Arterial stiffness in acute COVID-19 and potential associations with clinical outcome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) interferes with the vascular endothelium. It is not known whether COVID-19 additionally affects arterial stiffness. METHODS: This case-control study compared brachial-ankle pulse wave (baPWV) and carotid-femoral pulse wave velocities (cfPWV) of acutely ill patients with and without COVID-19. RESULTS: Twenty-two COVID-19 patients (50% females, 77 [67-84] years) were compared with 22 age- and sex-matched controls. In COVID-19 patients, baPWV (19.9 [18.4-21.0] vs. 16.0 [14.2-20.4], P = 0.02) and cfPWV (14.3 [13.4-16.0] vs. 11.0 [9.5-14.6], P = 0.01) were higher than in the controls. In multiple regression analysis, COVID-19 was independently associated with higher cfPWV (ß = 3.164, P = 0.004) and baPWV (ß = 3.532, P = 0.003). PWV values were higher in nonsurvivors. In survivors, PWV correlated with length of hospital stay. CONCLUSION: COVID-19 appears to be related to an enhanced PWV reflecting an increase in arterial stiffness. Higher PWV might be related to an increased length of hospital stay and mortality.

Micro- and macrovascular function in patients suffering from primary adrenal insufficiency: a cross-sectional case-control study.

BACKGROUND: Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, patients suffering from primary adrenal insufficiency (AI) have an increased mortality, mainly due to cardiovascular diseases. Only little knowledge exists on the contribution of MC substitution to the cardiovascular risk. Therefore, this study investigates the impact of plasma renin concentration on parameters of micro- and macrovascular function. METHODS: 26 patients with primary AI [female = 18, age: 51 (28; 78) years; BMI: 24 (18; 40) kg/m2; disease duration: 18 (5; 36) years] were included in this cross-sectional analysis. Intima media thickness (IMT) and pulse wave velocity (PWV) were investigated to assess macrovascular remodeling and arterial stiffness. Microvascular function was estimated by post-occlusive reactive hyperemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded. Patients were grouped according to their median plasma renin concentration of previous visits (Reninhigh vs Reninlow) and were compared to a group of healthy women [age: 44 (43; 46) years; BMI: 24.2 (21.8; 27.5)]. RESULTS: PWV was significantly higher in AI patients compared to controls [9.9 (5; 18.5) vs 7.3 (6.8; 7.7) m/s; p < .01], whereas no differences in microvascular function could be found. In Reninlow time to peak perfusion was significantly longer [6.0 (3; 15) vs 3.5 (1.5; 11) s; p < .05], whereas no differences in IMT and PWV were observed between Reninhigh and Reninlow. No impact of GC dose was observed. CONCLUSIONS: Microvascular function is not impaired in patients with primary AI under adequate replacement therapy, although higher renin concentrations are associated with subclinical improvements. No relation between RAAS activity and macrovascular function is observed, while arterial stiffness might be increased in primary AI.

Chronic inflammation predicts long-term mortality in patients with Raynaud's phenomenon.

BACKGROUND: Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long-term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known. METHODS: In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD) were enrolled. At their initial presentation, laboratory tests for C-reactive protein (CRP), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality was recorded through a median follow-up period of 9.3 years. RESULTS: Baseline CRP, fibrinogen and haemoglobin concentration were associated with long-term mortality in an individual analysis of patients with incipient Raynaud's phenomenon. In a multivariable model including patients' age, nailfold capillaries and ANA, a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients' mortality risk. CONCLUSION: In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients' mortality in Raynaud's phenomenon.

Comparison between the impact of morning and evening doses of rivaroxaban on the circadian endogenous coagulation rhythm in healthy subjects.

