Relationship of osteopontin, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, C-reactive protein and target organ damage in patients with essential hypertension

Abstract

Objective To investigate the relationship between osteopontin (OPN), matrix metalloproteinase-2(MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), C-reactive protein (CRP) and target organ damage in patients with essential hypertension. Design and method Clinical and experimental evaluations were conducted in 566 subjects (383 essential hypertension patients and 183 age-, gender-matched normotensive controls) excluding patients with secondary hypertension. The serum levels of OPN, MMP-2, TIMP-1, and CRP were examined. Target organ damage was evaluated, including left ventricular hypertrophy (LVH), carotid intima-media thickness (IMT) and renal impairment. Chronic kidney disease (CKD) was defined as glomerular filtration rate (GFR) below 60 ml/min/1.73 m2. A single first-morning urine albumin/creatinine ratio (ACR) was measured. Results Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-2, TIMP-1, CRP (each P<0.01) and OPN (P<0.05). Spearman's correlation analysis showed that serum levels of OPN (r=0.128, P<0.05) were correlated with IMT. OPN (r=0.283) and CRP (r=0.168) (each P<0.01) were correlated with LVH. TIMP-1 (r=−0.291, P<0.01), OPN (r=−0.480, P<0.01) and CRP (r=−0.238, P<0.01)) were negatively correlated with GFR. OPN (r=0.348, P<0.01) and CRP (r=0.231, P<0.01) were positively correlated with ACR. TIMP-1, OPN, CRP levels were higher in GFR<60 ml/min/1.72 m2 group. Multiple logistic regression analysis showed that OPN (Odds ratio [95%CI], 1.38 [1.03–1.85], P=0.029) was significantly associated with LVH, OPN (Odds ratio [95%CI], 2.40 [1.40–4.13], P=0.002) and CRP (Odds ratio [95%CI], 1.62 [1.15–2.27], P=0.006) were associated with urinary albumin excretion rate after controlling for gender, age, body mass index, systolic BP, diastolic BP, serum total cholesterol, triglyceride and fasting blood glucose. Conclusions These results indicate a strong independent association between inflammatory factors and target organ damage in essential hypertensive patients. Objective To investigate the relationship between osteopontin (OPN), matrix metalloproteinase-2(MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), C-reactive protein (CRP) and target organ damage in patients with essential hypertension. Design and method Clinical and experimental evaluations were conducted in 566 subjects (383 essential hypertension patients and 183 age-, gender-matched normotensive controls) excluding patients with secondary hypertension. The serum levels of OPN, MMP-2, TIMP-1, and CRP were examined. Target organ damage was evaluated, including left ventricular hypertrophy (LVH), carotid intima-media thickness (IMT) and renal impairment. Chronic kidney disease (CKD) was defined as glomerular filtration rate (GFR) below 60 ml/min/1.73 m2. A single first-morning urine albumin/creatinine ratio (ACR) was measured. Results Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-2, TIMP-1, CRP (each P<0.01) and OPN (P<0.05). Spearman's correlation analysis showed that serum levels of OPN (r=0.128, P<0.05) were correlated with IMT. OPN (r=0.283) and CRP (r=0.168) (each P<0.01) were correlated with LVH. TIMP-1 (r=−0.291, P<0.01), OPN (r=−0.480, P<0.01) and CRP (r=−0.238, P<0.01)) were negatively correlated with GFR. OPN (r=0.348, P<0.01) and CRP (r=0.231, P<0.01) were positively correlated with ACR. TIMP-1, OPN, CRP levels were higher in GFR<60 ml/min/1.72 m2 group. Multiple logistic regression analysis showed that OPN (Odds ratio [95%CI], 1.38 [1.03–1.85], P=0.029) was significantly associated with LVH, OPN (Odds ratio [95%CI], 2.40 [1.40–4.13], P=0.002) and CRP (Odds ratio [95%CI], 1.62 [1.15–2.27], P=0.006) were associated with urinary albumin excretion rate after controlling for gender, age, body mass index, systolic BP, diastolic BP, serum total cholesterol, triglyceride and fasting blood glucose. Conclusions These results indicate a strong independent association between inflammatory factors and target organ damage in essential hypertensive patients.