Angiotensinogen and Risk of Stroke Events in Patients with Type 2 Diabetes Mellitus

Figures & data

Table 1 Clinical Characteristics in 467 Patients with Type 2 Diabetes at Baseline

Variables	eGFR≥57 mL/min/1.73 m^2 (n=233)	eGFR<57 mL/min/1.73 m^2 (n=234)	P value
Age (years)	61.8±7.5	62.4±7.6	0.144
Gender (male), n (%)	110 (47.2)	123 (52.6)	0.219
BMI (kg/m^2)	22.5±6.1	23.1±7.0	0.102
Ever smoker, n (%)	101 (43.3)	112 (47.9)	0.048
Ever drinker, n (%)	107 (45.5)	125 (53.4)	0.042
Duration of diabetes (years)	10±6	15±8	<0.001
Systolic blood pressure (mmHg)	137±14	147±18	<0.001
Diastolic blood pressure (mmHg)	79±8	83±10	<0.001
Taking RAS inhibitors, n (%)	35 (15.0)	87 (37.2)	<0.001
Stroke events during follow-up, n (%)	15 (6.4)	32 (13.7)	0.011
CVD history
Hypertension, n (%)	67 (28.8)	95 (40.6)	0.010
Coronary heart disease, n (%)	11 (4.7)	34 (14.5)	<0.001
Heart failure, n (%)	8 (3.4)	17 (7.3)	0.047
Others, n (%)	4 (1.7)	6 (2.5)	0.098
Laboratory measurements
Log-transformed values of angiotensinogen	23.5±4.1	23.6±4.4	0.719
Log-transformed values of urinary angiotensinogen	1.3±0.4	2.1±0.7	<0.001
HDL (mmol/L)	1.3±0.3	1.2±0.2	0.059
LDL (mmol/L)	2.2±1.1	2.7±1.3	<0.001
ALB (g/L)	37.4 ±6.2	34.2 ±4.6	<0.001
Hb (g/L)	122±10	113±8	0.008
HbA1c (%)	7.2±0.4	7.9±0.5	<0.001
Hs-CRP (pg/mL)	7.1 (3.4–10.2)	9.4 (4.9–14.7)	<0.001

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; RAS, renin-angiotensin system; CVD, cardiovascular disease; HDL, high density lipoprotein; LDL, low density lipoprotein; ALB, albumin; Hb, hemoglobin; HbA1c, glycosylated hemoglobin; hs-CRP, hs-Creactive protein.

Table 2 Cox Proportional Hazard Analysis for the Association Between Urinary and Serum Angiotensinogen Levels and Stroke Events in Patients with Type 2 Diabetes

Variables	Model 1	Model 2	Model 3
Log-transformed values of angiotensinogen, increased 1 SD	1.54 (1.10–3.27)	1.50 (1.04–3.02)	1.42 (0.95–2.65)
P value	0.037	0.049	0.071
Log-transformed values of urinary angiotensinogen, increased 1 SD	2.78 (1.54–5.94)	2.75 (1.51–5.89)	2.74 (1.50–5.88)
P value	<0.001	<0.001	<0.001

Notes: Model 1: adjusted for age, gender, BMI, ever smoker and ever drinker. Model 2: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure and CVD history. Model 3: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history and laboratory measurements.

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; SD, standard deviation.

Figure 1 Kaplan–Meier analysis of the endpoint-free curve stratified into 2 groups by median level of the eGFR.

Table 3 Sensitivity Analysis for the Association Between Urinary and Serum Angiotensinogen Levels and Stroke Events in Patients with Type 2 Diabetes

Variables	Model 1	Model 2	Model 3
Log-transformed values of angiotensinogen, increased 1 SD	1.43 (1.09–3.16)	1.40 (0.94–2.71)	1.37 (0.89–2.21)
P value	0.047	0.069	0.104
Log-transformed values of urinary angiotensinogen, increased 1 SD	2.74 (1.52–5.90)	2.72 (1.50–5.84)	2.71 (1.48–5.82)
P value	<0.001	<0.001	<0.001

Notes: Model 1: adjusted for age, gender, BMI, ever smoker, ever drinker and duration of diabetes. Model 2: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history and duration of diabetes. Model 3: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history, laboratory measurements and duration of diabetes.

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; SD, standard deviation.

Table 4 Stratified Analysis for the Association Between Urinary and Serum Angiotensinogen Levels and Stroke Events in Patients with Type 2 Diabetes by “Taking RAS Inhibitors”

Variables	Model 1	Model 2	Model 3
With taking RAS inhibitors
Log-transformed values of angiotensinogen, increased 1 SD	1.42 (1.08–3.14)	1.38 (0.92–2.68)	1.35 (0.86–2.20)
P value	0.049	0.071	0.132
Log-transformed values of urinary angiotensinogen, increased 1 SD	2.70 (1.51–5.84)	2.67 (1.47–5.80)	2.64 (1.45–5.78)
P value	<0.001	<0.001	<0.001
Without taking RAS inhibitors
Log-transformed values of angiotensinogen, increased 1 SD	1.44 (1.09–3.19)	1.43 (0.96–2.77)	1.37 (0.93–2.25)
P value	0.046	0.065	0.100
Log-transformed values of urinary angiotensinogen, increased 1 SD	2.77 (1.57–6.12)	2.76 (1.58–6.05)	2.74 (1.60–6.01)
P value	<0.001	<0.001	<0.001

Notes: Model 1: adjusted for age, gender, BMI, ever smoker, ever drinker and duration of diabetes. Model 2: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history and duration of diabetes. Model 3: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history, laboratory measurements and duration of diabetes.

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; SD, standard deviation.

Table 5 Stratified Analysis for the Association Between Urinary and Serum Angiotensinogen Levels and Stroke Events in Patients with Type 2 Diabetes by “Egfr≥60 mL/Min/1.73 M²”

Variables	Model 1	Model 2	Model 3
eGFR≥60 mL/min/1.73 m^2
Log-transformed values of angiotensinogen, increased 1 SD	1.43 (1.07–3.12)	1.40 (0.94–2.72)	1.38 (0.90–2.31)
P value	0.049	0.070	0.129
Log-transformed values of urinary angiotensinogen, increased 1 SD	1.51 (1.11–4.21)	1.46 (1.01–3.82)	1.39 (0.95–3.53)
P value	0.034	0.045	0.054
eGFR<60 mL/min/1.73 m^2
Log-transformed values of angiotensinogen, increased 1 SD	1.47 (1.11–3.34)	1.46 (0.97–2.89)	1.43 (0.99–2.36)
P value	0.042	0.063	0.097
Log-transformed values of urinary angiotensinogen, increased 1 SD	2.82 (1.63–6.43)	2.80 (1.61–6.39)	2.78 (1.59–6.30)
P value	<0.001	<0.001	<0.001

Notes: Model 1: adjusted for age, gender, BMI, ever smoker, ever drinker and duration of diabetes. Model 2: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history and duration of diabetes. Model 3: adjusted for age, gender, BMI, ever smoker, ever drinker, systolic and diastolic blood pressure, CVD history, laboratory measurements and duration of diabetes.

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; SD, standard deviation.