[Relationship between paraoxonase 1 55 Met/Leu, paraoxonase 2 148 Ala/Gly genetic polymorphisms and coronary artery disease].

OBJECTIVE: To study the relationships between paraoxonase 1 55 Met/Leu (PON1 55Met/Leu), paraoxonase 2 148 Ala/Gly(PON2 148Ala/Gly) genetic polymorphisms and coronary artery disease(CAD), plasma activities of paraoxonase (PON), total superoxide dismutase (T-SOD), as well as plasma concentration of maleic dialdehyde (MDA). METHODS: The PCR-RFLP method was applied to identify the genetic polymorphisms of PON1 55Met/Leu and PON2 148Ala/Gly, and the colorimetry way was used to detect plasma activities of PON, T-SOD and plasma MDA concentration of 262 CAD patients and 100 controls. RESULTS: Comparing with control, the CAD patient had the obviously lower activities of enzymes PON (349.27+/- 138.36 nmol/min.mL vs 454.75+/- 166.00 nmol/min.mL, P< 0.001) and T-SOD (23.61+/- 16.51 U/mL vs 44.01+/- 22.68 U/mL, P< 0.001) while getting the plasma MDA concentration increased markedly(2.47+/- 0.73 nmol/mL vs2.15+/- 0.55 nmol/mL, P< 0.01). The CAD patient had more LM genotype and M allele of PON1 55Met/Leu(24.8% vs 1.4%, P< 0.001 and 12.4% vs 0.5%, P was 0.001 respectively), GG and AG genotype and G allele of PON2 148 Ala/Gly(11.8% vs 5.0%, P< 0.001; 48.1% vs 24.0%, P< 0.001 and 36.0% vs 17.0%, P< 0.001 respectively) than control did. The activities of plasma PON and T-SOD were lower in individuals with PON??1 55 LM genotype than those with LL genotype(304.73+/- 125.04 vs 394.84+/- 154.87 nmol/min.mL and 24.89+/- 16.14 vs 30.22+/- 21.29 U/mL, P< 0.001 and P< 0.05 respectively). The activity of plasma PON was also lower in individuals with PON2 148 GG/AG genotype than that with AA genotype(281.47+/- 84.70 vs 356.00+/- 145.95 vs 417.34+/- 159.00 nmol/min.mL, P< 0.001). Logistic regression analysis showed that PON1 55 LM genotype (OR 29.08, 95%CI 2.88-294.04, P was 0.004) and M allele(OR 15.17, 95%CI 1.32-174.29, P was 0.029), PON2 148 GG/AG genotype (OR 2.32, 95%CI 1.52-3.54, P< 0. 001) and G allele (OR 3.24, 95%CI 1.38-7.61, P was 0.007) were independent risk factors for CAD. CONCLUSION: The CAD patient has the obviously low activities of plasma PON and T-SOD but on the contrary, get the plasma MDA concentration increased markedly. PON1 55 LM genotype and M allele, PON2 148 GG/AG genotype and G allele are the risk factors for coronary artery disease, and the activity of plasma PON is also markedly reduced in individuals with above genotypes.

[Study of the association between paraoxonase1 55 Met/Leu, paraoxonase2 148 Ala/Gly and manganese superoxide dismutase (MnSOD) 9 Ala/Val genetic polymorphisms and coronary heart disease].

OBJECTIVE: To study the associations between paraoxonase, 55 Met/Leu (PON1 55 Met/ Leu), paraoxonase2 148 Ala/Gly (PON2 148 Ala/Gly) and manganese superoxide dismutase 9 Ala/Val (MnSOD 9 Ala/Val) genetic polymorphisms and coronary heart disease (CHD), plasma activities of paraoxonase (PON), total superoxide dismutase (T-SOD), MnSOD, as well as plasma concentration of maleic dialdehyde (MDA). METHODS: Using PCR-RFLP method to identify genotype of PON1 55 Met/Leu, PON2 148 Ala/Gly and MnSOD 9 Ala/Val genetic polymorphisms, and using colorimetry to detect plasma activities of PON, T-SOD, MnSOD and plasma concentration of MDA in 262 CHD patients and 100 controls. RESULTS: Compared with controls, the plasma activities of PON [(349.27 +/- 138.36 vs. 454.75 +/- 166.00) nmol x min(-1) x ml(-1), P < 0.001], T-SOD [(23.61 +/- 16.51 vs. 44.01 +/- 22.68) U/ml, P < 0.001] and MnSOD [(21.56 +/- 13.11 vs. 28.79 +/- 8.65) U/ml, P < 0.001] reduced obviously,while plasma MDA concentration increased markedly [(2.47 +/- 0.73 vs. 2.15 +/- 0.55)nmol/ml, P < 0.01] in CHD patients. There were more LM genotype and Met allele of PON, 55 Met/Leu (24.8% vs. 1.4%, P < 0.001 and 12.4% vs. 0.5%, P = 0.001, respectively), GG and AG genotype and G allele of PON2 148 Ala/Gly (11.8% vs. 5.0%, P < 0.001, 48.1% vs. 24.0%, P < 0.001 and 36.0% vs. 17.0%, P < 0.001, respectively) and AA genotype, A allele of MnSOD 9 Ala/Val genetic polymorphisms (64.2% vs. 43.0%, P = 0.001 and 80.0% vs. 67.0%, P = 0.014, respectively) in CHD patients than in controls. The activities of plasma PON and T-SOD were lower in individuals with PON1 55 LM genotype than those with LL genotype. The activity of plasma PON was also lower in individuals with PON2 148 GG/AG genotype than those with AA genotype. The activities of plasma PON and MnSOD depressed in individuals with MnSOD AA genotype compared with those with VV genotype. Logistic regression analysis demonstrated that PON1 55 LM genotype, PON2 148 GG/AG genotype and G allele were independent risk factors for CHD. CONCLUSION: The antioxidative ability decreased, while lipid superoxide increased in CHD patients. Gene polymorphisms of PON1 55 Met/Leu, PON2 148 Ala/Gly and MnSOD 9 Ala/Val seemed to involve in the morbidity of CHD by influencing the plasma activities of PON and MnSOD.

