Maria Kosmidou

Is Vertebral Artery Hypoplasia a Predisposing Factor for Posterior Circulation Cerebral Ischemic Events? A Comprehensive Review

Vertebral artery hypoplasia is not currently considered an independent risk factor for stroke. Emerging evidence suggest that vertebral artery hypoplasia may contribute to posterior circulation ischemic events, especially when other risk factors coexist. In the present literature review, we present published data to discuss the relationship between a hypoplastic vertebral artery and posterior circulation cerebral ischemia. Despite difficulties and controversies in the accurate definition and prevalence estimation of vertebral artery hypoplasia, ultrasound studies reveal that the reduced blood flow observed ipsilateral to the hypoplastic vertebral artery may result in local cerebral hypoperfusion and subsequent focal neurological symptomatology. That risk of cerebral ischemia is related to the severity of the hypoplasia, suggesting that the smaller of paired arteries are more vulnerable to occlusion. Existing cohort studies further support clinical observations that hypoplastic vertebral artery enhances synergistically the vascular risk for posterior circulation ischemic events and is closely associated with both atherosclerotic and prothrombotic processes.

Complex Atheromatous Plaques in the Descending Aorta and the Risk of Stroke: A Systematic Review and Meta-Analysis

Background and Purpose— Proximal aortic plaques, especially in the aortic arch, have already been established as an important cause of stroke and peripheral embolism. However, aortic plaques situated in the descending thoracic aorta have recently been postulated as a potential embolic source in patients with cryptogenic cerebral infarction through retrograde aortic flow. The aim of the present study was to evaluate the potential association of descending aorta atheromatosis with cerebral ischemia. Methods— We conducted a systematic review and meta-analysis of all available prospective observational studies reporting the prevalence of complex atheromatous plaques in the descending aorta in patients with stroke and in unselected populations undergoing examination with transesophageal echocardiography. Results— We identified 11 eligible studies including a total of 4000 patients (667 patients with stroke and 3333 unselected individuals; mean age, 65 years; 55% men). On baseline transesophageal echocardiograpic examination, the prevalence of complex atheromatous plaques in the descending aorta was higher (P=0.001) in patients with stroke (25.4%; 95% confidence interval, 14.6–40.4%) compared with unselected individuals (6.1%; 95% confidence interval, 3.4–10%). However, no significant difference (P=0.059) in the prevalence of complex atheromatous plaques in the descending aorta was found between patients with cryptogenic (21.8%; 95% confidence interval, 17.5–26.9%) and unclassified (28.3%; 95% confidence interval, 23.9–33.1%) cerebral infarction. Conclusions— Our findings indicate that the presence of complex plaques in the descending aorta is presumably a marker of generalized atherosclerosis and high vascular risk. The present analyses do not provide any further evidence for a direct causal relationship between descending aorta atherosclerosis and cerebral embolism.

Lateral medullary ischaemic events in young adults with hypoplastic vertebral artery

Objective: To present three cases of young adults with lateral medullary ischaemic events associated with a hypoplastic vertebral artery (VA). All three patients had two additional atherosclerotic or non-atherosclerotic risk factors for stroke. Patients and methods: One female, aged 40 years, and two males, aged 38 and 37 years, each with two risk factors for stroke, presented to the emergency department with acute onset of symptoms and findings consistent with lateral medullary syndrome. All three patients underwent emergency CT scan of the brain followed by MRI and magnetic resonance angiography (MRA). Results: The CT scans were negative in all patients. MRI revealed a lateral medullary lesion in only one patient. All three patients had a hypoplastic VA ipsilateral to the clinical ischaemic event on MRA. Conclusions: Hypoplasia of VA is not considered a risk factor for stroke as it is a common variant in up to 75% of the general population. However, in our patients, hypoplastic VA coexisted with two risk factors and resulted in stroke. Thus although a hypoplastic VA may not be an uncommon asymptomatic finding, it may contribute to stroke if additional risk factors are present.

Patient compliance with SSRIs and gabapentin in painful diabetic neuropathy.