UNLABELLED: ESSENTIALS: It is unknown whether single rivaroxaban doses should best be administered in the morning or evening. Circadian rhythm of coagulation/fibrinolysis was measured after morning or evening intake of rivaroxaban. Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations. Evening intake of rivaroxaban better matches the morning hypofibrinolysis. BACKGROUND: A circadian variation of the endogenous coagulation system exists with hypercoagulability and hypofibrinolysis and a corresponding peak of cardiovascular thromboembolic events in the morning. So far, no information is given as to whether single daily doses of the new oral anticoagulant drug rivaroxaban should best be administered in the morning or the evening. MATERIALS AND METHODS: Sixteen healthy male or female volunteers with a mean age of 26 ± 7 years were included in this randomized, controlled, analyst-blinded cross-over clinical trial. All subjects were given three morning and three evening single doses of 10 mg rivaroxaban. Circadian rhythms of prothrombin fragment 1 + 2, plasminogen activator inhibitor, and plasmin-antiplasmin complex were measured before any medication intake, as well as after morning or evening medication intake. Rivaroxaban concentrations were determined by an anti-activated factor X assay and liquid chromatography-mass spectrometry. MAIN RESULTS: Concentrations of rivaroxaban were higher 12 h after evening intake of rivaroxaban than 12 h after morning intake (53.3 ng mL(-1) [95% confidence interval 46.0-67.8] vs. 23.3 ng mL(-1) [19.4-29.1, respectively]). Rivaroxaban intake in the evening reduced morning F1+2 concentrations better at 8:00 AM than did administration on awakening (85 ± 25 nmol L(-1) vs. 106 ± 34 nmol L(-1) , CI: 9.4-32.1). In addition, this suppression effect was longer lasting after evening intake. CONCLUSIONS: Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations and better matches the morning hypofibrinolysis. These results might help to further improve the efficacy and safety of rivaroxaban treatment.

Speckle-Tracking-Based Evaluation of Vascular Strain at Different Sites of the Arterial Tree in Healthy Adults.

Purpose: Vascular ultrasound (US) allows the analysis of vascular strain by speckle-tracking. This study sought to assess the extent to which vas cular strain varies between different segments of the arterial tree. Furthermore, this study aimed to investigate the reproducibility of vascular strain determination as well as of the components that contribute to the variance of vascular strain measurements in different vascular beds. Materials and Methods: Speckle-tracking was used to determine the vascular strain of the abdominal aorta (AA), the common carotid artery (CCA), the common femoral (CFA) and the popliteal artery (PA) of healthy adults. Intra- and interday reproducibility and the components of variance of vascular strain of the respective arteries were determined. Results: A total of 589 US clips obtained in 10 healthy adults (7 males, 28.3 ±â€Š3.2 years) were analyzable. Vascular strain was 7.2 ±â€Š3.0 % in the AA, 5.7 ±â€Š2.1 % in the CCA, 2.1 ±â€Š1.1 % in the CFA and 1.9 ±â€Š1.1 % in the PA. The intraday coefficients of variation of vascular strain were 6.2 % (AA), 3.9 % (CCA), 3.3 % (CFA) and 6.1 % (PA), and the interday coefficients of variation were 5.9 % (AA), 8.4 % (CCA), 10 % (CFA) and 4.6 % (PA). The variance of vascular strain mainly depended on the investigated vessel and subject. Individual DUS clips, the day of examination and the (right/left) body side (in paired arteries) had no impact on the variance of vascular strain. Conclusion: Vascular strain substantially varies between different sites of the arterial tree. Speckle-tracking by DUS allows the reliable determination of vascular strain at different arterial sites.

Associations of nailfold capillary abnormalities and immunological markers in early Raynaud's phenomenon.

