[Effect of valsartan on postprandial plasma inflammatory factors in patients with essential hypertension].

OBJECTIVE: To explore the effect of valsartan on the concentrations of plasma inflammatory factors after a high-fat meal in patients with essential hypertension in very short time. METHODS: Fifty hypertensive patients and 25 healthy controls were studied. Patients randomly accepted lacidipine 4 mg/d (lacidipine group) or valsartan 80 mg/d (valsartan group) for 1 week. The concentrations of plasma lipid profiles, high-sensitivity C-reactive protein (hsCRP) and soluble P-selectin were measured in fasting state and at 4 h after a single high-fat meal in all subjects at baseline and in patients after 1 week. RESULTS: The concentrations of postprandial plasma hsCRP and soluble P-selectin significantly increased after a high-fat meal in patients (P < 0.05), as compared with those at fasting levels, but not in the controls. The postprandial plasma triglyceride concentrations significantly increased in the healthy controls (P < 0.05), but were lower than those in hypertensive patients (P < 0.01). Postprandial change in plasma concentration of triglyceride was significantly correlated with those of log (hsCRP) (r = 0.344)and soluble P-selectin (r = 0.432), respectively (n = 75, both P < 0.01). Lipids profiles did not change significantly after 1 week. There was no significant difference between the fasting and postprandial plasma concentrations of either hsCRP or soluble P-selectin in valsartan group, while the postprandial increments of inflammatory factors were still significant in the lacidipine group. CONCLUSION: High-fat meal can induce postprandial inflammation response in patients with essential hypertension. Valsartan effectively attenuates this postprandial inflammation response within a very short time.

Postprandial hypertriglyceridemia associated with inflammatory response and procoagulant state after a high-fat meal in hypertensive patients.

OBJECTIVE: To investigate the changes of inflammatory factors and hemostatic variable in plasma after a high-fat meal in normocholesterolemic patients with essential hypertension. METHODS: A total of 60 hypertensive patients were randomly assigned to accept a single high-fat meal (group 1, n=40) or not (group 2, n=20) in the morning after an overnight fast, and 20 healthy participants (group 3) consumed a single high-fat meal on the same day. Plasma lipid profiles, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), soluble P-selectin and plasminogen activator inhibitor type 1 (PAI-1) antigen levels were measured at fasting and 4 h after meal ingestion. RESULTS: Postprandial triglyceride levels increased significantly in groups 1 and 3 (P<0.01), whereas levels were higher in group 1 (P<0.001). Postprandial plasma TNFalpha, hsCRP, soluble P-selectin and PAI-1 antigen levels increased in group 1 (P<0.001) but not in group 3. Postprandial plasma triglyceride level was correlated with log(hsCRP) (P<0.001), TNFalpha (P<0.001), soluble P-selectin (P<0.01) and PAI-1 antigen (P<0.05) levels, respectively. Both postprandial plasma level of soluble P-selectin and that of PAI-1 antigen were positively and significantly correlated with those of log(hsCRP) (P<0.01) and TNFalpha (P<0.001), respectively. CONCLUSION: Postprandial hypertriglyceridemia in hypertensive patients is associated with inflammatory response and procoagulant state.

Effect of fluvastatin and valsartan, alone and in combination, on postprandial vascular inflammation and fibrinolytic activity in patients with essential hypertension.

Postprandial hypertriglyceridemia is associated with a series of atherogenic abnormalities, including a prothrombotic state and inflammation. Hypertensive patients have exaggerated postprandial triglyceride response. The benefit of combined treatment of statin and angiotensin II type 1 receptor blocker (ARB) has been demonstrated in diabetic patients. The aim of this investigation was to explore the effect of a statin, fluvastatin, and the ARB valsartan, alone and in combination, on fibrinolytic activity and inflammation after a high-fat meal in patients with essential hypertension (EHP). A total of 53 EHP patients were studied. The concentrations of plasma lipid profiles, soluble P-selectin, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) antigens were measured in fasting state and at 4 hours after a single high-fat meal (800 calories; 50 g fat). Patients randomly accepted placebo, fluvastatin 40 mg/day, valsartan 80 mg/day, or both for 1 week. Then a high-fat meal and assay of plasma samples were repeated. The postprandial plasma triglyceride, soluble P-selectin, PAI-1, and t-PA antigen concentrations significantly increased after a high-fat meal. Postprandial plasma concentration of triglyceride was significantly correlated with that of soluble P-selectin and PAI-1 antigen, respectively (P<0.001). The postprandial increase in plasma P-selectin, PAI-1, and t-PA antigen levels was attenuated by 1-week fluvastatin-alone and valsartan-alone treatments; their combination is more effective on both fasting and postprandial P-selectin, plasma PAI-1, and t-PA antigen levels. The improvement of these plasma variables was not significantly related to the changes of plasma lipids and blood pressure. In conclusion, postprandial hypertriglyceridemia induces postprandial fibrinolytic dysfunction and vascular inflammation in patients with essential hypertension after a high-fat meal. Short-term combined treatment with fluvastatin and valsartan more effectively inhibits this postprandial atherogenic change in plasma than monotherapy.

