Serum Markers Of Genetic Cardiovascular Disease And Clinical Pathology

Objective:The pathogenesis of idiopathic pulmonary arterial hypertension(IPAH) is unknown,and the syndrome of IPAH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis of IPAH and thus to study their role in the disease process.We prospectively assessed the correlation of TBIL with indexes of right ventricular function as well as with baseline functional status and long-term survival of IPAH patients.Methods:A comparative proteomic analysis was used for clinical screening of serum proteins in 10 patients with IPAH and compared with 10 normal subjects by two dimensional gel electrophoresis(2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).Furthermore,enzyme linked immunosorbent assay(ELISA) was performed for comparison with serum proteins between individual IPAH patients and controls.One hundred and nine consecutive patients with IPAH from February 2001 to June 2008 were retrospectively analyzed and were followed up for 513.6±436.3 day's period.Correlation and survival analysis were performed.Results:Seventy-two women and 37 men with IPAH were consecutively included in the study.They aged 4 to 56 years(mean age,31.6±11.2 years) with 33.9%in NYHA functional classⅠ,15.6%in classⅡ,47.7%in classⅢ,and 2.8%in classⅣ.The survival rate of 1,2 and 3 years was 77.1%,56.9%and 45%respectively.The median baseline serum TBIL concentration was 24.5±14.5μmol/L(range,6.9 to 92μmol/L).TBIL concentration correlated with cardiac index(CI)(r=-0.631,P＜0.01),pulmonary vascular resistance(PVR),pulmonary capillary wedge pressure(PCWP),artery oxygen saturation and right atrial pressure(RAP).TBIL levels were also related to NYHA functional class, cardiothoracic ratio,and diastolic diameter of right ventricle.Receiver operating characteristic analysis identified≥25μmol/L as the best TBIL threshold predicting fatal outcome for IPAH patients(82.8%sensitivity and 71.9%specificity).In multivariate analysis,serum TBIL level(RR:2.26,95%CI:1.28-5.37) was identified as independent factors for poor prognosis among NYHA functional classification,serum creatinine,uric acid and blood urea nitrogen.Nine proteins and their isoforms,including leucine-richα-2-glycoprotein(LRG),haptoglobin precursor,albumin isoform 2,transferrin variant, C3 complement,hydroxypyruvate reductase isoform 1,RAF1,fibrinogen isoformγ-A and fibrinogen isoformγ-B showed significant changes in serum of IPAH patients compared with controls by proteomic analysis.And significant higher serum levels of LRG in IPAH patients compared with controls were found by ELISA.Correlation analysis disclosed a significant association between serum LRG concentrations and New York Heart Association(NYHA) functional class(r=0.71,P＜0.01) and cardiac output (CO)(r=-0.65,P＜0.01).Conclusions:TBIL levels were related to right heart morphology and dysfunction in IPAH patients.Baseline serum TBIL levels of≥25μmol/L identified the group of pulmonary hypertension patients with poor long-term prognosis.These results indicate that there are significant differences in the expression of proteins in the serum of patients with IPAH and normal subjects.And the measurement of LRG,RAF1 and C3 complement levels in the serum may be helpful for the diagnosis of IPAH.In particular, LRG may be a specific prognostical biomarker of IPAH. Objective:To retrospectively analyze the clinical and pathological data of patients with Marfan's syndrome.Methods:The clinical and pathological data were analyzed in 151 patients diagnosed as Marfan's syndrome according to Pyeritz criteria.Results:1.One hundred twelve males and 39 females were enrolled in the study with average age 29.9±11.7 years on admission.Forty-six patients had acute onset shorter than 2 days. And artery dissection was found in 41 cases with the detection rate of 88.6%.Artery dissection was found in 46 cases among 105 patients with acute onset equal or longer than 2 days and the detection rate was 43.8%.The detection rate of artery dissection was significantly different between the two groups.The systolic blood pressure of the patients with or without artery dissection was 127.4±18.2 mmHg and 128.9±20.7mmHg respectively and the diastolic blood pressure 57.1±6.8 mmHg and 53.84±15.9 mmHg respectively.There was no difference between the two groups.Ectopia lentis was found in 33 patients and 28 were bilateral.Vascular system abnormalities were presented in 30 patients.Ninety-seven patients showed skeleton deformity.Other systems malformations were found in 12 patients.2.Ninety-eight patients had abnormal cardiothoracic ratio(0.55±0.09).Ninety-two cases with aortic dilatations were found in 104 patients who underwent computerized tomography(CT) examination.Forty-six artery dissections were found in 80 patients with aneurysm diameter equal or more than 60 mm and 10 artery dissections in 24 cases with diameter less than 60 mm.The detection rate of artery dissection was significantly different between the two groups(P＜0.01).Aortic regurgitation accompanied by mitral regurgitation was found in 5 patients with normal-sized aorta diameter.Of the 5 patients, 4 cases showed left ventricular dilatation.Mucoid degeneration of aortic valve was found in patients with normal diameter of aorta and left ventricle.The value of aneurysm diameter measured by 2-dimensional echocardiography(2-DE) was significantly smaller than those measured during surgery.There was no significant difference between the values by CT and those by the operations.3.The coincidence between the clinical and pathological diagnosis was 90.2%.The patients with atypical pathological manifestations had lower detection rate of artery dissection and aortic regurgitation,and had less diameter of aortic aneurysm and much younger age than those with typical pathological manifestations.Higher detection rate of aortic regurgitation was found in patients with aortic valve degeneration than those without degeneration.The serum high sensitive C reactive proteins(HsCRP) concentrations on admission in patients with acute or old artery dissection or without artery dissection were 23.4±8.5μmol/L,1.41±0.3μmol/L,and 1.28±0.7μmol/L respectively. There was no difference of HsCRP concentrations between the patients with old artery dissection and those without artery dissection.The HsCRP concentrations were significantly higher in patients with acute artery dissection than those with old artery dissection or without artery dissection(P＜0.01).4.Electrocardiogram(ECG) changes included:ST-T depression(59%),mostly seen in precordial leads,left ventricular hypertrophy(41.6%),right ventricular hypertrophy (6%) and arrhythmia(52.3%).Patients with ventricular hypertrophy in ECG had significantly higher left ventricular diastolic diameter and lower ejection fraction than those without ventricular hypertrophy.No significant difference was found in ECG between patients with and without artery dissection.Thirty-one cases had family history. Higher detection rate of deformity was detected in patients with family history.Conclusion:1.Marfan's syndrome is a complicated disease which needs complete methods for correct diagnosis.The acute onset shorter than 2 days may indicate artery dissection.The blood pressure is not a risk factor in Marfan's syndrome.Aortic and mitral regurgitation, and left ventricle dilatation are the subsequent change of aortic valve regurgitation in most cases and this haemodynamic changes occur superior to aortic dilatation in a few cases.2-dimensional echocardiography(2-DE) has less accuracy in measurement of aneurysm diameter than CT.High HsCRP may indicate artery dissection.2.Mucoid degenerations of aortic valve may occur simultaneously with the degeneration of aortic wall.The values of pathological diagnosis should be evaluated.3.ECG can provide some informations of patient's basic disease and cardiac electric change.Patients with family history have higher detection rate of deformity.