María Elena Soto

Echocardiographic Follow‐Up of Patients with Takayasu's Arteritis: Five‐Year Survival

Takayasus arteritis (TA) is a primary vasculitis that causes stenosis or occlusion, rarely aneurysm and distal ischemia. This study was undertaken to examine cardiovascular damage using echocardiography and determine the causes of morbid‐mortality in Mexican Mestizo patients with TA. Seventy‐six patients were studied by transthoracic echocardiography. Left ventricular diameters, parietal thickness, systolic function, and wall motion were analyzed, also, valvular lesions and aorta features were assessed. Thickness of the interventricular septum was 12 mm ± 3 (8–19), and that of posterior wall was 12 mm ± 2 (9–18). The average left ventricular diastolic diameter was 47 mm ± 7 (33–68) and the left ventricular systolic diameter 32 mm ± 8 (16–64). The left ventricular ejection fraction was of 57 ± 11%. Left ventricular concentric hypertrophy was found in 28 (50%) of the 56 hypertensive patients. The five‐year survival of patients with left ventricular concentric hypertrophy was 80%, compared to 95% in patients without hypertrophy (P = 0.00). Abnormal wall motion was found in 15 patients. Thirty‐one patients had aortic regurgitation, 19 had mitral regurgitation, 13 had tricuspid regurgitation, and 10 and pulmonary hypertension. Six patients had aneurysms of ascending aorta and 7 stenosis of descending aorta. Thirteen of 76 patients died (17%), 85% were hypertensive, and 9% also had acute myocardial infarction (AMI). Echocardiography, a noninvasive technique, shows a great utility in detection and follow‐up of cardiovascular manifestations in patients with TA. New techniques, more sensitive toward detecting the early stages of left ventricular dysfunction, are promising to limit left ventricular hypertrophy development.

Detection of IS6110 and HupB gene sequences of Mycobacterium tuberculosis and bovis in the aortic tissue of patients with Takayasu’s arteritis

BackgroundTakayasu’s arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA.MethodsWe analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; Cases: aortic tissues of individuals with Takayasu’s arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis).ResultsOf 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found.ConclusionWe identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis.

Coronary CT angiography in Takayasu arteritis.

OBJECTIVES The aim of this study was to use coronary computed tomographic (CT) angiography to characterize coronary artery involvement in patients with known Takayasu arteritis who present with anginal chest pain or shortness of breath. BACKGROUND Takayasu arteritis is a primary vasculitis of the large vessels, which mainly affects the aorta and its branches but can also involve the coronary arteries. Coronary CT angiography allows visualization of the coronary vessels and can be used to detect both stenotic and nonstenotic coronary artery lesions. METHODS Eighteen consecutive patients with Takayasu arteritis and angina (typical or atypical) and/or dyspnea underwent contrast-enhanced 64-slice coronary CT angiography. The arterial injury was classified according to the Numano classification. Three patients had prior known coronary artery disease. Coronary arteries were evaluated concerning the presence of obstructive and nonobstructive lesions, and differences between the clinical presentations of patients with and without coronary artery involvement on CT angiography were analyzed. RESULTS Coronary artery involvement was found in 8 patients (44.4%), 3 of them with clinical activity. A total of 19 coronary lesions were present (13 in ostial locations, 5 in proximal coronary artery segments, and 1 in a mid segment). Eight lesions exceeded 50% diameter reduction (2 in ostial locations and 6 in proximal coronary artery segments). Median disease duration was significantly different between patients with coronary artery involvement (176 months; range 13 to 282 months) compared with those without (21 months; range 1 to 142 months) (p = 0.013). CONCLUSIONS Coronary CT angiography allows the assessment of coronary artery involvement in patients with Takayasu arteritis. These data confirm prior observations that most coronary lesions are in ostial or proximal coronary artery locations. Disease duration in patients with coronary artery involvement is longer than in patients without.

Comparative study of the residues 63 and 67 on the HLA-B molecule in patients with Takayasu's arteritis and tuberculosis.

