Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety.

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

[Advanced Parkinson's disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]. / Az elôrehaladott Parkinson-kór jellemzôi a klinikai gyakorlatban: az OBSERVE-PD vizsgálat eredményei és a magyarországi alcsoport elemzése.

BACKGROUND AND PURPOSE: The majority of patients with advanced Parkinson's disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson's disease; the proportion of Parkinson's patients with advanced Parkinson's disease, the referral process, and the clinical features used to characterize advanced Parkinson's disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson's patients identified as advanced patients according to physician's judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. METHODS: The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson's disease status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson's disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. RESULTS: Overall, 2627 patients with Parkinson's disease from 126 sites were documented. In Hungary, 100 patients with Parkinson's disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson's disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson's disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). CONCLUSION: Physicians in Hungarian movement disorder centers assessed that half of the Parkinson's patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson's disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.

[Angioneuritic edema in ischaemic stroke patients treated with rt-PA]. / Angioneuroticus oedema elofordulása ischaemiás stroke miatt rt-PA-val kezelt betegekben.

Data of our 254 patients who were treated with rt-PA between 1st of Jan, 2011 and 31st of Dec, 2014 were processed. We focused on angioneurotic oedema as allergic complication of thrombolysis which caused life threatening respiratory obstruction in two cases. We describe these two patients' history. Out of 254 patients six (2.3%) suffered angioneurotic edema caused respiratory obstruction in two (0.90%) cases. This occurrence is approximately 1.3-5.1% in literature. Five, out of six patients who suffered from angioneurotic oedema, had been treated with ACE inhibitors or ARB before. The role of ACE inhibitors is known in metabolism of bradykinin cascade. Plasmin which present during thrombolysis, precipitates biochemical mechanisms of this potential life threatening complication. Therefore rt-PA alone can be the cause of angioedema, but it can be more frequent together with ACE inhibitors therapy.

[Effectiveness of anticoagulation with vitamin K antagonists in acute stroke patients with atrial fibrillation--Hungarian results]. / K-vitamin-antagonisták altal biztosított antikoaguláció eredményessége pitvarfibrillációban szenvedo akut stroke-betegek körében--hazai tapasztalatok.

BACKGROUND AND OBJECTIVE: An estimated 20% of ischemic strokes are of cardiogenic origin, half of which is associated with atrial fibrillation (AF). Anticoagulation treatment of patients with this arrhythmia reduces their risk of stroke. Effectiveness and safety of oral anticoagulant therapy with vitamin K antagonists (VKA) is limited, however, by their well-known narrow therapeutic window and the substantial inter- and intraindividual variability of INR values depending on genetic and dietary factors as well as drug interactions. Our objective was to evaluate the prevalence of adequate anticoagulation and the level of anticoagulant effect actually achieved among patients with AF hospitalized for acute stroke. METHODS: Patients with AF admitted to our hospital ward in 2012 for acute stroke (n = 226) were included in the analysis. Using descriptive statistics, relevant clinical and therapeutic characteristics of the patients were assessed, with special reference to the INR values on admission (among patients with known AF), and the clinical outcomes. RESULTS: Of the study cohort, 170 patients had a diagnosis of AF before the admission for stroke, but 47% of them did not take anticoagulants. Patients who suffered stroke while on anticoagulants (83 on VKA, 7 on low-molecular-weight heparins), were in most cases (75%) out of the therapeutic INR range, typically undertreated (INR < 2). Overall, inadequate or completely absent anticoagulation was documented in 81% of the stroke cases occurring in patients with known AF. Of the entire study cohort, 41% was discharged home, 34% required continued institutional care, and 25% died. CONCLUSIONS: The inadequacy or lack of anticoagulation was observed in the vast majority of acute strokes in patients with known AF. These cases are often related to the well-documented limitations of VKA therapy in terms of its safety, tolerability and/or practical aspects. To prevent them, important changes are warranted in the anticoagulation practice, including the closer control of VKA therapy and the broader use of new oral anticoagulants.