BackgroundAnticonvulsants are widely used for treatment of painful diabetic neuropathy. Selective serotonin reuptake inhibitors (SSRIs) are not first-line drugs but are commonly prescribed medicines for chronic pain. The majority of patients are hesitant to use these drug groups, thus their compliance remains an issue. ObjectiveTo compare patient compliance and the effectiveness of 2 SSRIs (paroxetine or citalopram) and 1 anticonvulsant (gabapentin) in patients with painful diabetic neuropathy. MethodsThis was a 6 months prospective trial in 101 patients with painful diabetic neuropathy and minimum score of 2 on a pain intensity scale ranging of 0 to 4. Compliance was assessed with patient interviews and pill counts. Adverse events, early discontinuation or satisfaction with treatment were also evaluated. ResultsPatients receiving SSRIs reported greater satisfaction and fewer concerns of the side-effects with their treatment (P<0.05) compared with the patients taking gabapentin. There was statistically significant better mood in the SSRI group (P<0.05). Overall, 43.5% of those taking SSRIs noticed no effect on the pain control, 50% felt better, and 6.5% felt worse. Among the patients taking gabapentin, 51% felt better, 40.5% noticed no effect, and 8.5% felt worse. Finally, on the pill count, more patients on SSRIs (93.5%) than on gabapentin (82.9%) were taking over the 75% of their medication (P<0.05). ConclusionsThe lack of negative effects on quality of life, the better compliance, and the comparable efficiency of SSRIs suggest that these drugs may be considered as alternative to gabapentin in painful diabetic neuropathy.

Effects of Atorvastatin on Red-blood Cell Na+/Li+ Countertransport in Hyperlipidemic Patients With and Without Hypertension

BACKGROUNDnTo explore the effect of short-term cholesterol-lowering treatment with atorvastatin on erythrocyte sodium-lithium countertransport (Na(+)/Li(+) CT) activity.nnnMETHODSnGroup A consisted of 30 patients (14 men) with mild essential hypertension (systolic blood pressure (SBP), 140-159 mm Hg and/or diastolic BP, 90-99 mm Hg) and primary hypercholesterolemia low-density lipoprotein (LDL) cholesterol >4.1 mmol/l and triglycerides (TG) <2.8 mmol/l), group B of 30 normotensive patients (16 men) with primary hypercholesterolemia, while 37 (18 men) healthy volunteers comprised the control group. After a 6-week dietary lead-in, all eligible patients were prescribed 20 mg/day of atorvastatin. Anthropometric data, blood-pressure (BP) measurements and determinations of lipid, non-lipid metabolic parameters (including homeostasis model assessment index, (HOMA-IR)) and erythrocyte Na(+)/Li(+) CT activity were collected at baseline and after 12 weeks of treatment.nnnRESULTSnAt baseline Na(+)/Li(+) CT activity was significantly higher in group A and B compared with the control group and correlated directly with obesity indices, systolic and diastolic BP, total cholesterol, LDL-cholesterol, TG, apolipoprotein B (apoB), HOMA-IR, uric acid and inversely with high-density lipoprotein (HDL)-cholesterol and apoA1. Systolic and diastolic BP levels, HOMA-IR and Na(+)/Li(+) CT activity were significantly decreased after atorvastatin treatment in both patient groups. The reduction in Na(+)/Li(+) CT activity correlated with baseline Na(+)/Li(+) CT activity and the changes in HOMA-IR values.nnnCONCLUSIONSnShort-term treatment with atorvastatin for patients with hypercholesterolemia, and with or without essential hypertension, is associated with a significant reduction in the erythrocyte Na(+)/Li(+) CT activity, BP levels and insulin resistance independent of concomitant changes in lipid parameters.

Measurements of endothelin-1, C-reactive protein and fibrinogen plasma levels in patients with acute ischemic stroke

Abstract Objective: To assess plasma endothelin-1 (ET-1), C-reactive protein (CRP) and fibrinogen (FIB) levels in acute ischemic stroke (AIS) and explore the potential association among them. Methods: In 23 consecutive patients with AIS diagnosed clinically and confirmed by CT brain scan, we measured plasma levels of ET-1 by radioimmunoassay, and CRP and FIB on the first and fifth days after the onset of AIS and we compared them with the levels of ten healthy volunteers in the control group. Results: The mean plasma levels of ET-1 in AIS patients on the first and fifth days were respectively 19.93 ± 6.72 and 16.47 ± 26.3 pmol/l (p<0.001) compared with 3.68 ± 1.2 pmol/l in the control group (p<0.001 versus mean values on the first and fifth days). The mean plasma levels of CRP in the patients on the first and fifth days were respectively 2.7 ± 4.7 and 3.0 ± 4.4 mg/dl (p>0.05) compared with 0.2 ± 0.1 mg/dl in the control group (p<0.05 versus mean values on the first and fifth days). The mean plasma levels of FIB in the patients on the first and fifth days were respectively 361 ± 98.89 and 392.7 ± 144.89 mg/dl, while in the control group, it was 330.5 ± 90.28 mg/dl (p>0.05 versus mean values on the first and fifth days). A positive association was found between the plasma levels of ET-1 and CRP on the fifth day (p<0.05). Conclusions: ET-1 was found to be significantly elevated in the plasma in the AIS. There is association between ET-1 and CRP on the fifth day after AIS. Plasma levels of ET-1 and its association with CRP levels may be used as additional biomarkers for AIS.