Value of echocardiography for observing left ventricular hypertrophy in the diagnosis of myocardial microvascular damage in hypertensives.

OBJECTIVE: To investigate the value of the echocardiographic observation of the left ventricular hypertrophy (LVH) in diagnosing myocardial microvascular damage in patients with essential hypertension (EH). METHODS: After intravenous injection with Quanfuxian (a contrast agent consisting of albumin and C3F8 prepared by Nanfang Hospital), the values of A (the maximum number of microbubbles accumulating in the local tissues for assessing the density of local microvessels), beta (the filling velocity of contrast agent for evaluating local blood flow velocity) and A x beta (the product of A and beta for estimating local myocardial blood flow) at rest and after dipyridamole injection were measured by intermittent harmonic imaging with myocardial contrast echocardiography (MCE). The ratios of A and beta along with the microvascular coronary flow velocity reserve (CFVR) were also calculated. RESULTS: Compared with the control group, the rest values of A, beta and A.beta in EH patients were higher, especially in those with LVH. After dipyridamole injection, the values of A, beta, A x beta and the ratios of A and beta, along with CFVR as well, were significantly lowered (P <0.01), and the reductions were especially obvious in LVH cases. As the hypertension exacerbated, the values of A and A x beta tended to increase in positive correlation with systolic and diastolic blood pressure (P <0.01), while the ratio of A and CFVR were decreased, the latter was inversely correlated with diastolic blood pressure (r=-0.55, P <0.01). Positive correlations were noted of the values of A and A x beta with the left ventricular mass and left ventricular mass index (P <0.01). CONCLUSION: EH patients, especially those with LVH, are characterized by increased rest myocardial microvascular blood flow, impaired myocardial microvascular flow reserve and endothelium independent vasodilation relaxing ability, and reduced capillary density, and these conditions tend exacerbate as the disease worsens. Microvascular function impairment should be suspected when complication of LVH arises in the EH patients. As a new important noninvasive technique, MCE can be a promising modality for diagnosing microvascular disease in essential hypertension.

[Effects of fluvastatin on the levels of C-reactive protein and lipids in patients with hyperlipidemia].

OBJECTIVE: To observe the changes of C-reactive protein (CRP) level and its relationship with blood lipids, and the effects of fluvastatin on CRP and the lipids in patients with hyperlipidemia. METHODS: Serum levels of cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C) and lipoprotein(a)[Lp(a)] were measured by enzyme assay, and plasma CRP level by immunonephelometry before and after fluvastatin treatment (20 mg/d for 4 weeks) in patients with hyperlipidemia. RESULTS: CRP levels were above normal in 90.3% hyperlipidemia cases in spite of the various accompanying diseases. Fluvastatin treatment significantly reduced TC (-7.49%), TG (-14.32%), LDL (-13.88%), VLDL (-18.48%) and TC/HDL(-13.50%) levels (P<0.01), and also brought down Lp(a) concentration (-13.81%). CRP levels was very effectively reduced after the treatment (-15.92%, P<0.001). No association between basal CRP levels and basal lipids and Lp(a) concentrations was observed. Positive correlation of CRP, however, was observed after fluvastatin treatment with TC/HDL (r=0.62, P=0.041) and Lp(a) (r=0.320, P=0.011), while inverse relations were noted between CRP and HDL (r=-0.288, P=0.023). CONCLUSION: CRP levels increases markedly in patients with hyperlipidemia, a fact that is independent of the accompanying diseases. In addition to modulating blood lipid levels, fluvastatin also reduces CRP level, the latter possibly serving as an independent predictive factor for atherosclerotic cardiovascular diseases and also as an indicator for estimating the effectiveness of the treatment.

[Coagulative and fibrinolytic changes in patients with essential hypertension and the effect of sustained-release nifedipine].

OBJECTIVE: To investigate the changes of coagulation and fibrinolysis status in patients with essential hypertension (EH) and observe the therapeutic effect of sustained-release nifedipine. METHODS: Ninety-nine EH patients were divided according to their diastolic blood pressure (DBP) into mild group (48 cases), moderate group (29 cases) and severe group (22 cases), and 25 patients among the groups were chosen at random to receive sustained-release nifedipine for 2 weeks. Twenty healthy subjects served as control group. Plasma D-dimer (DD), fibrin monomer (FM) and tissue-type plasminogen activator (tPA) levels were determined in all the subjects by enzyme-linked immunosorbent assay (ELISA). RESULTS: The plasma DD and FM levels were much higher, while tPA level was much lower in hypertensives than those of normal controls, exacerbating with the severity of the disease. DBP was positively correlated with plasma FM level (r=0.374,P<0.001). In patients with left ventricular hypertrophy, left ventricular enlargement and left atrial enlargement, higher levels of DD, FM and tPA were detected. Nifedipine treatment produced significant reduction in plasma DD and FM levels along with the increase in tPA level [DD: (40.7+/-23.5) mg/dl vs (23.8+/-16.5) mg/dl; FM: (7.0+/-1.6) ng/microliter vs (4.8+/-1.5) ng/microliter tPA: (0.31+/-0.14) ng/ml vs(0.41+/-0.05) ng/ml, P<0.001]. CONCLUSION: Enhanced coagulative activity and lowered fibrinolytic activity characterize EH patients and nifedipine may correct this disorder.