[Experience with levodopa/carbidopa intestinal gel in the treatment of advanced Parkinson's disease in Hungary]. / A levodopa/carbidopa intestinalis gél kezelés magyarországi tapasztalatai elorehaladott Parkinson-kórban.

In the advanced Parkison's disease (PD) the late complications of levodopa therapy have to be considered: motor and/or non-motor fluctuations with or without disturbing dyskinesias. The non-motor fluctuations often influence the quality of life (QoL) in a much more negative way compared with the motor symptoms. In the treatment of advanced PD there are several device-aided methods - deep brain stimulation, apomorphine pump, levodopa/carbidopa intestinal gel (LCIG) - to improve the symptoms, the QoL, sometimes even in an individual, tailored custom form. The LCIG therapy was introduced in Hungary in 2011. Here we summarize the data of our patients: we have tested almost 60 patients and in 43 cases we have started this treatment. We analyze the duration of illness, levodopa therapy, motor and non-motor fluctuation of patients and present our experiences with the test phase and the chronic LCIG therapy via PEG/PEJ implantation. We paid attention to the surgery and device - depending side effects. Our experiences are similar to the international data. In patients selection ,,the right treatment, to the right patient, in the right time" is of importance.

[Study of the effects of vinpocetin on cognitive functions]. / A vinpocetin kognitív funkciókra gyakorolt hatásának vizsgálata.

INTRODUCTION: Chronic cerebral hypoperfusion is a risk factor for the development of certain types of dementia. Mild cognitive impairment is a stage of predementia condition, because the symptoms are similar but not as severe as the symptoms in patients with dementia. Vinpocetine, due to its complex mechanism of action, has an important role in the improvement of chronic cerebral hypoperfusion. OBJECTIVES: The aim of our study was to determine the severity of the cognitive decline and to investigate the efficacy and safety of per os 18 months vinpocetine treatment in patients with mild cognitive impairment. METHODS: We used psychometrical tests (MMSE, ADAS-Cog) to assess the cognitive functions. CGIC-PGIC was used to evaluate the overall change in the disease status. ADL was used to assess the patient's daily activity and the Hamilton Depression Scale to evaluate the patient's mood. The assessments were performed at six visits during the 18 months treatment period. RESULTS: At the beginning of the treatment, the stage of our patients' mild cognitive impairment was moderately severe. Significant improvement was detected in the psychometrical tests after the 18 months treatment period. The overall status of the disease improved significantly according both to the patient and the investigator. Also significant improvement was detected in daily activity. The complex improvement of the clinical symptoms affected the patients' mood positively. Moreover, vinpocetine was safe and had a good tolerability during the whole study period. CONCLUSIONS: Vinpocetine, due its complex mechanism of action, improved significantly the cognitive functions, overall disease status and quality of life in patients with chronic cerebral hypoperfusion. As a result, vinpocetine treatment can be recommended for patients with mild cognitive impairment.

A8344G mutation of the mitochondrial DNA with typical mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome.

We report an unusual case of juvenile ischaemic stroke syndrome associated with the A8344G mutation in tRNA(Lys) gene of mitochondrial DNA. The clinical phenotype of patient was typical for MELAS (mitochondrial ecephalomyapathy with lactate acidosis and stroke like episodes). The MELAS has been related to mutation A3243G in most cases, but some other mitochondrial DNA mutations were described in the background of this syndrome as well. A 22-years-old man and his family were investigated. Throughout clinical investigation as well as Doppler sonography, neuroradiological, and immunserological examinations were performed. Molecular studies included the analysis of the Leiden, prothrombin G20210A and the most common mitochondrial DNA mutations. The DNA analysis of the proband revealed a heteroplasmic A8344G substitution in the T-loop of the tRNALYS gene. The mutation could not been detected in her mother blood. We can conclude that A8344G mutation of the mitochondrial DNA resulted in juvenile ischemic stroke, which is associated only rarely to this genetic alteration. In young age onset of a stroke-like episode with undetermined etiology the mtDNA alterations always have to be excluded.

Implant for Augmentation of Cerebral Blood Flow Trial-1 (ImpACT-1). A single-arm feasibility study evaluating the safety and potential benefit of the Ischemic Stroke System for treatment of acute ischemic stroke.

