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Study On The Correlation Between Pentameric 3 And Pulse Wave Velocity And Cardiovascular Disease

Posted on:2014-01-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z G WangFull Text:PDF
GTID:1314330518491363Subject:Internal Medicine
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Section 1. The association of PTX3 genetic variations with Takayasu arteritisBackgroundsTakayasu arteritis is a chronic, systemic,inflammatory disease that primarily affects the aorta and its main branches. The pathogenesis of TA is still unclear, but it is widely believed to be a genetic-related autoimmune and inflammatory disease.Pentraxin-3 (PTX3) is a multifunctional cytokine that plays an important role in inflammation and immunity. However, however, the association of PTX3 gene variants with expression levels and TA has not been documented in Chinese population so far.MethodsA total of 100 TA patients and 200 age and sex matched healthy controls were included into the study. All patients fulfilled the American College of Rheumatology 1990 criteria for the diagnosis of TA. DNA was extracted from peripheral venous blood. Genotyping of PTX3 was performed using a PCR-LDR (polymerase chain reaction -ligase detection reaction) method. Serum level of PTX3 was tested by ELISA assay.ResultsThere were no significant differences in the distribution of PTX3 gene(rs2305619 G/A, rs3816527 A/C, rs3911403 T/A and rs4680367 T/C) genotype frequencies between TA patients and healthy controls (all P>0.05). The four haplotypes of PTX3 gene showed no significant risk to TA (all P>0.05). Plasma level of PTX3 were obtained for 60 TA patients and 30 healthy controls, and the level of PTX3 was significantly higher in the active TA patients than that in the inactive TA patients and healthy controls (all P<0.05). Plasma level of PTX3 in the healthy controls carrying rs2305619A was significantly higher than that in the healthy controls not carrying the allele (all P<0.05). Plasma level of PTX3 in the inactive TA patients carrying rs2305619A was significantly higher than that in the inactive TA patients not carrying the allele (all P<0.05). The used dose of prednisone was significantly higher in the active TA patients carrying rs2305619A than that in the active TA patients not carrying the allele (P<0.05).ConclusionsThis study is the first to investigate the association of the variants of PTX3 gene with its expression level and the development of TA in Chinese Han population. We did not find the significant association of the variants of PTX3 gene (rs2305619 G/A,rs3816527 A/C, rs3911403 T/A and rs4680367 T/C) with the development of TA in this study. The allele of rs2305619 G/A may be significantly associated with the expression level of PTX3 in Chinese Han population, therefore, the development and therapy for TA patients in Chinese Han population may be significantly influenced by this allele. The expression level of PTX3 is related with TA disease activity,suggesting PTX3 play an important role in the development of TA in Chinese Han population.Section 2. The association of brachial-ankle pulse wave velocity with Takayasu arteritisBackgroundsAs an independent determinant of cardiovascular risk, arterial stiffness is regulated by both structural and functional factors. Takayasu arteritis (TA) is a rare inflammatory large-vessel vasculitis. However, relationship of TA and arterial stiffness measured as brachial-ankle pulse wave velocity (ba-PWV) has not been well determined.MethodsSixty-seven patients with TA (43 active, 24 inactive) and 67 age and sex-matched healthy controls were studied. Arterial stiffness assessed by ba-PWV was obtained.Resultsba-PWV was significantly higher in TA patients than that in healthy controls(1495.55 ± 431.72 vs. 1211.37 ± 154.42cm/s,P<0.001). Although active TA patients were younger than inactive TA patients, ba-PWV was significantly higher in active TA patients compared with that in inactive TA patients (1,553.72 ± 451.76 vs. 1,381.75 ±373.33 cm/s,P=0.04). Multiple liner regression analysis indicated that TA was independently related to ba-PWV (β =403.60, R2=0.419, P <0.001). ba-PWV did not correlate with c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in overall TA patients (both P >0.05). In TA patients without immunosuppression therapy, ba-PWV significantly correlated with CRP (r=0.419, P=0.008), but not ESR(P>0.05). Multiple logistic regression analyses indicated that ba-PWV was an independent predictor of active TA in overall TA patients (OR= 1.003, 95%CI=1.001-1.006; P=0.046) and in TA patients without immunosuppression therapy(OR=1.005, 95% CI=1.001-1.011; P=0.042).ConclusionsThis study indicates that arterial stiffness measured as ba-PWV is significantly elevated in TA patients, especially in active TA patients, and ba-PWV may be associated with inflammation and disease activity in TA patients.Section 3. The association of brachial-ankle pulse wave velocity with Takayasu arteritis and coronary artery diseaseBackgroundsAs