[Effect of niacin on adiponectin levels in the adipocytes secretion in rabbits].

OBJECTIVE: To explore the effect of niacin on the serum adiponectin concentration in hypercholesterolemia rabbit and the adiponectin concentration secreted by adipocytes in normal rabbits. METHODS: Ten male New Zealand white rabbits fed with high cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) The high cholesterol group maintained a high cholesterol diet for 8 weeks. (2) The same cholesterol diet plus niacin (0.4g/kg*d ) were administrated for 6 weeks in the niacin group. A control group was fed with normal diet for 14 weeks. Subcutaneous adipose from the control group was collected for adipocyte culture. Matured adipocytes were incubated with various concentrations of niacin (0, 0.25, 0.5, 1.0, and 2.0micromol/L). Adiponectin concentrations in the serum and adipocyte culture supernatant were measured by enzyme-linked-immunosorbent assay. RESULTS: Compared with the control group, rabbits in the high cholesterol group showed higher serum levels of total cholesterol, and low density lipoprotein cholesterol (LDL-C), all of which were significantly reduced by niacin treatment (P<0.01),and serum high density lipoprotein-cholesterol (HDL-C) significantly increased (P<0.01). At 8th week, the mean adiponectin concentration of rabbits fed with high cholesterol diet was significantly lower than that of the control group[(1.268+/-0.039)mg/L vs.(1.449+/-0.107)mg/L,P<0.01]. Niacin treatment significantly elevated the serum adiponectin level which was positively related to HDL-C,and negatively related to TC and LDL-C. Cell experiment in vitro indicated that niacin could significantly induce the adiponectin secretion of adipocytes in a dose-dependent manner. CONCLUSION: Niacin can significantly promote the adiponectin secretion of adipocytes, suggesting that niacin probably has an ability of elevating the serum adiponectin level in addition to lipid-lowering effect.

The effect of atorvastatin on serum myeloperoxidase and CRP levels in patients with acute coronary syndrome.

BACKGROUND: Inflammation is involved in the atherogenesis and pathogenesis of acute coronary syndrome (ACS). As the acute-phase reaction proteins in ACS, myeloperoxidase (MPO) and C-reactive protein (CRP) may play critical roles. Anti-inflammation may be one of benefits of statin drugs in ACS. Studies have showed that statins can suppress serum CRP concentrations. However, whether statins also reduce serum MPO concentrations in patients with ACS is unknown. METHODS: Seventy-eight patients with ACS were randomly separated into Group A and Group B, the patients in Group A receiving conventional therapy, which include no cholesterol-lowering drugs, +atorvastatin (10 mg/day, n=40), the patients in Group B receiving conventional therapy (n=38). The serum concentrations of MPO were measured by enzyme-linked immunosorbent assay (ELISA) and CRP were measured by turbidimetric immunoassay. RESULTS: Serum concentrations of MPO were significantly lower after 1-week therapy in both groups of patients [Group A from 590+/-168 to 496+/-154 microg/l, Group B from 570+/-165 to 521+/-153 microg/l; P<0.01, respectively]. Serum concentrations of CRP also were markedly lower than pretreatment [Group A from 6.56+/-1.87 to 5.14+/-2.07 mg/l; Group B from 6.36+/-1.94 to 5.45+/-1.90 mg/l, P<0.05, respectively]. Compared with conventional therapy alone, atorvastatin significantly further reduced serum MPO [P=0.014] and CRP concentrations [P=0.032]. There were no correlations detected between the reduction of MPO and CRP (r=0.124, P=0.068). CONCLUSIONS: Atorvastatin reduced serum MPO and CRP concentrations in patients with ACS. These effects may explain some clinical benefits of statins in the treatment of these patients.

[Effects of atorvastatin on plasma hypersensitive C-reactive protein and interleukin-6 in patients with acute cerebral infarction].