BACKGROUND: The Ischemic Stroke System is a novel device designed to deliver stimulation to the sphenopalatine ganglion(SPG).The SPG sends parasympathetic innervations to the anterior cerebral circulation. In rat stroke models, SPG stimulation results in increased cerebral blood flow, reduced infarct volume, protects the blood brain barrier, and improved neurological outcome. We present here the results of a prospective, multinational, single-arm, feasibility study designed to assess the safety, tolerability, and potential benefit of SPG stimulation inpatients with acute ischemic stroke(AIS). METHODS: Patients with anterior AIS, baseline NIHSS 7-20 and ability to initiate treatment within 24h from stroke onset, were implanted and treated with the SPG stimulation. Patients were followed up for 90 days. Effect was assessed by comparing the patient outcome to a matched population from the NINDS rt-PA trial placebo patients. RESULTS: Ninety-eight patients were enrolled (mean age 57years, mean baseline NIHSS 12 and mean treatment time from stroke onset 19h). The observed mortality rate(12.2%), serious adverse events (SAE)incidence(23.5%) and nature of SAE were within the expected range for the population. The modified intention to treat cohort consisted of 84 patients who were compared to matched patients from the NINDS placebo arm. Patients treated with SPG stimulation had an average mRS lower by 0.76 than the historical controls(CMH test p = 0.001). CONCLUSION: The implantation procedure and the SPG stimulation, initiated within 24hr from stroke onset, are feasible, safe, and tolerable. The results call for a follow-up randomized trial (funded by BrainsGate; clinicaltrials.gov number, NCT03733236).

Association between human paraoxonase 1 activity and intima-media thickness in subjects under 55 years of age with carotid artery disease.

BACKGROUND: Human serum paraoxonase (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (oxLDL); therefore, it may protect against atherosclerosis. PON1 activity and polymorphisms have been inconsistently associated with carotid artery disease. The goal of this study was to clarify the role of PON1 activity and phenotype on carotid artery disease and its correlation with some inflammatory and immune markers in subjects under 55 years with early-onset carotid atherosclerosis. METHODS: Sixty patients with occlusive carotid artery disease and 30 healthy controls were enrolled. Intima-media thickness (IMT) was measured by high-resolution ultrasound of both common carotid arteries. Anti-oxLDL antibody levels were determined by ELISA. RESULTS: In the whole study population we found a negative correlation between PON1 activity and IMT (r = -0.27, p = 0.011), and between salt-stimulated PON1 activity and IMT (r = -0.24, p = 0.02). Both PON1 activity and salt-stimulated PON1 activity negatively correlated with anti-oxLDL levels (r = -0.28, p = 0.008; r = -0.26, p = 0.01). PON1 activity was lower in patients compared to controls; however, the difference was not significant.PON1 phenotype distribution of patients and controls did not differ significantly. CONCLUSION: The importance of PON1 activity as a predictive risk factor for early-onset occlusive carotid artery disease should be assessed in future studies.

Dimethylarginines at the crossroad of insulin resistance and atherosclerosis.

We tested if asymmetric dimethylarginine (ADMA) contributes to the simultaneous evolution of atherosclerosis and insulin resistance. We investigated the significant predictors of insulin resistance in the context of atherosclerosis, focusing on the role ADMA, symmetric dimethylarginine (SDMA), and l-arginine play in a cohort of young atherosclerotic patients and their age-matched controls. In a case-control study, 60 patients younger than 55 years having at least 30% stenosis of the internal carotid artery and 30 age- and sex-matched controls were recruited at a community-based neurosonologic laboratory. We found a strong positive association between the homeostasis model assessment of beta-cell function and insulin resistance and the ADMA/SDMA ratio that remained statistically significant even after adjusting for all significant and a priori identified determinants (beta = 6.76; 95% confidence interval [CI], 2.13-11.39; P = .005). Interestingly, this relationship was even more pronounced in the atherosclerotic stratum (beta = 8.29; 95% CI, 1.43-15.15; P = .019), whereas, on multiple linear regression, lack of association was seen in subjects free of carotid atherosclerosis (beta = 1.39; 95% CI, -5.46 to 8.26; P = .671). We conclude that ADMA/SDMA ratio is a significant determinant of insulin resistance and may be a better parameter to monitor than ADMA alone. By accounting for the competition at the y+ transporters, ADMA/SDMA ratio could be an indicator of intracellular ADMA level.

[Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions]. / A vinpocetin agyi véráramlásra és kognitív funkciókra gyakorolt hatásának vizsgálata.

INTRODUCTION: Vinpocetine has been widely used in the treatment of ischaemic cerebrovascular diseases and dementias of vascular type. Chronic cerebral hypoperfusion plays an important role in the development of certain types of dementia. In consequence of complex mode of action vinpocetine plays a significant role in the improvement of cerebral hypoperfusion. The symptoms of mild cognitive impairment considered as "predementia" are similar to those of dementia, although milder. AIMS: The authors investigated the characteristics of the blood flow parameters of patients with ischemic stroke and mild cognitive impairment both in resting conditions or following chemical stimulus as well as they investigated the severity of mental deterioration in the two patient groups. In a pilot study the authors examined the influence of 12-week long oral vinpocetine therapy on the blood flow parameters and cognitive functions in the two patient groups. METHODS: The authors studied the blood flow velocity of a. cerebri media in resting conditions and after 30 sec of breath holding with transcranial Doppler before treatment and after a 12-week long oral vinpocetine treatment. At the same time psychometric tests (MMSE, ADAS-Cog) were used in order to examine cognitive functions, while the general condition of the patients were scored by Clinical Global Impression (CGI) scale. RESULTS: After a 12-week long oral vinpocetine treatment the increase of blood flow velocity in resting conditions compared to the baseline values was significant in the vascular group. The percent increase of mean velocity after the breath holding TCD test showed a significant increase compared to the baseline in both patient groups. The authors found a significant improvement of cognitive functions after a 12-week long oral vinpocetine therapy using psychometric tests. The improvement was identical in both groups. The general condition of patients improved significantly according to both the investigator's and the patients' opinion; patients with mild cognitive impairment judged the improvement higher. CONCLUSIONS: Vinpocetine improved the cerebrovascular reserve capacity in both patient groups and favourably influenced the cognitive status and general condition of patients with chronic hypoperfusion. The authors recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.

Assessment of intracranial vessels in association with carotid atherosclerosis and brain vascular lesions in rheumatoid arthritis.

BACKGROUND: Stroke has been associated with rheumatoid arthritis (RA). We assessed patients with RA and healthy control subjects by transcranial Doppler (TCD), carotid ultrasonography and brain magnetic resonance imaging (MRI). METHODS: Altogether, 41 female patients with RA undergoing methotrexate (MTX) or biologic treatment and 60 age-matched control subjects underwent TCD assessment of the middle cerebral artery (MCA) and basilar artery. Pulsatility index (PI), resistivity (resistance) index (RI) and circulatory reserve capacity (CRC) were determined at rest (r) and after apnoea (a) and hyperventilation (h). The presence of carotid plaques and carotid intima-media thickness (cIMT) were also determined. Intracerebral vascular lesions were investigated by brain MRI. RESULTS: MCA PI and RI values at rest and after apnoea were significantly increased in the total and MTX-treated RA populations vs control subjects. MCA CRC was also impaired, and basilar artery PI was higher in RA. More patients with RA had carotid plaques and increased cIMT. Linear regression analysis revealed that left PI(r) and RI(r) correlated with disease duration and that left PI(r), RI(r), PI(a), PI(h) and basilar PI correlated with disease activity. Right CRC inversely correlated with 28-joint Disease Activity Score. Disease activity was an independent determinant of left PI(a) and right CRC. Compared with long-term MTX treatment alone, the use of biologics in combination with MTX was associated with less impaired cerebral circulation. Impaired cerebral circulation was also associated with measures of carotid atherosclerosis. CONCLUSIONS: To our knowledge, this is the first study to show increased distal MCA and basilar artery occlusion in RA as determined by TCD. Patients with RA also had CRC defects. We also confirmed increased carotid plaque formation and increased cIMT. Biologics may beneficially influence some parameters in the intracranial vessels.