An association study between catalase -262C > T gene polymorphism, sodium-lithium countertrasport activity, insulin resistance, blood lipid parameters and their response to atorvastatin, in Greek dyslipidaemic patients and normolipidaemic controls

This study attempted to examine the effect of a functional catalase gene polymorphism, CAT -262C>T, on sodium-lithium countertransport (Na-Li CT) activity, insulin resistance determined as the homeostasis model assessment index (HOMA-IR), blood lipid parameters (cholesterol, triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apolipoprotein B, apolipoprotein A-I) and their response to atorvastatin, in previously characterized Greek dyslipidaemic patients and normolipidaemic controls. Putative associations were examined by running univariate analyses with a general linear model, using age, sex, smoking and hypertension as covariates. While no statistically significant associations were detected between the CAT -262C>T polymorphism and either baseline values or their modulation by atorvastatin in the patient group, HOMA-IR values were significantly (p=0.028) lower among CAT -262CC controls compared to their T allele carrier counterparts. A trend towards higher plasma triglyceride values among CAT -262CC genotypes was also detected, in both dyslipidaemic patients and normolipidaemic controls.

Glutathione S‐Transferase Null and Cholesteryl Ester Transfer Protein TaqI B Polymorphisms and Lipid Response to Atorvastatin in Greek Dyslipidaemic Patients

Impairment of high-density lipoprotein (HDL) cholesterolefflux capacity, coupled to attenuated antioxidative andanti-inflammatory properties of HDL particles, has beenlately recognized as intimately connected to atherogenicdyslipidaemia, a well-established cardiovascular risk factor[1]. Concomitantly, raising HDL-cholesterol (HDL-C) andapolipoprotein A-I (apoA-I) levels has been proposed as amajor anti-atherogenic therapeutic target [2]. While 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA)reductase inhibitors (statins) are very efficacious in reducingtotal cholesterol, triacylglycerol, low-density lipoproteincholesterol (LDL-C) and apolipoprotein B (apoB) levels indyslipidaemic patients, their effect on HDL-C and apoA-I ismoderate at best, and may be dependent on the type ofstatin used, dosage, duration of treatment, but also, geneticfactors [3,4]. In the past, pharmacogenetic studies of lipidresponse to statins have focused almost exclusively on poly-morphisms of genes related to lipoprotein turnover, with thegene coding for cholesteryl ester transfer protein (CETP)receiving most of the attention [5–7]. Other factors may beinvolved as well. Oxidative stress has been implicated in thepathophysiology of cardiovascular disease [8] and oxidativemodification has been recently reported to impair thelipid-binding capacity of apoA-I, resulting in reduced HDLcholesterol efflux [9]. In addition, the apoA-I gene promoteris known to contain an antioxidant response element andmay be responsive to oxidative stress [10]. Because statins arereportedly able to attenuate the production of reactiveoxygen species through mechanisms unrelated to theirlipid-lowering effect [11], the possibility that genes affectingthe antioxidant status of the organism can influence apoA-Iresponse to these drugs is an intriguing and as yet untestedhypothesis. On the other hand, such an effect could con-ceivably be modulated by polymorphisms affecting reversecholesterol transport – such as CETP TaqI B – especiallysince a growing body of evidence, from human and animalstudies, suggests that there is a functional interactionbetween apoA-I expression and CETP activity [12–14].Glutathione S-transferases (GST) are phase II biotrans-formation enzymes that play a major role in the antioxidantcapability of the organism, by catalysing the conjugation ofreduced GSH to a variety of endogenous and exogenoussubstrates [15]. Two common deletion polymorphisms ofthe GST T1 and M1 genes, resulting in complete absence ofactivity of the respected enzymes (null genotypes), haverecently become the focus of studies investigating their effecton the risk for myocardial infarction [16,17], vascularinflammation [18], hypertension [19] and smoking-relatedcardiovascular disease [20–23].In undertaking this study, we hypothesized that genotypingfor the GST T1 and M1 null, as well as the TaqI B poly-morphisms, may assist in the identification of strongerresponders to atorvastatin treatment, especially with respectto apoA-I and HDL-C levels that are only modestly affectedby this drug. Our study group consisted of 55 previouslyuntreated, Greek consecutive dyslipidaemic [total cholesterol(CHOL) > 240 mg/dl, LDL-C > 160 mg/dl and triacylglycerols(TG) < 250 mg/dl] patients. The latter were all examined in theoutpatient clinic of the First Propedeutic Clinic of AHEPAUniversity Hospital, Thessaloniki, Greece, from November2004 until May 2006. Exclusion criteria included: damage oftarget organs (coronary disease ruled out based on symptoms,electrocardiogram and history, renal failure, retinopathyand stroke), history of diabetes mellitus, hypothyroidismand impaired hepatic or renal function (fig. 1). During therun-in period (4–6 weeks), all patients underwent a completeclinical and laboratory examination to exclude secondary