OBJECTIVES: Nailfold capillaroscopy (NC) and laboratory tests for antinuclear antibodies (ANA) are routinely used in parallel for detection of emerging connective tissue disease (CTD) in patients with Raynaud's phenomenon (RP). The aim of this study was to assess the associations between distinct nailfold capillary abnormalities and concomitant autoantibodies in patients with incipient RP without previously known CTD. METHOD: Patients with incipient RP without previously known CTD were included in this retrospective analysis. We analysed the association of particular capillary abnormalities (reduced density, avascular fields, dilations, giant capillaries, haemorrhages, tortuosity, ramifications, oedema) with ANA and ANA subsets (anti-Scl-70, anti-CENP-B, anti-U1-RNP, anti-dsDNA, anti-SSA(Ro), anti-SSB(La), anti-Sm, and anti-Jo-1 antibodies). We also developed a score that allows the estimation of each patient's individual probability for the presence of an ANA titre ≥ 1:160. RESULTS: The final analysis comprised 2971 patients. Avascular fields, giant capillaries, reduced capillary density, and capillary oedema were closely related to an ANA titre ≥ 1:160. Both giant capillaries and avascular fields were associated with anti-Scl-70 and anti-CENP-B antibodies. Only a weak association was found between giant capillaries and anti-U1-RNP antibodies. Each patient's individual probability for the presence of an ANA titre ≥ 1:160 can be represented by a sum score comprising giant capillaries, reduced density, avascular fields, ramifications, and oedema as well as patients' sex and age. CONCLUSION: In patients with incipient RP, anti-Scl-70 and anti-CENP-B antibodies are related most specifically to distinct capillary alterations. Although a sum score can represent the patient's probability for elevated ANA titres, NC cannot substitute for immunological tests in patients with incipient RP.

In vivo and protease-activated receptor-1-mediated platelet activation but not response to antiplatelet therapy predict two-year outcomes after peripheral angioplasty with stent implantation.

Data linking the response to antiplatelet therapy with clinical outcomes after angioplasty and stenting for lower extremity artery disease (LEAD) are scarce. Moreover, associations of in vivo and thrombin-inducible platelet activation with the occurrence of adverse events have not been investigated in these patients, so far. We therefore assessed clinical outcomes and on-treatment platelet reactivity by four test systems in 108 patients receiving dual antiplatelet therapy after infrainguinal angioplasty and stenting for LEAD. Further, in vivo and thrombin receptor-activating peptide (TRAP)-6-inducible glycoprotein (GP) IIb/IIIa activation and P-selectin expression were measured as sensitive parameters of platelet activation. The primary endpoint was defined as the composite of atherothrombotic events and target vessel restenosis or reocclusion. Residual platelet reactivity to adenosine diphosphate and arachidonic acid was similar between patients without and with adverse outcomes within two-year follow-up (all p>0.05). Further, the occurrence of clinical endpoints did not differ significantly between patients without and with high on-treatment residual platelet reactivity by all test systems (all p>0.05). In contrast, in vivo and TRAP-6-inducible platelet activation were significantly more pronounced in patients with subsequent adverse events (all p<0.05), and high levels of platelet activation were independent predictors of the primary endpoint (adjusted hazard ratios: 3.5 for high in vivo activated GPIIb/IIIa, 2.9 for high TRAP-6-inducible activated GPIIb/IIIa, 2.3 for high in vivo P-selectin, and 3 for high TRAP-6-inducible P-selectin; all p<0.05). In conclusion, in vivo and protease-activated receptor-1-mediated platelet activation predict two-year clinical outcomes in stable patients undergoing angioplasty and stenting for LEAD.

Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH). METHODS: Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups. RESULTS: Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7 ± 0.93 AU [arbitrary units] vs 1.29 ± 0.46 AU; p = 0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14 ± 0.04 AU vs 0.19 ± 0.04 AU; p < 0.0001). No differences were seen between the groups in baseline perfusion, time to peak during PORH and recovery time following PORH. CONCLUSIONS/INTERPRETATION: PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.

On-treatment function testing of platelets and long-term outcome of patients with peripheral arterial disease undergoing transluminal angioplasty.