Serum levels of platelet released CD40 ligand are increased in early onset occlusive carotid artery disease.

OBJECTIVE: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls. METHODS: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age-matched controls using ELISA. Degree of stenosis of the internal carotid artery (ICA), and intima-media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean +/- SD. RESULTS: Mean age was 50.9 +/- 3.5 and 50.1 +/- 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 +/- 0.14 vs. 0.78 +/-0.12 mm, p=0.0003). Serum levels of sCD40L were significantly higher (6.9 +/- 5 vs. 4.5 +/- 3.0 ng/mL, p=0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 +/- 56.9 vs. 79.3 +/- 18.7 pg/mL, p=0.34). IMT did not correlate with sCD40L or sCD40 levels (R=-0.03, p=0.77; and R=0.109, p=0.308, respectively). CONCLUSIONS: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis.

Changes of cerebral hemodynamics in hypertensives during physical exercise.

BACKGROUND AND PURPOSE: Previously, 30 untreated hypertensive patients were investigated by transcranial Doppler (TCD) monitoring during physical exercise, and changes of hemodynamic parameters were compared with those of age matched healthy subjects. After 3-year antihypertensive (AHT) treatment, these hypertensives were investigated again. The aim of this study was to compare the cerebral hemodynamic changes in the regularly treated and noncompliant (untreated) hypertensives during ergometer cycling. METHODS: Nineteen of 30 previously untreated hypertensive patients could be investigated again using the same method as before. Eleven were regularly treated (treated hypertensive [T-HT] group), and 8 did not take their AHT medications due to lack of compliance (noncompliant hypertensive [NC-HT] group). Blood pressure, heart rate, end-tidal CO2 (etCO2; Capnogard capnograph), and bilateral middle cerebral artery mean blood flow velocity (MV) were continuously monitored during ergometer cycling according to the World Health Organization protocol. Values of 2-minute loading were analyzed. RESULTS: Median loading time did not differ significantly between the T-HT and NC-HT groups. After 2 minutes of cycling in treated patients, the ratio of MV and etCO changes (DeltaMV/DeltaetCO2) showed similar values as before therapy (P = .38), whereas in noncompliant patients, a further worsening of the ratio of DeltaMV/DeltaetCO2 could be observed (P = .04). CONCLUSION: The decrease of arteriolar vasodilation (ie, the ratio of DeltaMV/DeltaetCO2) could be demonstrated in the NC-HT group after 3 years. TCD combined with ergometer cycling is a useful method for evaluation of cerebral hemodynamic changes after AHT therapy.

Early-onset carotid atherosclerosis is associated with increased intima-media thickness and elevated serum levels of inflammatory markers.

BACKGROUND AND PURPOSE: Several factors have been held responsible for the development of atherosclerosis. To avoid the masking effect of age, we evaluated correlates of carotid atherosclerosis in patients <55 years of age. METHODS: Plasma lipids, oxidative resistance of low-density lipoprotein, homocysteine, inflammatory markers, plasma viscosity, and red cell deformability were measured in fasting blood samples of 100 subjects: 45 patients with >30% stenosis of the internal carotid artery, 20 patients with carotid occlusion, and 35 control subjects. Stenosis and intima-media thickness (IMT) of the carotid artery were evaluated by duplex ultrasound. RESULTS: White blood cell (WBC) count, plasma fibrinogen, C-reactive protein (CRP), and lipoprotein(a) levels were significantly higher in patients than in control subjects, and patients had increased IMT (P<0.01 for all comparisons). There was a tendency for higher homocysteine levels in patients. Smokers had higher WBC, fibrinogen, and CRP levels. After the effect of smoking was controlled for, WBC count, natural logarithmic transform of homocysteine, and online-measured IMT remained significantly higher in patients than in control subjects. WBC, fibrinogen, and CRP levels were highest in the highest IMT quartile (P=0.012, P=0.007, and P=0.036, respectively). CONCLUSIONS: Inflammatory markers and homocysteine have a more important role than lipid factors in early-onset carotid atherosclerosis. We cannot recommend the measurement of low-density lipoprotein peroxidation as a routine screening test to identify high-risk patients for early-onset carotid atherosclerosis. The confounding effect of smoking on inflammatory markers should be considered in studies on atherosclerosis.

