QT Indexes in Cirrhotic Patients: Relationship with Clinical Variables and Potential Diagnostic Predictive Value.

BACKGROUND AND AIMS: A wide spectrum of cardiovascular changes characterizes cirrhosis, ranging from subclinical alterations to hyperkinetic syndrome. We looked for ECG markers of ventricular repolarization in a population of patients with cirrhosis in comparison to patients without cirrhosis and we investigated the relationship between these and other clinical and laboratory variables. METHODS: In 149 patients with cirrhosis and 152 controls, we measured QT maximum interval (QTmax), QT corrected interval (QTc), QT minimum interval (QTmin), QT dispersion (QTdisp), QT peak and T peak-to-end (TpTe). RESULTS: In subjects with cirrhosis, in comparison with controls, we observed a higher mean QTmax, mean QTc, mean QTmin, mean QTdisp and mean TpTe. At Cox regression analysis, diastolic blood pressure and beta-blocker treatment were significantly associated with mean QTmax, hypertension with mean QTmin and mean QTc, diastolic blood pressure, beta-blockers and ACE-inhibitors/ARBs with QT disp, and beta-blockers with TpTe. Analysis of ROC curves showed a significant area under curve towards cirrhosis diagnosis, respectively, for a cut-off value of > 400 msec of QTmax, > 360 msec of QTmin, > 450 msec of QTc, > 105 msec of TpTe and > 55 msec of QTdisp. CONCLUSIONS: Our study shows that QT indexes are altered in cirrhotic patients and have a potential diagnostic predictive value.

Novel alpha-galactosidase A mutation in a female with recurrent strokes.

Anderson-Fabry disease (AFD) is an X-linked inborn error of glycosphingolipid catabolism resulting from the deficient activity of the lysosomal exoglycohydrolase, a-galactosidase A. The complete genomic and cDNA sequences of the human alpha-galactosidase A gene have been determined and to date, several disease-causing alpha-galactosidase A mutations have been identified, including missense mutations, small deletions/insertions, splice mutations, and large gene rearrangements We report a case of a 56-year-old woman with recurrent cryptogenic strokes. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels. She did not show other typical signs of Fabry disease such as acroparesthesias and angiokeratoma. The patient's alpha-galactosidase A activity was 4.13 nmol/mL/h in whole blood. Alpha-galactosidase A gene sequence analysis revealed a heterozygous single nucleotide point mutation at nucleotide c.550T>A in exon 4 in this woman, leading to the p.Tyr184Asn amino acid substitution.

Single nucleotide polymorphisms (SNPs) of pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes in patients with acute ischemic stroke in relation to TOAST subtype.

BACKGROUND: The genetic basis of complex diseases like ischemic stroke probably consists of several predisposing risk factors, such as genes involved in inflammation and thrombotic pathways. On this basis the aim of our study was to evaluate the role of SNPs (single nucleotide polymorphisms) of some pro-inflammatory/anti-inflammatory and coagulation/fibrinolytic genes in patients with acute ischemic stroke. METHODS: The study population consisted of 144 consecutive Caucasian adult patients who were hospitalized in the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and who met inclusion criteria. The cases were patients admitted with a diagnosis of acute ischemic stroke, and age-matched (± 3 years) control subjects: patients admitted to our Internal Medicine Department for any cause other than acute cardiovascular and cerebrovascular events and for routine checkup examinations. Molecular analysis of alleles at the -308 nucleotide (-308G/A) of TNF-α gene, -1082/-819 haplotypes of IL-10 gene, IL-1RN exon 2 VNR polymorphism, alleles at the -174 nucleotide (-174G/C) of IL-6 gene, PAI-1675 5G/4G polymorphism, alleles at the -7351 nucleotide (-7351C/T) of tPA gene was undertaken in both patient groups. RESULTS: We analyzed 96 subjects with acute ischemic stroke and 48 control subjects. We observed a significantly higher frequency of IL-10 1082 AA genotype in stroke patients with a significant risk trend. We also reported a higher frequency in stroke subjects with a significant risk trend of the TPA 7351-CT genotype and of IL-1RN-VNTR 86 bp 2/2 genotype. Moreover, we observed a significant relationship with TOAST subtype only with regard to CC TPA genotype and 1/1 IL-1 VNTR 86 bp and lacunar strokes. CONCLUSIONS: Ischemic stroke is a common multifactor disease, which is affected by a number of genetic mutations and environmental factors. Our findings showing a relationship between pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes SNPs and ischemic stroke may contribute to delineate a possible stroke risk profile in subjects with cerebrovascular risk factors.

Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke.

UNLABELLED: No study has yet evaluated the relationship between arterial stiffness indexes and immuno-inflammatory pathway in patients with an acute cardiovascular or cerebrovascular event. The aim of our study was to evaluate in patients with acute ischemic stroke the relationship between immune-inflammatory markers and arterial stiffness indexes. METHODS: 107 subjects with acute ischemic stroke and 107 controls without stroke. We evaluated plasma levels of C-reactive protein (CRP), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), von Willebrand Factor (vWF), tissue plasminogen activator (TPA), plasminogen activator inhibitor-1 (PAI-1). Carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) were evaluated. RESULTS: There was a significant positive relationship, corrected for age, and gender, between PWV and CRP, TNF-α, IL1ß, VWF and IL-6. Aix was significantly related to VWF, IL-6 and TNF-α levels. Among Lacunar subtype PWV was significantly related to CRP, IL-1ß, IL-6, TNF-α and vWF. In LAAS subjects PWV was significantly related to CRP, IL-1ß, IL-6, TNF-α but not with vWF. Among CEI subtype, PWV was significantly and positively related to CRP, IL-1ß, TNF-α and vWF. DISCUSSION: Our findings show that both aortic stiffness and wave reflection are related to the degree of systemic inflammation in stroke subjects, suggesting that circulating inflammation mediators can influence the stiffness of vessels distant to those involved in the disease process itself.

Arterial stiffness indexes in acute ischemic stroke: relationship with stroke subtype.

INTRODUCTION: No study has evaluated both arterial stiffness indexes (PWV and Aix) in patients with an acute cerebrovascular event. The aim of our study was to evaluate arterial stiffness indexes in subjects with acute ischemic stroke and to evaluate the relationship between these indexes and other clinical and laboratory variables. MATERIALS AND METHODS: We enrolled all consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2006 and January 2009, and hospitalized control patients without a diagnosis of acute ischemic stroke. The type of acute ischemic stroke was classified according to the TOAST classification. Carotid-femoral pulse wave velocity (PWV) was evaluated by Applanation tonometry (SphygmoCor) and the aortic pressure waveform was used to calculate the Augmentation index (Aix). RESULTS: We enrolled 107 patients with acute ischemic stroke and 102 control subjects matched for age, sex, cardiovascular risk factors and previous cardiovascular morbidity. Stroke patients, compared to subjects without acute ischemic stroke, showed a higher mean Aix (103+/-3.5 mmHg vs. 99+/-4.6 mmHg) and PWV (11.8+/-3.3 m/s vs. 10.02+/-2.29 m/s). Augmentation Index and PWV values in lacunar subjects were significantly higher compared to values observed in LAAS, CEI and subtypes. DISCUSSION: Our study shows that patients with acute ischemic stroke show higher arterial stiffness index values. Among stroke patients, lacunar subtype has the highest arterial stiffness indexes. This finding underlines previous data regarding the strict association between hypertension and diabetes and arterial stiffness, owing the higher percentage of hypertensive and diabetic subjects in the lacunar group.

Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: relationship with TOAST subtype, outcome and infarct site.

BACKGROUND: The aim of our study was to evaluate in patients with acute ischemic stroke the relationship between immuno-inflammatory variables, clinical outcome and infarct site. MATERIALS AND METHODS: We evaluated plasma levels of IL-1beta, TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1 ,sVCAM-1 vWF, TPA and PAI-1. RESULTS: Patients with cardioembolic subtype showed significantly higher median plasma levels of TNF-alpha, IL-6, IL-1beta whereas the lacunar subtype showed significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. CONCLUSIONS: A significant association was noted between the severity of neurological deficit at admission, the diagnostic subtype and some inflammatory variables.