Patient compliance with neuropathic pain treatment.

We read with great interest the article by Gordh et al. [4] concerning the efficacy and safety of gabapentin in the treatment of traumatic nerve injury pain. In this study, the authors concluded that gabapentin was not statistically significantly superior to placebo for the primary outcome measure of change in weekly mean pain intensity score. On the other hand, gabapentin improved the quality of life and sleep. Additionally, the authors reported suspected non-compliance in 5 patients, and defined non-compliance in 22 of 120 (18.3%) randomized patients [4]. We congratulate the authors for reporting this thoughtful study on pharmaceutical management of traumatic nerve injury pain. We think that this study raises important questions concerning compliance with gabapentin or generally with analgesic treatment: First, how do we define compliance to treatment? Second, is compliance a numeric or qualitative factor? Third, does compliance to medication in chronic pain improves the quality of life? In order to define compliance in this study, Gordh et al. [4] used the same numeric rationale of at least 75% intake of scheduled dosages, as we did in a previous study that compared compliance with gabapentin versus SSRIs in painful diabetic neuropathy [2]. Interestingly, in our study we observed a similar percentage (17.9%) of non-compliant patients with gabapentin [2], suggesting a common attitude towards this drug in pain patients worldwide. Gordh et al. [4] reported the detailed information of withdrawn patients from the study and adverse events while the patients’ quality of life was measured with the SF-36 [6] showing that the medication improved significantly the vitality, but not the other important parameters as role-emotional and mental health [4]. Additionally, statistically significantly more patients on gabapentin treatment than on placebo improved in the Clinician and Patient Global Impression of Change, suggesting the need of the medication [4]. The successful management of chronic pain is a health care priority, and the most difficult to manage is neuropathic pain leading to decreased home and work productivity and high anxiety and depression [5]. To our opinion, medication compliance is of great importance for pain management. The consequences of non-compliance include poor patient health, discomfort to patient, further expensive diagnostic testing, lack of effectiveness of health care and deterioration of the doctor–patient relationship [3]. A previous study has found that only 68% of patients treated for chronic non-malignant pain are compliant with their therapeutic regimen [1]. More studies should focus in compliance and in development of well tolerated analgesic treatments in order to have direct comparisons of effective drugs for successful management of pain.

An association study of sodium-lithium countertransport activity with glutathione S transferase (GST) T1 and GST M1 null polymorphisms in Greek dyslipidaemic patients and controls.

Abstract Background: Previous genomic linkage studies have produced evidence linking sodium-lithium countertransport activity (Na/Li CT) with various chromosomal regions including loci harbouring glutathione S transferase (GST) genes. The aim of this study was to examine the putative association of erythrocyte Na/Li CT activity with GST T1 and M1 gene null polymorphisms. Methods: Na/Li CT activity was determined in erythrocytes isolated from 85 individuals, using a standard assay procedure employing atomic absorption spectroscopy. Genotyping of the GST T1 and GST M1 null polymorphisms was accomplished with a multiplex PCR method. A general linear model using age, sex, smoking, dyslipidaemia and hypertension as covariates was used to examine the association of Na/Li CT activity with the GST T1 and GST M1 genotypes. Results: Individuals with the GST T1 null genotype displayed marginally significantly (p=0.049) lower values of Na/Li CT activity compared to those harbouring at least one copy of the GST T1 gene. The significance of this association was eliminated following adjustment for covariates (p=0.150), but survived as a trend when the sample was limited to normotensive and normolipidaemic individuals (p=0.070). No association was detected between the GST M1 null polymorphism and Na/Li CT activity. Conclusions: The suggestive association of the GST T1 null polymorphism with erythrocyte Na/Li CT activity is in line with previously published data from genetic linkage and biochemical analyses and may be of potential prognostic value as regards the behaviour of the countertransport and the development of related pathologies under conditions of oxidative insult. Clin Chem Lab Med 2008;46:306–10.