OBJECTIVE: To observe the effects of different doses of atorvastatin on the plasma hypersensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with acute cerebral infarction. METHODS: 131 patients with acute cerebral infarction, 73 males and 58 females, aged 63 +/- 11, were randomly divided into 3 groups: Group A (n = 47), with basal treatment; Group B (n = 42), atorvastatin 10 mg was added every night; and Group C (n = 42), atorvastatin 20 mg was added every night. Before the treatment and 7 and 14 days after the treatment the plasma levels of hsCRP and IL-6, fasting plasma levels of lipid, such as total cholesterol (TC) and low density lipoprotein-C (LDL-C), liver functions, such as aspartate aminotransferase (ALT) and alanine transaminase (ALT), creatine kinase (CK), urea nitrogen, were detected. Neurological function deficit was determined. The survival condition was surveyed 6 months after. RESULTS: (1) The TC and LDL-C decreased after treatment in the 3 groups with significant differences between Group A and Group C, Group B and Group C, and Group B and Group C (all P < 0.05). (2) The plasma level of hsCRP decreased by 9.1%, 33.9%, and 30.1% respectively 7 days after treatment in Groups A, B, and C with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. The level of hsCRP decreased by 34.3%, 56.0%, and 52.9% respectively 14 days after treatment in the 3 groups with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. (3) The level of IL-6 decreased 7 and 14 days after treatment in all 3 groups, however, without significant differences between any 2 groups (all P > 0.05). (4) The decrease of hsCRP and decrease of IL-6 were not correlated with the percentage of TC decrease (both P > 0.05) in Group B. The decrease of hsCRP was not correlated with the changes of blood lipids in Group C. (5) Both the plasma hsCRP and IL-6 before treatment were positively correlated with the infection volume and neurological function score (all P < 0.01). CONCLUSION: Atorvastatin has an anti-inflammatory action benefiting the alleviation of secondary inflammatory damaged in acute cerebral infarction that is independent of lipid lowering.

[Significance and expression of cyclooxygenase-2 mRNA in peripheral blood monocytes in patients with acute coronary syndrome].

OBJECTIVE: To determine the expression of cyclooxygenase-2 (COX-2) mRNA in peripheral blood monocytes in patients with acute coronary syndrome (ACS), and to explore the effect of the expression of COX-2 mRNA in ACS. METHODS: The expressions of COX-2 mRNA in peripheral blood monocytes from 18 normal subjects and 42 ACS patients were analyzed by reverse transcription polymerase chain reaction (RT-PCR), and the monocytes from patients were incubated with celecoxib in vitro. The concentrations of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in supernates of monocytes were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: The expression of COX-2 mRNA and the secrections of IL-6 and MMP-9 in peripheral blood monocytes in ACS patients significantly increased compared with those from normal controls [0.61 +/- 0.17 vs 0.11 +/- 0.09; (97.24 +/- 11.21) ng/L vs (22.15 +/- 6.30) ng/L; (41.20 +/- 8.41) g/L vs (11.76 +/- 4.23) g/L; all P < 0.05, respectively]. Celecoxib reduced IL-6 and MMP-9 secretion level of monocytes from ACS patients up to 48% and 50% respectively (all P < 0.05), in a concentration-dependent manner. CONCLUSION: COX-2 in peripheral blood monocytes may play an important role in the acute coronary syndrome.

[Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes in patients with acute myocardial infarction and modulates the early inflammatory response].

OBJECTIVE: To measure the effect of atorvastatin on COX-2 expression in monocytes in patients with acute myocardial infarction (AMI). METHODS: Forty patients with AMI (AMI group) and 18 patients with stable coronary heart disease (control group) were enrolled, and patients with AMI were randomly given routine therapy (n = 20) and routine therapy plus atorvastatin (20 mg/day, n = 20) for a week. Peripheral blood monocytes for each participant including patients with AMI were isolated and cultured for 24 hours. During the culture, monocytes in patients with pretreatment AMI were incubated with celecoxib in different concentration (0, 0.1, 1 and 10 micromol/L). COX-2 mRNA expression in monocytes was measured by reverse transcription polymerase chain reaction (RT-PCR); concentrations of interleukin-6 (IL-6) in supernatant from monocytes and plasma hs-CRP levels were measured by using enzyme-linked immunosorbent assay (ELISA). RESULTS: COX-2 expression in monocytes in patients with AMI (0.92 +/- 0.13) was significantly higher than that in the control subjects (0.19 +/- 0.08), and decreased by 66% after atorvastatin (compared with that on routine therapy, P < 0.05); IL-6 secretions of monocytes in the AMI group (204.8 +/- 45.6 ng/L) increased dramatically compared with those in the control group (40.9 +/- 1.2 ng/L, P < 0.05), and reduced dramatically by 58% when incubated with 10 micromol/L celecoxib (P < 0.05) in a concentration-dependent manner; plasma levels of CRP in the AMI group (43.3 +/- 14.9 mg/L) significantly increased compared with those in the control group (1.7 +/- 0.8 mg/L), and reduced by 62% after atorvastatin (compared with those in the routine therapy group, P < 0.05). COX-2 expression in monocytes in the AMI group was positively correlated with both secretions of IL-6 and plasma level of CRP (r = 0.636 and 0.662, respectively, both P < 0.05). CONCLUSIONS: There is an inflammatory activation in peripheral blood monocytes in patients with early AMI, and the monocytes-derived COX-2 may play an important role in promoting early inflammatory process. Atorvastatin may decrease COX-2 expression in peripheral blood monocytes in patients with AMI and cyclooxygenase-dependent pathway might be correlated with the anti-inflammation mechanism of statin.