OBJECTIVE: To assess the clinical importance of on-treatment function testing of platelets in patients on aspirin after catheter-based vascular interventions. MATERIALS AND METHODS: In 109 patients with symptomatic peripheral arterial disease (PAD) of the lower limbs, platelet function testing (adenosine diphosphate-, collagen- and epinephrine-induced aggregation using light transmission aggregometry) was performed before and at multiple time points up to 1 year after a percutaneous angioplasty. Using univariate mixture models and Box-Cox transformation to ensure normally distributed individual variances, we investigated if an intraindividual variability exists and if it has a consequence for clinical outcome. RESULTS: Response to aspirin as measured by platelet aggregometry varies considerably over time in most patients. However, the intraindividual variance over time was not significantly correlated either with restenosis/reocclusion after 1 year or with adverse long-term outcome (occurrence of death for cardiovascular cause, stroke or myocardial infarction in up to 8 years follow-up). CONCLUSIONS: Response to aspirin does not seem to have a role in determining long-term outcome in patients with symptomatic PAD. The fact that testing of platelet function at only one time point has reduced significance may have implications for all clinical settings in which aspirin is used for the prevention of thrombo-embolic events.

Wall shear stress in the superficial femoral artery of healthy adults and its response to postural changes and exercise.

OBJECTIVES: Alterations of wall shear stress (WSS) are considered to precede atherosclerosis. Local variations of WSS might contribute to the typical distribution of atherosclerotic lesions along the superficial femoral artery (SFA). We investigated the course of WSS and its response to postural changes and exercise along the SFA of healthy adults. METHODS: In forty-six healthy subjects, we determined flow velocities and internal vessel diameters in five predefined segments of the SFA using duplex ultrasound; measurements were done at rest, following exercise (30 toe raises) and after postural changes (supine and sitting). Peak and mean WSS were calculated from peak systolic and mean velocities, vessel diameter and whole blood viscosity. RESULTS: At rest, peak and mean WSS did not vary along the femoro-popliteal axis (p > 0.05); peak and mean WSS were lower in the sitting than in the supine position (p < 0.0001). After exercise, peak and mean WSS increased in all segments (p < 0.0001), showing the lowest increase in the distal Hunter's canal. CONCLUSION: Healthy adults do not exhibit local variations of WSS in the SFA at rest, but segmental differences in WSS occur after exercise. Whether these findings are related to the typical distribution of atherosclerotic lesions later in life requires further investigation.

Adenosine diphosphate-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel.

BACKGROUND: Until recently, there were hardly any data on the antiplatelet effect of clopidogrel in advanced age. Like other metabolic processes, the conversion of clopidogrel to its active metabolite may be impaired in older patients, leading to high on-treatment residual ADP-inducible platelet reactivity. OBJECTIVE: To investigate the age dependency of clopidogrel-mediated platelet inhibition. PATIENTS AND METHODS: This was a prospective observational study. We determined adenosine 5'-diphosphate (ADP)-inducible platelet reactivity using light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 191 patients on dual antiplatelet therapy after angioplasty and stenting for cardiovascular disease. RESULTS: ADP-inducible platelet reactivity increased linearly with age after adjustment for cardiovascular risk factors, type of intervention, medication, C-reactive protein (CRP) and renal function [using LTA 0.36% of maximal aggregation per year, 95% CI 0.08-0.64%, P = 0.013; using the VerifyNow P2Y12 assay 3.2 P2Y12 reaction units (PRU) per year, 95% CI 1.98-4.41 PRU, P < 0.001]. ADP-inducible platelet reactivity was significantly higher in patients aged 75 years or older compared with younger patients (P = 0.003 for LTA and P < 0.001 for the VerifyNow P2Y12 assay). Further, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients aged 75 years or older (P = 0.02 for LTA and P < 0.001 for the VerifyNow P2Y12 assay). CONCLUSION: ADP-inducible platelet reactivity shows a pronounced age dependency in the initial phase of antiplatelet therapy with clopidogrel. The clinical implications of these findings need to be addressed in future trials.

Renal artery stenosis predicts adverse cardiovascular and renal outcome in patients with peripheral artery disease.

BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are considered cardiovascular high-risk patients. Our aim was to investigate whether incidental renal artery stenosis (RAS) increases the risk for adverse cardiovascular and renal outcomes in these patients. MATERIALS AND METHODS: We prospectively enrolled 487 consecutive patients admitted for revascularization of symptomatic PAD and performed a renal overview angiogram categorizing RAS as absent (0-29%), moderate (30-59%) and severe (>or= 60%) respectively. Clinical follow-up was for median 15 months (IQR 12-22) for the occurrence of major adverse events [MAE: composite of death, myocardial infarction (MI), stroke, percutaneous coronary intervention, coronary bypass surgery, amputation and kidney failure]. Glomerular filtration rates (GFR) were obtained at 12 months to quantify the course of renal function. RESULTS: A severe RAS was found in 76 patients (15.6%). Overall MAE occurred in 121 patients (24.8%), the composite endpoint of MI, stroke, amputation and death occurred in 101 patients (20.7%). Patients with a severe RAS had a 1.87-fold increased adjusted risk for MAE (95% CI 1.12-3.12, P = 0.017), a 2.51-fold increased adjusted risk for occurrence of the composite endpoint of MI, stroke, amputation and death (95% CI 1.45-4.34, P = 0.001) and a 2.93-fold increased risk for death (95% CI 1.41-6.08, P = 0.004), compared to those of patients without RAS respectively. We observed a significant association between the decrease of GFR over the 12-month follow-up period and the severity of RAS by multivariable analysis (P = 0.044). CONCLUSION: Severe RAS in patients with symptomatic PAD is an independent predictor of major adverse cardiovascular events, adverse renal outcome and mortality.

Impact of international guidelines on the management of cardiovascular risk factors in diabetic patients with peripheral arterial disease.

AIM: Recent data on the management of cardiovascular risk factors in high risk patients showed that dyslipidemia is still treated in an inadequate way, especially in diabetic patients. We wanted to analyze the impact of the recommendation of the Inter-Society Consensus for the management of PAD (TASC-II) on the actual situation. METHODS: In this retrospective cohort study we analyzed total-, HDL-, LDL-cholesterol, triglycerides and blood glucose using capillary blood in diabetic patients, admitted to our outpatient department. Besides the recording of a complete medical history and vascular risk factors, an ABI-measurement and a carotid Duplex ultrasonography were performed at presentation. RESULTS: We studied 111 diabetic patients (44 female and 67 male) with a mean age (+/-SD) of 70, 3 (+/-9, 9) years; a BMI of 28, 2 (+/-4, 2) and a mean waist circumference of 103 (+/-12, 2) cm. Metabolic syndrome according to the NCEP-ATP-III criteria (2001) was shown in 86% (N.=95). 41% (N.=45) had clinically manifest vascular disease in a second and 23% (N.=26) even in a third vascular territory. Total-cholesterol was 183+/-43 mg/dL; LDL-C 94 +/-30 mg/dL; HDL-cholesterol 44 +/-12 mg/dl and triglycerides 219+/-103 mg/dL. A total of 33% (N.=37) in this high risk cohort attained the LDL-C target levels according to the TASC-II guidelines. A total of 68% (N.=76) was on a HMG-CoA-reductase-inhibitor, 61% (N.=68) had platelet aggregation inhibitors. CONCLUSIONS: We found poor adherence to international guidelines for secondary prevention in diabetic patients with PAD in this outpatient setting.

Lack of major gender-related differences in patients undergoing elective endovascular or surgical repair of abdominal aortic aneurysm.

AIM: The aim of this single center retrospective study was to determine gender-related differences in patients undergoing repair of aortic aneurysm. METHODS: A total of 296 consecutive patients with an abdominal aneurysm undergoing elective endovascular or surgical repair was included in the study. Among these, 24 (8.1%) were females and 272 (91.9%) were males. Demographic and clinical characteristics as well as laboratory values in terms of any potential gender-specific differences were compared. RESULTS: Females were significantly older at the time of repair than males. No gender-related differences were found analysing major clinical and laboratory parameters. CONCLUSIONS: The clinical and laboratory profile with which males and females present at the time of elective endovascular or surgical repair for aortic aneurysm is very similar. It does not reveal any potential gender-specific risk constellation. It eventually remains unclear why the prevalence of aortic aneurysm is higher in male than in females.

