Ischemic heart disease and correlates in adults from Ribeirao Preto, Brazil

OBJECTIVE: To identify the prevalence of ischemic heart disease (IHD) and correlates in an adult population. METHODS: Cross-sectional population-based epidemiological study including a weighted sample of 2,471 adults of both sexes and with age 30 years or older residing in Ribeirao Preto, Southeastern Brazil, in 2007. The Rose Questionnaire was administered, and IHD prevalence was calculated with point estimates and 95% confidence intervals. To identify correlates (sociodemographic, cardiovascular risk factors, and those related to access to health services and to physical activity level), crude and adjusted prevalence ratios were estimated using Poisson regression. RESULTS: IHD prevalence was higher in females than males at all age strata. In the final model, the following variables were independently associated with IHD: work status (PR = 0.54 [0.37; 0.78]); family history of IHD (PR = 1.55 [1.12;2.13]); hypertension (PR = 1.70 [1.18;2.46]); self-reported health status (PR=2.15 [1.40;3.31]); smoking duration (third tertile) (PR=1.73 [1.08;2.76]); adjusted waist circumference (PR=1.79 [1.21;2.65]) and hypertriglyceridemia (PR=1.48 [1.05;2.10]). Linear trend test of PR across self-reported health status categories was statistically significant (p<0.05). CONCLUSIONS: A high prevalence of IHD was found, and the factors associated with the outcome are almost all modifiable and potentially influenced by public policy interventions.

Transcriptome Analysis of Renal Ischemia/Reperfusion Injury and Its Modulation by Ischemic Pre-Conditioning or Hemin Treatment

Ischemia/reperfusion injury (IRI) is a leading cause of acute renal failure. The definition of the molecular mechanisms involved in renal IRI and counter protection promoted by ischemic pre-conditioning (IPC) or Hemin treatment is an important milestone that needs to be accomplished in this research area. We examined, through an oligonucleotide microarray protocol, the renal differential transcriptome profiles of mice submitted to IRI, IPC and Hemin treatment. After identifying the profiles of differentially expressed genes observed for each comparison, we carried out functional enrichment analysis to reveal transcripts putatively involved in potential relevant biological processes and signaling pathways. The most relevant processes found in these comparisons were stress, apoptosis, cell differentiation, angiogenesis, focal adhesion, ECM-receptor interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory response, olfactory transduction and regulation of actin cytoskeleton. In addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT, Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and coagulation cascade. Also, new insights were gained about the underlying protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn diagram analysis allowed us to uncover common and exclusively differentially expressed genes between these two protective maneuvers, underscoring potential common and exclusive biological functions regulated in each case. In summary, IPC exclusively regulated the expression of genes belonging to stress, protein modification and apoptosis, highlighting the role of IPC in controlling exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn, exclusively regulated the expression of genes associated with cell differentiation, metabolic pathways, cell cycle, mitosis, development, regulation of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic effect for Hemin. These findings improve the biological understanding of how the kidney behaves after IRI. They also illustrate some possible underlying molecular mechanisms involved in kidney protection observed with IPC or Hemin treatment maneuvers.

Early dystrophin disruption in the pathogenesis of experimental chronic Chagas cardiomyopathy

Chronic Chagas cardiomyopathy evolves over a long period of time after initial infection by Trypanosoma cruzi. Similarly, a cardiomyopathy appears later in life in muscular dystrophies. This study tested the hypothesis that dystrophin levels are decreased in the early stage of T cruzi-infected mice that precedes the later development of a cardiomyopathy. CD1 mice were infected with T cruzi (Brazil strain), killed at 30 and 100 days post infection (dpi), and the intensity of inflammation, percentage of interstitial fibrosis, and dystrophin levels evaluated. Echocardiography and magnetic resonance imaging data were evaluated from 15 to 100 dpi. At 30 dpi an intense acute myocarditis with ruptured or intact intracellular parasite nests was observed. At 100 dpi a mild chronic fibrosing myocarditis was detected without parasites in the myocardium. Dystrophin was focally reduced or completely lost in cardiomyocytes at 30 dpi, with the reduction maintained up to 100 dpi. Concurrently, ejection fraction was reduced and the right ventricle was dilated. These findings support the hypothesis that the initial parasitic infection-induced myocardial dystrophin reduction/loss, maintained over time, might be essential to the late development of a cardiomyopathy in mice. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis

Objective: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. Methods: Rats was divided into Control (C), Sham (S), Ischemic-control(IC), Pre-ischemic Hypothermia (IH1), Intra-ischemic Hypothermia (IH2), and Post-ischemic Hypothermia (IH3) groups. Morphometry was performed using the KS400 software (Carl Zeiss (R)) in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. Results: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63). Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03), and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68). Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011), and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79). Conclusion: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

Phenylephrine-induced hypertension during transient middle cerebral artery occlusion alleviates ischemic brain injury in spontaneously hypertensive rats

Arterial hypertension is a major risk factor for ischemic stroke. However, the management of preexisting hypertension is still controversial in the treatment of acute stroke in hypertensive patients. The present study evaluates the influence of preserving hypertension during focal cerebral ischemia on stroke outcome in a rat model of chronic hypertension, the spontaneously hypertensive rats (SHR). Focal cerebral ischemia was induced by transient (1 h) occlusion of the middle cerebral artery, during which mean arterial blood pressure was maintained at normotension (110-120 mm Hg, group 1, n=6) or hypertension (160-170 mm Hg, group 2, n=6) using phenylephrine. T2-, diffusion- and perfusion-weighted MRI were performed serially at five different time points: before and during ischemia, and at 1, 4 and 7 days after ischemia. Lesion volume and brain edema were estimated from apparent diffusion coefficient maps and T2-weighted images. Regional cerebral blood flow (rCBF) was measured within and outside the perfusion deficient lesion and in the corresponding regions of the contralesional hemisphere. Neurological deficits were evaluated after reperfusion. Infarct volume, edema, and neurological deficits were significantly reduced in group 2 vs. group 1. In addition, higher values and rapid restoration of rCBF were observed in group 2, while rCBF in both hemispheres was significantly decreased in group 1. Maintaining preexisting hypertension alleviates ischemic brain injury in SHR by increasing collateral circulation to the ischemic region and allowing rapid restoration of rCBF. The data suggest that maintaining preexisting hypertension is a valuable approach to managing hypertensive patients suffering from acute ischemic stroke. Published by Elsevier B.V.

Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 +/- 9%) than animals with left dominance (7 +/- 5%, P<0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation.

Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

Object. Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. Methods. Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). Results. Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. Conclusions. Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used. (http://thejns.org/doi/abs/10.3171/2011.10.FOCUS11251)

Rest left ventricular function and contractile reserve by dobutamine stress echocardiography in peripartum cardiomyopathy

Aims: To assess whether contractile reserve during dobutamine stress echocardiography (DSE) can predict left ventricular functional recovery in patients with peripartum cardiomyopathy and to assess myocardial fibrosis by magnetic resonance imaging (MRI) in these patients. Methods: Nine patients with peripartum cardiomyopathy were enrolled. All patients underwent DSE and were followed for six months, when a rest Doppler echocardiogram was repeated. MRI was also performed at the beginning of follow-up to identify myocardial fibrosis. Results: Mean age was 29 +/- 7.9 years and mean left ventricular ejection fraction at baseline was 39.4 +/- 8.6% (range 24-49%). Eight of the nine patients showed left ventricular functional recovery with mean ejection fraction at follow-up of 57.1 +/- 13.8%. The ejection fraction response to DSE did not predict recovery at follow-up. On the other hand, left ventricular ejection fraction at baseline correlated with ejection fraction at follow-up. Mild fibrosis was detected in only one patient. Conclusion: Left ventricular ejection fraction at baseline was a predictor of left ventricular functional recovery in patients with peripartum cardiomyopathy. Dobutamine stress echocardiography at presentation of the disease did not predict recovery at follow-up. Myocardial fibrosis appeared to be uncommon in this cardiomyopathy. (C) 2011 Sociedade Portuguesa de Cardiologia Published by Elsevier Espana, S.L. All rights reserved.