[Changes and relations of soluble plasma CD40L and matrix metalloproteinase-9 levels in patients with coronary heart disease].

OBJECTIVE: To investigate the serum soluble CD40 ligand (sCD40L) levels in coronary heart disease and its relationship with MMP-9 and to explore the potential predicting factor for the acute coronary syndrome. METHODS: Enzyme-linked immunosorbent assay was used to measure the sCD40L and MMP-9 in 79 patients with coronary heart disease. RESULTS: sCD40L level was significantly higher in patients with acute coronary syndrome [(1.96 +/- 0.84) ng/ml and (2.23 +/- 0.99) ng/ml in unstable angina and acute myocardial infarction group, respectively] than in stable coronary heart disease patients [(1.20 +/- 0.76) ng/ml, P < 0.05]. Serum sCD40L was significantly correlated with MMP-9 (r = 0.401 , P < 0.01), and sCD40L level was significantly correlated with TG (r = 0.254, P = 0.039), HDL (r = -0.234, P = 0.031), and HDL-C (r = -0.253, P = 0.024). CONCLUSION: Serum sCD40L and MMP-9 levels were elevated in acute coronary syndrome, suggesting the possible relation to the pathogenesis of ACS and it may serve as a potential marker of plaque stability.

Atorvastatin reduces plasma MCP-1 in patients with acute coronary syndrome.

BACKGROUND: The monocyte chemoattractant protein-1 (MCP-1) is a chemokine responsible for the recruitment of monocytes to sites of inflammation. MCP-1 may play critical roles in plaque instability. Anti-inflammation may be one benefit of statin drugs in acute coronary syndrome (ACS). We investigated the effects of atorvastatin therapy on plasma MCP-1 concentrations and production of MCP-1 released by peripheral blood monocytes from ACS patients. METHODS: Forty patients with ACS were randomly separated into two groups, those receiving conventional therapy (Group A, n=20), and conventional therapy+atorvastatin (10 mg/day, Group B, n=20). The study the effects of atorvastatin on secretion and expression of MCP-1, human peripheral blood monocytes from healthy donors were incubated with atorvastatin (0.1-10 micromol/l) for up to 24 h in vitro. MCP-1 concentrations in plasma and monocytes culture supernatants were measured by enzyme-linked immunosorbent assays (ELISA). MCP-1 expression was measured by RT-PCR. RESULTS: Plasma concentrations of MCP-1 were significantly lower after 4 weeks therapy in both groups of patients [Group A from 97.4 (50.1-164) to 72.6 (36.3-156) pg/ml, Group B from 101 (60-178) to 45 (29-91) pg/ml, (P<0.05, respectively)]. Compared with conventional therapy alone, atorvastatin significantly further reduced plasma MCP-1 concentrations. There was no significant correlation between the degree of changes in plasma MCP-1 and LDL-C. In vitro, atorvastatin inhibits production of MCP-1 up to 73%, in a concentration-dependent manner, and suppressed MCP-1 expression in peripheral blood monocytes. CONCLUSIONS: Atorvastatin reduced plasma MCP-1 concentrations in patients with ACS. These effects may explain some clinical benefits of statins in the treatment of these patients.

Gemfibrozil reduces release of tumor necrosis factor-alpha in peripheral blood mononuclear cells from healthy subjects and patients with coronary heart disease.