Lymphatic clearance of the human skin in patients with acute deep vein thrombosis using a novel fluorescent technique.

The purpose of this study was to investigate lymphatic clearance of the human skin in patients with acute deep thrombosis of the femoral vein. In 13 patients with deep vein thrombosis and no other cause for swelling of the limbs, lymphatic clearance of the skin at the foot was measured. Ten microliters of fluorescein isothiocyanatedextran 150,000 were injected intradermally and the fluorescent light intensity of the deposit measured 10 min and 24 hours after injection by window densitometry. In addition, intralymphatic pressure was measured by the servo-nulling system. The results were compared with a sex- and age-matched control group. Fluorescent light intensity decreased by 23.8 +/- 12.3 arbitrary units or by a factor of 1.8 +/- 0.5 in patients with DVT after 24 hours, which was significantly less than in healthy controls (33.7 +/- 8.9 arbitrary units or by factor 5.0 +/- 4.1, p < 0.013). Intralymphatic pressure was not different between the two groups. These results indicate that lymphatic clearance is significantly reduced in the acute phase of deep venous thrombosis.

Soluble CD40L in patients with morbid obesity: significant reduction after bariatric surgery.

BACKGROUND: Morbid obesity is associated with increased cardiovascular morbidity and mortality. Recent studies suggest that soluble CD40 Ligand (sCD40L) may play a pathogenetic role in atherothrombotic complications in cardiovascular disease as well as in inflammation and thrombosis. As morbid obesity is closely associated with chronic inflammation and insulin resistance (IR), it was of interest to study sCD40L in patients with morbid obesity before and after massive weight loss induced by bariatric surgery. PATIENTS AND METHODS: A total of 34 patients (mean age 40 +/- 12 years) with morbid obesity were studied before and 27.2 months after bariatric surgery. High sensitivity assays were used to measure concentrations of fasting sCD40L, monocyte-chemoattractant-protein-1 (MCP-1) and high-sensitive C-reactive protein (hsCRP). To investigate the associations of concentration changes of the parameters studied, differences between pre- and post-operative data were assessed and tested by univariate and multivariate linear regression analysis. RESULTS: After a mean weight loss of 33.1 +/- 18.4 kg, circulating sCD40L decreased significantly from (3.7 +/- 1.5) ng mL(-1) to (2.2 +/- 0.7) ng mL(-1), (P < 0.001). The decline in sCD40L after weight loss correlated significantly with the decrease in fasting insulin, 2-h insulin, HOMA insulin resistance (HOMA-IR), triglycerides, and the inflammatory biomarkers MCP-1 and hsCRP. CONCLUSIONS: We have shown a marked decrease in circulating sCD40L in association with an improvement of both insulin resistance and chronic inflammation in morbidly obese patients after bariatric surgery. As high sCD40L was shown to predict cardiovascular death and myocardial infarction in several prospective studies, the observed marked lowering of sCD40L might be of clinical relevance in morbidly obese patients.

No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease.

BACKGROUND: Although peripheral arterial occlusive disease (PAOD) is significantly associated with elevated homocysteine levels, the clinical relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is still unknown. MATERIALS AND METHODS: A total of 65 patients suffering from symptomatic PAOD with elevated homocysteine levels were randomized onto placebo or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP), interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL-8, Il-18, MCP-1, TF and TFPI. RESULTS: The mean reduction of homocysteine concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8 micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group. Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum group, but both remained unchanged in the control group. No treatment effect of lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed. CONCLUSION: Although homocysteine is associated with vascular disease risk in the general population and in particular with PAOD, marked lowering of homocysteine concentrations by folic acid and B-vitamin supplementation does not influence inflammatory responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These results provide evidence against a major effect of hyperhomocysteinaemia on vascular chronic inflammation or coagulation in patients with symptomatic peripheral arterial occlusive disease.