Increased levels of Porphyromonas gingivalis are associated with ischemic and hemorrhagic cerebrovascular disease in humans: an in vivo study

Objective: This study investigated the role of periodontal disease in the development of stroke or cerebral infarction in patients by evaluating the clinical periodontal conditions and the subgingival levels of periodontopathogens. Material and Methods: Twenty patients with ischemic (I-CVA) or hemorrhagic (H-CVA) cerebrovascular episodes (test group) and 60 systemically healthy patients (control group) were evaluated for: probing depth, clinical attachment level, bleeding on probing and plaque index. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were both identified and quantified in subgingival plaque samples by conventional and real-time PCR, respectively. Results: The test group showed a significant increase in each of the following parameters: pocket depth, clinical attachment loss, bleeding on probing, plaque index and number of missing teeth when compared to control values (p<0.05, unpaired t-test). Likewise, the test group had increased numbers of sites that were contaminated with P. gingivalis (60%x10%; p<0.001; chi-squared test) and displayed greater prevalence of periodontal disease, with an odds ratio of 48.06 (95% CI: 5.96-387.72; p<0.001). Notably, a positive correlation between probing depth and the levels of P. gingivalis in ischemic stroke was found (r=0.60; p=0.03; Spearman's rank correlation coefficient test). A. actinomycetemcomitans DNA was not detected in any of the groups by conventional or real-time PCR. Conclusions: Stroke patients had deeper pockets, more severe attachment loss, increased bleeding on probing, increased plaque indexes, and in their pockets harbored increased levels of P. gingivalis. These findings suggest that periodontal disease is a risk factor for the development of cerebral hemorrhage or infarction. Early treatment of periodontitis may counteract the development of cerebrovascular episodes.

Educational levels and the functional dependence of ischemic stroke survivors

We evaluated the functional dependence of stroke survivors from the Study of Stroke Mortality and Morbidity, using the Rankin Scale. Out of 355 ischemic stroke survivors (with a mean age of 67.9 years), 40% had some functional dependence at 28 days and 34.4% had some functional dependence at 6 months. Most predictors of physical dependence were identified at 28 days. These predictors were: low levels of education [illiterate vs. >= 8 years of education, multivariate odds ratio (OR) = 3.7; 95% confidence interval (95%CI): 1.60-8.54] and anatomical stroke location (total anterior circulation infarct, OR = 16.9; 95%CI: 2.93-97.49). Low levels of education and ischemic brain injury influenced functional dependence in these stroke survivors. Our findings reinforce the necessity of developing strategies for the rehabilitation of stroke patients, more especially in formulating specific strategies for care and treatment of stroke survivors with low socioeconomic status.

Antiparasitical chemotherapy in Chagas' disease cardiomyopathy: current evidence

Chronic chagasic cardiomyopathy affects 20% of Chagas disease patients. At present, Chagas disease chemotherapy uses nitrofurans, benznidazole (Rochagan (R), Rodanil (R), Roche) or nifurtimox (Lampit (R), Bayer). Treatment during acute and recent chronic phases in childhood effects 71.5% and 57.6%, respectively, of parasitological cure. However, in clinical trials during the late chronic phase, only 5.9% of parasitological cure were achieved. This review focuses on the benefit from aetiological treatment to avoid, stop or revert myocarditis. Divergent data gathered from clinical practice are not convincing to support prescription of aetiological treatment as routine for indeterminate and cardiac chronic patients.

Supine sleep and positional sleep apnea after acute ischemic stroke and intracerebral hemorrhage

OBJECTIVE: Obstructive sleep apnea is frequent during the acute phase of stroke, and it is associated with poorer outcomes. A well-established relationship between supine sleep and obstructive sleep apnea severity exists in non-stroke patients. This study investigated the frequency of supine sleep and positional obstructive sleep apnea in patients with ischemic or hemorrhagic stroke. METHODS: Patients who suffered their first acute stroke, either ischemic or hemorrhagic, were subjected to a full polysomnography, including the continuous monitoring of sleep positions, during the first night after symptom onset. Obstructive sleep apnea severity was measured using the apnea-hypopnea index, and the NIHSS measured stroke severity. RESULTS: We prospectively studied 66 stroke patients. The mean age was 57.6+/-11.5 years, and the mean body mass index was 26.5+/-4.9. Obstructive sleep apnea (apnea-hypopnea index >= 5) was present in 78.8% of patients, and the mean apnea-hypopnea index was 29.7+/-26.6. The majority of subjects (66.7%) spent the entire sleep time in a supine position, and positional obstructive sleep apnea was clearly present in the other 23.1% of cases. A positive correlation was observed between the NIHSS and sleep time in the supine position (r(s) = 0.5; p<0.001). CONCLUSIONS: Prolonged supine positioning during sleep was highly frequent after stroke, and it was related to stroke severity. Positional sleep apnea was observed in one quarter of stroke patients, which was likely underestimated during the acute phase of stroke. The adequate positioning of patients during sleep during the acute phase of stroke may decrease obstructive respiratory events, regardless of the stroke subtype.

Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

Background: Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results: Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2-6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions: Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC.

Myocardial Deformation by Speckle Tracking in Severe Dilated Cardiomyopathy

Background: The high and increasing prevalence of Dilated Cardiomyopathy (DCM) represents a serious public health issue. Novel technologies have been used aiming to improve diagnosis and the therapeutic approach. In this context, speckle tracking echocardiography (STE) uses natural myocardial markers to analyze the systolic deformation of the left ventricle (LV). Objective: Measure the longitudinal transmural global strain (GS) of the LV through STE in patients with severe DCM, comparing the results with normal individuals and with echocardiographic parameters established for the analysis of LV systolic function, in order to validate the method in this population. Methods: Seventy-one patients with severe DCM (53 +/- 12 years, 72% men) and 20 controls (30 +/- 8 years, 45% men) were studied. The following variables were studied: LV volumes and ejection fraction calculated by two and three-dimensional echocardiography, Doppler parameters, Tissue Doppler Imaging systolic and diastolic LV velocities and GS obtained by STE. Results: Compared with controls, LV volumes were higher in the DCM group; however, LVEF and peak E-wave velocity were lower in the latter. The myocardial performance index was higher in the patient group. Tissue Doppler myocardial velocities (S', e', a') were significantly lower and E/e' ratio was higher in the DCM group. GS was decreased in the DCM group (-5.5% +/- 2.3%) when compared with controls (-14.0% +/- 1.8%). Conclusion: In this study, GS was significantly lower in patients with severe DCM, bringing new perspectives for therapeutic approaches in this specific population. (Arq Bras Cardiol 2012;99(3):834-842)

Mechanical thrombectomy with solitaire stent retrieval for acute ischemic stroke in a Brazilian population

OBJECTIVE: Large vessel occlusion in acute ischemic stroke is associated with low recanalization rates under intravenous thrombolysis. We evaluated the safety and efficacy of the Solitaire AB stent in treating acute ischemic stroke. METHODS: Patients presenting with acute ischemic stroke were prospectively evaluated. The neurological outcomes were assessed using the National Institutes of Health Stroke Scale and the modified Rankin Scale. Time was recorded from the symptom onset to the recanalization and procedure time. Recanalization was assessed using the thrombolysis in cerebral infarction score. RESULTS: Twenty-one patients were evaluated. The mean patient age was 65, and the National Institutes of Health Stroke Scale scores ranged from 7 to 28 (average 17+/-6.36) at presentation. The vessel occlusions occurred in the middle cerebral artery (61.9%), distal internal carotid artery (14.3%), tandem carotid occlusion (14.3%), and basilar artery (9.5%). Primary thrombectomy, rescue treatment and a bridging approach represented 66.6%, 28.6%, and 4.8% of the performed procedures, respectively. The mean time from symptom onset to recanalization was 356.5+/-107.8 minutes (range, 80-586 minutes). The mean procedure time was 60.4+/-58.8 minutes (range, 14-240 minutes). The overall recanalization rate (thrombolysis in cerebral infarction scores of 3 or 2b) was 90.4%, and the symptomatic intracranial hemorrhage rate was 14.2%. The National Institutes of Health Stroke Scale scores at discharge ranged from 0 to 25 (average 6.9+/-7). At three months, 61.9% of the patients had a modified Rankin Scale score of 0 to 2, with an overall mortality rate of 9.5%. CONCLUSIONS: Intra-arterial thrombectomy with the Solitaire AB device appears to be safe and effective. Large randomized trials are necessary to confirm the benefits of this approach in acute ischemic stroke.