Combined use of brain natriuretic peptide and C-reactive protein for predicting cardiovascular risk in outpatients with type 2 diabetes mellitus

Figures & data

Table 1 Clinical characteristics of the patients (n = 109)

Parameter
Age, y	71 ± 10
Male (%)	50
Body mass index (kg/m2)	24 ± 4
Current smoker (%)	17
Hypertension (%)	77
Hyperlipidemia (%)	53
Atrial fibrillation (%)	6
Valvular diseases (%)	10
History of cardiovascular diesases (N/C/H)	80/13/16
Systolic blood pressure (mmHg)	137 ± 16
Diastolic blood pressure (mmHg)	71 ± 11
Fasting blood glucose (mg/dL)	137 ± 44
Hemoglobin A1c (%)	6.6 ± 1.5
Total cholesterol (mg/dL)	204 ± 35
Triglyceride (mg/dL)	113 [86, 158]
Serum creatinine (mg/dL)	0.8 ± 0.3
Urinary albumin (mg/gCreatinine)	33 [13, 139]
BNP (pg/mL)	26.7 [14.3, 57.2]
CRP (mg/dL)	0.10 [0.04, 0.20]
Sulfonylurea (%)	48
Biguanide (%)	3
α-glycosidase inhibitor (%)	34
thiazolidinedione (%)	6
Glinide (%)	8
ACEI (%)	17
ARB (%)	11
β-blocker (%)	16
Calcium channel blocker (%)	55
Diuretics (%)	9
Aspirin (%)	13
Statin (%)	24

Notes: Data are presented as means ± SD, percentage or median [25, 75 percentiles] of the values.

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin II type 1 receptor blocker; N, C and H indicates none of any past cardiovascular diseases, cerebral infarction/hemorrhage or heart diseases, such as angina pectoris, myocardial infarction and heart failure.

Table 2 Echocardiographic parameters

Size of left atrium (cm)	3.2 ± 0.7
Left ventricular diastolic dimension (cm)	4.2 ± 0.8
Left ventricular systolic dimension (cm)	2.7 ± 0.6
Left ventricular mass (g/m^2)	132 ± 46
Left ventricular ejection fraction (%)	66 ± 10
Ratio of E to A velocity	0.9 ± 0.5
Deceleration time (ms)	211 ± 63

Values are means ± SD

Table 3 Association of BNP or CRP with the other variables

	BNP		CRP
	Spearman CC	p value	Spearman CC	p value
Age	0.445	<0.001	0.049	0.61
BMI	−0.079	0.411	0.370	<0.001
HOMA-R	−0.206	0.033	0.254	0.008
HDL-C	−0.136	0.158	−0.260	0.006
Urinary albumin	0.130	0.18	0.224	0.02
Creatinine	0.306	0.001	0.119	0.219
LA size	0.268	0.006	0.206	0.038
LV mass index	0.330	0.001	0.121	0.23
LVEF	−0.231	0.018	−0.212	0.031

Abbreviations: CC, correlation coefficient; BMI, body mass index; HOMA, homeostasis model assessment; LA, left atrial; LV, left ventricular; EF, ejection fraction.

Table 4 Linear regression analysis for BNP and CRP

Dependent variable	Independent varible	Regression coefficient	p value
BNP	LA size	0.321	<0.001
	LVEF	−0.282	0.001
	Gender	0.334	0.001
	Urinary albumin	2.875	0.005
	Serum creatinine	2.751	0.007
	BMI	−0.179	0.037
CRP	LVEF	−3.338	0.001
	HDL-C	−2.682	0.009

Note: For BNP, age, gender, body mass index (BMI), urinary albumin, serum creatinine, left atrial (LA) size, left ventricular ejection fraction (LVEF), LV mass index and CRP were included as the independent variables. For CRP, age, BMI, homeostasis model assessment (HOMA)-R, plasma levels for total cholesterol, triglyceride, HDL-C and LVEF were included as independent variables.

Table 5 Univariate and multivariate cox regression analysis

	Univariate			Multivariate
Variables	HR	95% CI		HR	95% CI
Past event	8.535	2.997–24.32	<0.001	4.819	1.299–17.881	0.019
BNP(10 pg/mL)	1.008	1.005–1.011	<0.001	1.007	1.002–1.012	0.01
LVEF (%)	0.92	0.881–0.960	<0.001
ACEI use	0.201	0.077–0.522	<0.001
Creatinine(mg/dL)	7.846	2.723–22.60	<0.001
CRP(0.1 mg/dL)	3.002	1.416–6.364	0.004

Note: Univariate and multivariate models were constructed by Cox regression with forward step wise variable selection. Covariates included in the analysis were as follows: age, gender, body mass index, history of past cardiovascular event, hypertension, hyperlipidemia, fast blood sugar, HbA1c, urinary albumin, BNP, serum creatinine, CRP and LV ejection fraction (LVEF), LV mass index, use of angiotensin converting enzyme inhibitor (ACEI), angiotensin II type 1 receptor blocker, β-blocker, statin, thiazolidinedione and/or aspirin. Hazard ratios (HR) are for an increment in the unit or number shown in parenthesis.

Figure 1 ROC curves and the sensitivity/specificity of BNP (A) or CRP (B) level for predicting the cardiovascular events in diabetic patients. Areas under the ROC curve (AUC) for BNP or CRP are shown in the diagrams.

Figure 2 Incidence of cardiovascular events after 30 months of follow-up by categories of BNP and CRP at baseline. Group I (n = 45), BNP <53 pg/mL and CRP <0.095 mg/dL; group II (n = 10), BNP ≥53 pg/mL and CRP <0.095 mg/dL; group III (n = 32), BNP <53 pg/mL and CRP ≥0.095 mg/dL; group IV (n = 22), BNP ≥53 pg/mL, and CRP ≥0.095 mg/dL.