Takayasus arteritis (TA) and tuberculosis (TB) have been associated with major histocompatibility complex genes, especially HLA‐B alleles. However, different HLA‐B alleles have been detected in these diseases. The aim of the study was to compare the distribution of the residues 63 and 67 on the HLA‐B molecule in patients with TA and TB in order to establish a genetic relationship between these two diseases. HLA‐B sequences obtained in 30 patients with TB were compared to those previously reported in TA and healthy controls. 8 out of 30 TB patients studied (26.6%) presented at least one allele with glutamic acid at position 63 and serine at position 67. This was observed in 73% of the TA patients (p = 0.0005). Ten TB (10/30 = 33.3%) and two TA patients (2/26 = 7.7%) did not show similarity at the mentioned positions (p = 0.019). This preliminary study suggests a difference in the distribution of the residues 63 and 67 of the HLA‐B alleles in patients with TA and TB. Copyright

PON1 gene polymorphisms and plasma PON1 activities in Takayasu's arteritis disease.

BACKGROUND Takayasus arteritis (TA) is a chronic inflammation that affects the large vessels; however, its etiology is still unknown. Human serum paraoxonase hydrolyzes oxidized lipids into low-density lipoproteins and could therefore be associated with the prevalence of inflammation processes. Therefore, the purpose of study was to elucidate the influence of PON1 gene polymorphisms and plasma PON1 activities in Takayasus arteritis disease. METHODS Fifty-four patients with TA and 173 clinically healthy Mexicans were studied. The PON1 polymorphism was determined by the TaqMan PCR method. PON1 activity was assessed spectrophotometrically by paraoxon (p-nitrophenylphosphate) hydrolysis. RESULTS In TA patients, the frequency of PON1(192R) allele (51% vs. 39%, P=0.043, OR=1.60, 95% CI=1.03-2.47), PON1(55M) allele (21% vs. 6.6%, P=0.0001, OR=3.80, 95% CI=2.03-7.10), and PON1(-108T) (60.1% vs. 46%, P=0.011, OR 1.79 (95% CI=1.15-2.79) were significantly higher than in healthy controls. PON1 activity was significantly lower for PON in TA vs. controls (136.14 vs. 322.79 μmol min(-1) ml(-1), P=0.001, showing a decreasing activity in all genotypes in TA patients with respect to the control subjects. CONCLUSIONS These results show significantly lower PON1 activity associated with HDL-C in TA patients, this activity could be depending on PON1 genotypes; showing that QR/LM/CT has the lowest hydrolytic activity toward paraoxon meanwhile, PON1(192,55,-108) genetic variations are related with reduced PON1 activities, these could be factors contributing to the development of TA disease.

Participation of Arachidonic Acid Metabolism in the Aortic Aneurysm Formation in Patients with Marfan Syndrome

Marfan syndrome (MFS) is a pleiotropic genetic disease involving the cardiovascular system where a fibrillin-1 mutation is present. This mutation is associated with accelerated activation of transforming growth factor β (TGFβ1) which contributes to the formation of aneurysms in the root of the aorta. There is an imbalance in the synthesis of thromboxane A2 (TXA2) and prostacyclin, that is a consequence of a differential protein expression of the isoforms of cyclooxygenases (COXs), suggesting an alteration of arachidonic acid (AA) metabolism. The aim of this study was to analyze the participation of AA metabolism associated with inflammatory factors in the dilation and dissection of the aortic aneurysm in patients with MFS. A decrease in AA (p = 0.02), an increase in oleic acid (OA), TGFβ1, tumor necrosis factor alpha (TNFα), prostaglandin E2 (PGE2) (p < 0.05), and COXs activity (p = 0.002) was found. The expressions of phospholipase A2 (PLA2), cytochrome P450 (CYP450 4A), 5-lipoxygenase (5-LOX), COX2 and TXA2R (p < 0.05) showed a significant increase in the aortic aneurysm of patients with MFS compared to control subjects. COX1, 6-keto-prostaglandin 1 alpha (6-keto-PG1α) and 8-isoprostane did not show significant changes. Histological examination of the aortas showed an increase of cystic necrosis, elastic fibers and collagen in MFS. The results suggest that there are inflammatory factors coupled to genetic factors that predispose to aortic endothelial dysfunction in the aortic tissue of patients with MFS. There is a decrease in the percentage of AA, associated with an increase of PLA2, COX2/TXA2R, CYP450 4A, and 5-LOX which leads to a greater synthesis of PGE2 than of 6-keto-PGF1α, thus contributing to the formation of the aortic aneurysm. The evident loss of the homeostasis in these mechanisms confirms that there is a participation of the AA pathway in the aneurysm progression in MFS.

Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome.