Carotid intima-media thickness, carotid wall shear stress and restenosis after femoro-popliteal percutaneous transluminal angioplasty (PTA).

OBJECTIVE: To determine the relationship between carotid intima-media thickness (IMT), carotid wall shear stress (WSS) and restenosis after femoro-popliteal percutaneous transluminal angioplasty (PTA). PATIENTS AND METHODS: Thirty-one subjects (18 men, 13 women, median age 69 years) treated with femoro-popliteal PTA for symptomatic peripheral arterial occlusive disease were enrolled. On admission, IMT, internal diameter and blood velocity of the common carotid artery (CCA) were assessed by high-resolution ultrasonography. Blood viscosity was measured and carotid WSS was calculated. Patients were followed up for 6 months for the occurrence of significant restenosis (>50%) as documented by duplex ultrasonography. Two patients were lost to follow-up. RESULTS: Fourteen patients (48%) developed restenosis at 6 months. IMT and WSS were not different in patients without and with restenosis (IMT: 0.90 (0.85-0.97) vs. 0.89 (0.84-0.93) mm, p = 0.51; WSS: 14.1 (11.9-19.2) vs. 15.9 (12.8-21.5) dyne/cm2, p = 0.48). The hazard ratio of incident restenosis as estimated by Cox regression analysis was 0.04 for IMT (p = 0.23; 95% CI 0.0001-8.22) and 1.07 for WSS (p = 0.10; 95% CI 0.98-1.17). CONCLUSIONS: In this pilot study involving a limited number of patients, carotid IMT and carotid WSS are not significantly related to restenosis at 6 months after femoro-popliteal PTA. This might be the result of different underlying pathophysiology for atherosclerosis and restenosis.

[Hypoplasia of the descending thoracic and abdominal aorta in Williams-Beuren syndrome]. / Hypoplasie der deszendierenden Aorta thoracalis und der Aorta abdominalis bei Williams-Beuren-Syndrom.

Hypoplasia of the descending thoracic and abdominal aorta is a very rare condition and its etiology is poorly understood. Associations with congenital and acquired disorders have been reported. In this article we present the case of a 24-year-old woman with hypoplasia of the thoracic and abdominal aorta and Williams-Beurensyndrome. This rare syndrome is attributed to deletions of genes on chromosome 7, among other the elastin-gene, and is characterized by cardiovascular anomalies, dysmorph facial features and mental retardation. The patient presented with a history of severe hypertension and recurrent abdominal pain since childhood. Diagnosis was established by duplex-sonography and magnetic resonance angiography. The patient was treated by an aortoaortic bypass from the ascending to the infrarenal aorta with reinsertion of the visceral and the right renal arteries. It is essential to recognize the condition early to withhold high morbidity and mortality resulting from long standing severe hypertension.

Acroparesthesia and acral arterial occlusions as first manifestations of essential thrombocythemia.

Thrombocytosis is either caused by a reactive process (secondary thrombocytosis) or by a clonal bone marrow disorder The latter category includes essential thrombocythemia with bleedings and thrombotic complications as major causes of illness and death in this patients. We describe a 43-year-old man with a 6 months history of acroparesthesia in his toes. Half a year after onset of these symptoms, he noticed a bluish discoloration of digit V of his left foot. On first presentation physical examination revealed a bluish discoloration of all toes and a cold and blue digit V of the left foot. Peripheral pulses were all palpable, normal ankle systolic pressure measurements and normal pulse volume recordings except for digit V of the left foot were found. Laboratory tests revealed thrombocytosis of 800000/microliter. On treatment with acetylsalicylacid, prostanoids intravenously and low molecular weight heparin, the patient became asymptomatic and pulse volume recording of digit V was normalized. After exclusion of cardial or vascular sources of embolism by utrasonography bone marrow aspirate and biopsy supported the diagnosis of essential thrombocythemia.