Angiopoietin‐2 levels as a biomarker of cardiovascular risk in patients with hypertension

Figures & data

Table I. Base‐line characteristics and plasma indices of angiogenesis in 251 patients with hypertension enrolled in ASCOT. Values are n (%), mean (SD), or *median (IQR = interquartile range).

Age (years)	63.5 (7.4)
Male gender (%)	251 (84.6)
Smoking history (%)	52 (20.7)
Caucasian ethnicity (%)	214 (85.3)
Statin therapy (%)	153 (61.2)
Antiplatelet therapy (%)	97 (40.2)
Diabetes (%)	63 (25.0)
Impaired fasting glucose (%)	41 (17.4)
Ischaemic heart disease (%)	20 (8.0)
Cerebrovascular disease (%)	19 (7.6)
Target organ damage (%)	57 (22.7)
ACE inhibitor therapy (%)	119 (47.6)
Βeta‐blocker therapy (%)	118 (47.2)
More than two antihypertensive therapy use (%)	112 (44.6)
Angiopoietin‐1 (ng/mL)*	10 (5–21)
Angiopoietin‐2 (pg/mL)*	1300 (1900–3400)
Angiopoietin receptor‐tyrosine kinase Tie‐2 (ng/mL)*	12 (10–26)

ACE, angiotensin converting enzyme.

Table II. Base‐line and 6‐year follow‐up of hypertensive patients: indices of risk management. Data are given as mean (SD).

Risk factors	Base‐line		6‐year follow‐up		P‐value
Body mass index (kg/m^2)	29.2	(4.6)	29.1	(4.9)	0.56
Systolic blood pressure (mmHg)	167	(17)	141	(17)	<0.001
Diastolic blood pressure (mmHg)	91.0	(10.4)	77.3	(10.1)	<0.001
Pulse pressure (mmHg)	75.2	(15.3)	62.2	(13.6)	<0.001
Fasting plasma glucose (mmol/L)	6.66	(2.56)	6.56	(2.13)	0.50
Serum cholesterol (mmol/L)	6.01	(1.21)	4.58	(1.03)	<0.001
Serum triglycerides (mmol/L)^a	1.7	(1.2–2.3)	1.2	(0.9–1.8)	<0.001
HDL cholesterol (mmol/L)	1.33	(0.37)	1.40	(0.41)	<0.001
Creatinine (µmol/L)^a	101	(93–111)	106	(96.5–120)	<0.001
Glomerular filtration rate mL/min/1.73 m^2	74.1	(61.0–90.2)	62.6	(53.1–78.8)	<0.001

^aData are given as median (interquartile range). HDL, high density lipoprotein.

Figure 1 Kaplan‐Meier cumulative event‐free survival charts between tertiles of plasma angiopoietin‐2 levels, in relation to cardiovascular outcomes. A: Composite cardiovascular outcomes; B: myocardial infarction; C: ischaemic cerebrovascular events.

Table III. Area under the curve (AUC) analysis of angiopoietin‐2 and cardiovascular risk factors with incident vascular outcomes in 192 hypertension patients free of cardiovascular events at base‐line.

Base‐line variables	Incident myocardial infarction				Incident stroke/TIA				Incident composite vascular outcomes
	Area	95% CI		P	Area	95% CI		P	Area	95% CI		P
Body mass index (kg/m^2)	0.648	0.464	0.832	0.18	0.713	0.568	0.857	0.011	0.582	0.463	0.701	0.16
Systolic blood pressure (mmHg)	0.458	0.225	0.691	0.71	0.417	0.268	0.566	0.31	0.509	0.390	0.628	0.87
Diastolic blood pressure (mmHg)	0.413	0.196	0.630	0.43	0.428	0.289	0.567	0.38	0.446	0.337	0.555	0.35
Plasma glucose (mmol/L)	0.577	0.321	0.834	0.49	0.421	0.273	0.568	0.34	0.541	0.421	0.661	0.47
Total to HDL cholesterol ratio	0.504	0.240	0.767	0.97	0.533	0.339	0.727	0.69	0.485	0.353	0.618	0.80
Angiopoietin‐1 (ng/mL)	0.697	0.531	0.863	0.08	0.450	0.307	0.593	0.55	0.490	0.384	0.597	0.87
Angiopoietin‐2 (pg/mL)	0.745	0.630	0.859	0.028	0.550	0.399	0.701	0.55	0.568	0.458	0.679	0.24
Angiopoietin receptor‐tyrosine kinase Tie‐2 (ng/mL)	0.551	0.363	0.738	0.65	0.516	0.325	0.708	0.84	0.510	0.394	0.626	0.87

HDL, high density lipoprotein, TIA, transient ischaemic attack.

Table IV. Cox regression analysis of cardiovascular risk factors and raised plasma angiopoietin‐2 (>4.3 pg/mL) at base‐line with incident MI in hypertension patients.

Risk factors at base‐line	Exp(beta)	95% CI Exp(beta)		P
Raised angiopoietin‐2	8.10	1.01	65.15	0.049
Age (years)	1.09	0.97	1.23	0.15
Male gender	1.41	0.26	7.79	0.69
Smoking history	0.68	0.12	3.96	0.67
Diabetes mellitus	5.39	1.36	21.45	0.017
ACE inhibitor therapy	1.94	0.35	10.83	0.45
Statin therapy	0.40	0.08	2.08	0.28
Βeta‐blocker therapy	0.79	0.15	4.11	0.78
Body mass index (kg/m^2)	1.04	0.89	1.22	0.62
Systolic BP (mmHg)	0.99	0.95	1.03	0.57
Serum triglycerides (mmol/L)	0.96	0.46	2.02	0.92
Total to HDL cholesterol ratio	1.46	1.01	2.11	0.046
History of cardiovascular events	0.70	0.17	2.97	0.63

Exp(beta) is the predicted change in the onset of myocardial infarction for a unit increase in the predictor. ACE, angiotensin converting enzyme, BP, blood pressure, HDL, high density lipoprotein.