an independent determinant of cardiovascular risk, arterial stiffness is regulated by both structural and functional factors, including inflammation. Both takayasu arteritis (TA) and coronary artery disease (CAD) are vascular diseases with inflammation playing an important role in vascular damage. However, no study has been conducted to investigate and compared arterial stiffness in TA and CAD.MethodsWe excluded all patients with hypertension in this study to control the influence of hypertension on our results. Fifty TA patients and 40 CAD patients were enrolled in this study. Arterial stiffness was assessed by ba-PWV in TA patients and CAD patients.ResultsNo difference of blood pressure was found between TA patients and CAD patients (SBP,119.41 ± 13.10 vs. 112.69±11.46 mmHg,P>0.05; DBP,72.52±14.28 vs.67.17±7.95mmHg,P>0.05; MAP,89.34± 15.11 vs. 82.55±9.46mmHg,P>0.05; PP,38.95±12.35 vs. 41.52±6.94 mmHg, P>0.05). ESR, CRP, white blood cell count(WBC), lymphocyte count and ba-PWV were significantly higher in active TA patients than that in inactive TA patients (ESR,16.36±18.93 vs. 7.74±4.48 mm/h,P<0.001; CRP, 8.10±15.02 vs. 2.89±1.83 mg/L, P<0.001; WBC, 10.24±3.68 vs.8.13±2.29 109/L,P<0.001; lymphocyte count,2.41 ± 1.36 vs. 1.51±0.57 1 09/L,P<0.001; ba-PWV, 1,553.72±451.76 vs. 1,381.75±373.33 cm/s, P<0.001) .WBC,ESR and CRP were significantly higher in overall TA patients than that in CAD patients(WBC, 9.528±3.273 vs. 6.281±1.757 1 09/L,P<0.001 ESR (8.75±10.72 vs.12.68±10.40mm/h,P<0.001; CRP,4.28±4.88 vs. 7.18±14.47 mg/L,P<0.001)。Although overall TA patients were significantly younger than CAD patients (Age,42.53±12.53 vs. 51.00±9.46 岁,P<0.001),but ba-PWV was significantly higher in overall TA patients than that in CAD patients (1588.39±407.42 vs.1321.07±180.87cm/s,P<0.001) . ba-PWV was significantly higher in active TA patients than that in CAD patients (ba-PWV,1,551.72±411.76 vs. 1321.07±180.87 cm/s, P<0.001) . ba-PWV was higher in inactive TA patients than that in CAD patients,but not to a significant level (ba-PWV,1,381.75±373.33 vs. 1321.07±180.87 cm/s,P>0.05).In the multiple liner regression analysis,TA (β=-458.753,P<0.001)、SBP (β=9.918, P<0.001) 、BMI (β=29.526, P<0.001) and heart rate (β=9.296,P=0.005) were significantly associated with ba-PWV in overall enrolled patients(R2=0.610) . There were no significant association between ba-PWV and ESR and CRP in CAD patients and overall TA patients (all P>0.05). In TA patients without immunosuppression therapy, ba-PWV was significantly correlated with CRP(r=0.372,P=0.03),but not ESR (r=0.235, P>0.05).ConclusionsArterial stiffness was significantly higher in TA patients than that in CAD patients,suggesting a more severe vascular damage in TA patients compared with that in CAD patients,highlighting the importance of detecting arterials stiffness in TA patients.Inflammation was more severe in TA patients than that in CAD patients, and it may at least partly explain why the arterial stiffness was higher in TA patients than that in CAD patients.Section 4. Relationships between use of statins and arterial stiffness in normotensive and hypertensive patients with coronary artery diseaseBackgroundStatins were suggested to improve arterial stiffness in patients with coronary artery disease (CAD). Hypertension is a predominant contributor of arterial stiffness.However, the influence of hypertension on the effect of statins on arterial stiffness in CAD patients is unknown. Therefore,in this study,we evaluated the relationships between the use of statins and arterial stiffness in normotensive and hypertensive CAD patients.MethodsBrachial-ankle pulse wave velocity (ba-PWV) was measured in 437 patients,including 220 hypertensive CAD patients (121 used statins, 99 did not) and 217 normotensive CAD patients (105 used statins, 112 did not). The normotensive and hypertensive CAD patients were age, sex, and BMI matched.ResultsIn normotensive and hypertensive CAD patients, lipid profiles were significantly improved in statins group compared with that in non-statins group. ba-PWV in statins group was significantly lower compared with that in non-statins group in normotensive CAD patients (1,331.68±167.52 vs. 1,468.61±244.54 cm/s,P=0.002),but not in hypertensive CAD patients (P>0.05). In multiple linear regression analyses,statins therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients (P=0.018), but not in hypertensive CAD patients (P>0.05).ConclusionsStatins may significantly improve arterial stiffness in CAD patients, and hypertension may probably influence the effectiveness of statins therapy on arterial stiffness in this population. Further studies are needed to investigate the effect of statins on arterial stiffness in normotensive and hypertensive CAD patients.
Keywords/Search Tags:Takayasu arteritis, PTX3, Single neucleotide polymorphism, Haplotype, Arterial stiffness, pulse wave velocity, disease activity, arterial stiffness, statins, hypertension, coronary artery disease
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