFlt-1/PlGF ratio in pregnancy with or without hypertension

The sensitivity and specificity of NT-proANP at a cut-off value of 151.1 nmol/L were 81.4% and 76.9%, with an AUC of 0.779 (95% CI, 0.644–0.914). The sensitivity and specificity of corin at a cut-off value of 1891.8 pg/ml were 69.8% and 88.5%, with an AUC of 0.867 (95% CI, 0.778–0.955). The sensitivity and specificity of sFlt-1/PlGF ratio at a cut-off value of 138.6 were 48.8% and 96.2%, with an AUC of 0.766 (95% CI, 0.656–0.875) (Figure 3 and Table 4). The corin showed better predictive ability compared with the sFlt-1/PlGF ratio (p < .001), however, there was no statistical significant difference between NT-proANP and sFlt-1/PlGF ratio (p = .660).

ROC curves for predicting the severity of pregnant women with or without hypertension. Blue line: NT-proANP; Red line: Corin; Green line: sFlt-1/PLGF ratio; NT-proANP, N-terminal pro-atrial natriuretic peptide; sFlt-1/PlGF, serum soluble tyrosine kinase-1/placental growth factor

TABLE 4. Comparison of ROC curve in the HDP and control group AUC (95%-CI) Threshold Sensitivity (%) Specificity (%) p-value NT-proANP 0.779 (0.644–0.914) 151.1 81.4 76.9 < .001 Corin 0.867 (0.778–0.955) 1891.8 69.8 88.5 < .001 sFlt-1/PlGF-Ratio 0.766 (0.656–0.875) 138.6 48.8 96.2 < .001 Abbreviations: AUC, Area under the curve; CI, Confidence interval; NT-proANP, N-terminal pro-atrial natriuretic peptide; sFlt-1/PlGF, serum soluble tyrosine kinase-1/placental growth factor.