Elevated white blood cell count, CRP and fibrinogen levels are not associated with increased anti-endothelial and anti-ox-LDL antibody, MCP-1, and RANTES levels in early onset occlusive carotid artery disease.

BACKGROUND: Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis. METHODS AND RESULTS: Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p<0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p<0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT. CONCLUSIONS: Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.

Serum asymmetric dimethylarginine negatively correlates with intima-media thickness in early-onset atherosclerosis.

BACKGROUND: Asymmetric dimethylarginine (ADMA) assumes a significant role in atherosclerosis by inhibiting the endothelial nitric oxide synthase (eNOS). Moreover, ADMA inhibits the inducible NOS (iNOS), the isoform that triggers atherosclerosis via peroxynitrite formation. Therefore, we investigated whether ADMA is a risk or protective factor in the atherosclerotic process. Intima-media thickness (IMT) of the common carotid artery, a surrogate for vascular diseases, was chosen as the outcome variable of interest. METHODS: Sixty patients younger than 55 years having at least 30% stenosis of the internal carotid artery and 30 age- and gender-matched controls were recruited at a community-based neurosonological laboratory. We investigated relatively young patients to circumvent the confounding effect age has in the development of atherosclerosis. RESULTS: The IMT showed a negative correlation with ADMA upon analysis of the pooled data (Spearman correlation coefficient -0.300, p = 0.0041) and the atherosclerotic stratum (Spearman correlation coefficient -0.323, p = 0.012). A multiple linear regression model containing all determinant factors of IMT previously identified by simple regression was used to further quantify the relationship between IMT and ADMA. The negative association between IMT and ADMA remained statistically significant (beta: -0.510, CI: -0.894, -0.127; p = 0.010), furthermore it was even stronger in the atherosclerotic stratum (beta: -0.67, CI: -1.16, -0.18; p = 0.008). CONCLUSIONS: A minimal increase in ADMA concentration may be protective by inhibiting iNOS but not eNOS in states where iNOS is induced, e.g. inflammation accompanying atherosclerosis.

Serum cholesterols have a more important role than triglycerides in determining intima-media thickness of the common carotid artery in subjects younger than 55 years of age.

OBJECTIVE: The role of serum cholesterol and triglycerides in carotid artery atherosclerosis is controversial. We measured carotid artery intima-media thickness (IMT), a marker of atherosclerosis in subjects younger than 55 years of age with a 6-fold range of serum cholesterol levels (3.93-25.03 mmol/L) and a 200-fold range of triglyceride levels (0.36-75.97 mmol/L). METHODS: Eighty-six patients with increased serum lipid values and 30 subjects with normal lipid values were included. Serum lipids were measured after an overnight fast. High-resolution sonographic investigations of the carotid arteries of all patients were videotaped. Intima-media thickness was measured offline at 1-mm increments in the distal 10-mm segments of both common carotid arteries by a reader blinded to patient characteristics. First, IMT was compared among groups defined by their cholesterol and triglyceride levels with the use of traditional cutoff values. Next, all subjects were pooled, and general regression analysis was performed to identify significant predictors of IMT with age, body mass index, lipid values, sex, diabetes, hypertension, and smoking status as independent variables. RESULTS: Intima-media thickness was larger in patient groups with high cholesterol levels (ie, the hypercholesterolemic and combined hyperlipidemic groups) than in the control, borderline, and isolated hypertriglyceridemic groups (P < .01). In the general multiple regression model, IMT correlated positively with total cholesterol level (beta = 0.343; P = .002) and age (beta = 0.3; P = .006) but not with triglyceride level. CONCLUSIONS: Both the group comparisons and the general regression analysis of the pooled data suggest that hypercholesterolemia has an important role in early onset IMT changes in the common carotid artery, whereas hypertriglyceridemia does not have an appreciable role.