BACKGROUND Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. PATIENTS AND METHODS Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. RESULTS LPO index, carbonylation, TGF-β1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). CONCLUSIONS The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

Infusion of Hibiscus sabdariffa L. Modulates Oxidative Stress in Patients with Marfan Syndrome

Marfan syndrome (MFS) is associated with progressive aortic dilatation, endothelial dysfunction, and oxidative stress that contribute to the early acute dissection of the vessel and can end up in rupture of the aorta and sudden death. Many studies have described that the organic acids from Hibiscus sabdariffa Linne (HSL) calyces increase cellular antioxidant capacity and decrease oxidative stress. Here we evaluate if the antioxidant properties of HSL infusion improve oxidative stress in MFS patients. Activities of extra cellular super oxide dismutase (ECSOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSSG-R), glutathione (GSH), lipid peroxidation (LPO) index, total antioxidant capacity (TAC), and ascorbic acid were determined in plasma from MFS patients. Values before and after 3 months of the treatment with 2% HSL infusion were compared in control and MFS subjects. After treatment, there was a significant decrease in ECSOD (p = 0.03), EGPx (p = 0.04), GST (p = 0.03), GSH (p = 0.01), and TAC and ascorbic acid (p = 0.02) but GSSG-R activity (p = 0.04) and LPO (p = 0.02) were increased in MFS patients in comparison to patients receiving the HSL treatment and C subjects. Therefore, the infusion of HSL calyces has antioxidant properties that allow an increase in antioxidant capacity of both the enzymatic and nonenzymatic systems, in the plasma of the MSF patients.

Survival and Clinical Behavior of Hypertrophic Cardiomyopathy in a Latin American Cohort in Contrast to Cohorts from the Developed World

Background Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease with diverse phenotipyc, genetic expession and clinical presentations. The evolution of patients with HCM in Latin America has not been properly described being the frequency, the long-term prognosis as well as the predominant phenotypic expression still unknown. The aim of this study was to determine the survival rate of HCM patients having different phenotypes in a Mexican cohort of patients. Methods Clinical and echocardiographic data obtained from 77 Mexican patients with recently diagnosed HCM were analyzed. The follow-up was of 12.5 years. Results 96.1% of patients were in functional class I/II according to the New York Heart Association, 2.6% in class III and 1.3% in class IV. Only 3.9% of them went to surgery for myectomy. During the follow-up, 17 patients (22%) died: 4/9 (44%) had apical HCM, 5/20 (25%) had obstructive septal asymmetric HCM, 6/35 (17%) had nonobstructive septal asymmetric HCM and 2/3 (15%) had concentric HCM. The survival rate was worse for patients with apical HCM, followed by those with obstructive and nonobstructive septal asymmetric HCM and patients showing concentric HCM had the best survival rates. There is significant difference in survival rates which declined in 65% in a 9 years-period. Log rank test showed significant differences (p < 0.002). Conclusion The survival rate of patients with HCM was worse in those with apical variety. The majority of patients received medical treatment. The indication for myectomy was below that observed in other international centers.

Association of the Presence of the IS6110 Gene and the Polymorphisms of the Receptor of the Bactericide P2X7 (A1513C and -762 C/T) in Mexican Patients with Takayasus Arteritis and Tuberculosis. Is the Vasculitis A Manifestation of Extrapulmonary Tuberculosis?

Background and objective: Takayasus arteritis is a disease that has been associated with tuberculosis, based upon the presence of Langerhans giant cells and granulomas. ATP treatment of mycobacteria infected macrophages induces apoptosis mediated via the P2X7 pathway. Here we evaluated if the polymorphisms of the P2X7 receptors are associated to the presence of tuberculosis in Mexican patients with Takayasu´s arteritis. Methods: 63 aortic samples, 33 from Takayasu´s and 30 from tuberculosis subjects were studied. Histological analysis was made and the sequence of the gene IS6110 which identifies the presence of Mycobacterium tuberculosis was amplified. Polymorphisms of the A1513C and -762 C/T receptors for the P2X7 gene were analyzed. Results: The analysis showed a high percentage of extra pulmonary lesions (36.3%) in the Takayasu´s group. No significant differences between the studied genotypes were found in any of the models analyzed or in any of the two P2X7 polymorphisms analyzed. Moreover, an increase in the 1513C allele in presence of IS6110 gene in the Takayasu´s group was observed when comparing with the group of tuberculosis. Conclusion: We found a high percentage of extra pulmonary tuberculosis in subjects with Takayasu´s arteritis; this increase was associated with a high frequency in the allele 1513C in the presence of IS6110 gene. Thus, these alleles may confer a significant susceptibility at the aortic level in the Mexican population having these diseases.