BACKGROUND: Inflammatory process plays an important role in the pathogenesis of coronary heart disease (CHD). With the growing use of gemfibrozil and other fibrates, their anti-inflammatory effects have been noted. But little is known about the effect of gemfibrozil on tumor necrosis factor (TNF)-alpha secretion in peripheral blood mononuclear cells (PBMC) from patients with coronary heart disease. METHODS: PBMC were obtained from CHD patients (n=16) and healthy controls (n=13). PBMC (2x10(6) cells/ml) were cultured in 24-well plates with or without Ang II (10(-8), 10(-7), 10(-6) mol/l), or Ang II (10(-6) mol/l) plus gemfibrozil (10(-6), 10(-5), 10(-4) mol/l). After 24-h incubation, the supernatants were separated, and TNF-alpha was measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Spontaneous release of TNF-alpha was 299.2+/-110.7 pg/ml in PBMC from CHD patients and 179.3+/-78.2 pg/ml in PBMC from control subjects (P<0.05). Incubated with Ang II (10(-8), 10(-7), 10(-6) mol/l), TNF-alpha secretion was 307.7+/-141.8, 318.9+/-135.6, 328.6+/-123.9 pg/ml in PBMC from CHD patients, and 225.3+/-135.4, 224.1+/-141.0,218.7+/-134.8 pg/ml in PBMC from control subjects, respectively. Ang II did not significantly trigger TNF-alpha secretion in both groups. Compared with that incubated with Ang II (10(-6) mol/l) alone, release of TNF-alpha intervened by gemfibrozil (10(-6),10(-5),10(-4) mol/l) decreased to 279.4+/-132.2, 268.0+/-132.7, 226.6+/-102.7 pg/ml in PBMC from CHD patients, and 177.6+/-94.4, 156.1+/-69.4, 105.3+/-52.7 pg/ml in the control group, respectively. Gemfibrozil (10(-5),10(-4) mol/l) significantly inhibited TNF-alpha secretion in both groups (P<0.05). CONCLUSIONS: Our data demonstrated that gemfibrozil reduced release of TNF-alpha in PBMC both from CHD patients and controls. This effect may partially be relevant to the clinical benefits of gemfibrozil in the treatment of dyslipidemia and atherosclerosis.

The lipoprotein lipase Ser447Ter mutation and risk of stroke in the Chinese.

BACKGROUND: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism. The Ser447Ter mutation of LPL may be associated with ischemic cerebrovascular diseases. We investigated whether the LPL variants were related to risk of strokes in Chinese Hans. METHODS: We recruited 160 patients with cerebrovascular diseases (ischemic stroke, n=96; hemorrhagic stroke, n=64) and 117 age-matched controls. All subjects were Chinese Hans. Subjects were analyzed for the Ser447Ter mutation by restriction fragment length polymorphisms of the LPL gene. RESULTS: As compared with controls, the frequency of LPL genotype CG (heterozygous Ser447Ter mutation) was lower in ischemic stroke patients (10.4% vs. 21.4%, p<0.05), and was not significantly different in hemorrhagic stroke patients (15.6% vs. 21.4%, p>0.05). The LPL G allele frequency was also lower in ischemic stroke patients (5.2%) vs. controls (10.7%, p<0.05). There was no difference between hemorrhagic stroke patients (7.8%) and controls. Serum Lp(a) concentrations were markedly lower in CG carriers than that in CC carriers in both stroke patients and the controls (p<0.05). There was no significant difference in the concentrations of other lipids. CONCLUSIONS: Patients with ischemic stroke have a lower frequency of the LPL Ser447Ter mutation, which indicates that this mutation may have protective effect on ischemic stroke.

Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome.

BACKGROUND: Increasing evidence indicates that the CD40-CD40L interaction plays a pivotal role in the inflammatory regulation of atherosclerosis. Adhesion molecules especially the vascular adhesion molecules also play an important role in the pathogenesis of atherosclerosis which act as markers of inflammation. These inflammatory factors render vulnerability to the atherosclerotic plaque by triggering the fissure, rupture, and subsequent thrombosis, leading to the clinical scenario of unstable angina and acute myocardial infarction. METHODS: The difference of sCD40L concentration in different subtype of coronary heart disease and its relationship with vascular adhesion molecules was investigated. Enzyme-linked Immunosorbent Assay (EIA) was used to measure the serum sCD40L, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1). RESULTS: The sCD40L concentration was significantly higher in patients with acute coronary syndrome (ACS) (3.17+/-2.84 ng/ml) than in controls (1.19+/-1.05 ng/ml, p<0.01) and in patients with stable coronary heart disease (1.61+/-1.46 ng/ml, p<0.05). The sCD40L concentration was positively correlated with sICAM-1 (r=0.413, p<0.01), triglycerides (TG) (r=0.23, p<0.05), apoB (r=0.248, p<0.05), and HDL-cholesterol (r=-0.253, p<0.05). CONCLUSIONS: The sCD40L concentration was increased in acute coronary syndrome, suggesting the possible relation of CD40L to the pathogenesis. The serum CD40L concentration was positively correlated with adhesion molecule and was negatively associated with serum high-density lipoprotein cholesterol (HDL-C).