Beta 2 microglobulin and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events. METHODS: One thousand five of 1286 consecutive, neurologically asymptomatic patients with carotid atherosclerosis were followed for a median of 3 years (interquartile range, 2.5 to 3.5) for the occurrence of major adverse cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: We recorded 359 major cardiovascular events in 271 (27%) patients. B2M was significantly associated with the occurrence of major adverse cardiovascular events. With increasing quartiles of B2M, the adjusted hazard ratios were 1.19 (95% CI, 0.81 to 1.73), 1.51 (95% CI, 1.05 to 2.18), and 1.88 (95% CI, 1.26 to 2.79) compared with the lowest quartile, respectively (P<0.001). Adjusted hazard ratios for the occurrence of death, myocardial infarction, and stroke for increasing quartiles of B2M were 1.25 (95% CI, 0.92 to 1.70), 1.52 (95% CI, 1.12 to 2.06), and 1.62 (95% CI, 1.16 to 2.67) compared with the lowest quartile, respectively (P<0.001). Through statistical estimation of improvement in risk stratification, addition of B2M to baseline risk factors improved the risk stratification for major cardiovascular events, at least as much as high-sensitivity C-reactive protein or even better. CONCLUSIONS: B2M was independently and significantly associated with adverse cardiovascular outcome in patients with prevalent asymptomatic carotid atherosclerosis.

Cystatin C and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Renal dysfunction is a risk factor for cardiovascular events in patients with atherosclerosis. Unlike serum creatinine or estimated glomerular filtration rate, cystatin C reflects renal dysfunction independent of factors such as sex, weight, and race. We investigated whether baseline serum levels of cystatin C predict major cardiovascular events in patients with asymptomatic carotid atherosclerosis and compared the predictive value of cystatin C to these established markers of renal function. METHODS: We prospectively studied 1004 of 1286 consecutive patients with carotid ultrasound scanning. Patients were followed for the occurrence of major cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: During a median of 3 years of follow-up, we recorded 346 major cardiovascular events in 311 patients. The risk for a first major cardiovascular event increased significantly with increasing quintiles of cystatin C; hazard ratios ranged from 1.18 to 1.94 for the highest versus the lowest quintile (P<0.001 for trend). Creatinine levels showed no significant association with major cardiovascular events, and for glomerular filtration rate, only the lowest quintile was moderately associated with adverse cardiovascular outcome. CONCLUSIONS: Cystatin C was significantly and gradually associated with future cardiovascular events in patients with carotid atherosclerosis. In contrast, neither serum creatinine nor estimated glomerular filtration rate were significant predictors of adverse cardiovascular outcomes.

Immunoglobulin e-mediated allergies in lung-transplanted adults.

BACKGROUND: Immunoglobulin E (IgE)-mediated allergy has repeatedly been reported after solid organ transplantation, apparently affecting approximately 10% of pediatric organ transplant recipients. Interestingly, type 1 allergy has not been described in transplanted adults, suggesting a particular propensity in childhood. METHODS: The present cross-sectional study assessed the prevalence of type 1 allergy in 42 adult lung transplant recipients aged 25 to 50 years. Instruments included standardized interviews, skin prick tests, and serum IgE measurements. RESULTS: Ten of 42 patients (23.8%) displayed elevated specific IgE levels or positive skin prick test results against one or more allergens. Five individuals (11.9%) additionally reported corresponding clinical symptoms of type 1 allergy. No statistically significant association of sensitization or allergy prevalence with patient age, kind of immunosuppressive therapy, and time since transplantation was found. CONCLUSIONS: The phenomenon of transplantation-associated allergy is not age-restricted and thus should be assessed more thoroughly in all age groups.

[Medical clearance for missions abroad (EEU): definitions, recommendations for use and performance]. / Entsendungseignungsuntersuchung (EEU): Definition, Empfehlungen zum Untersuchungsaufwand und Einsatz.

Standards for medical clearance for private or business missions abroad are--at least in the German speaking countries--not clearly defined and mostly derived from the old terminus "Tropentauglichkeit" which means fit for mission in the tropics. The authors now define a new standard, called "Entsendungstauglichkeitsuntersuchung" which means clearance of fitness for all types of missions abroad, independent of distinct climatic zones. To meet the inhomogenous requirements of different institutions and different types of missions the medical examination proposed follows a modular structure to optimize economic and medical use of resources. Moreover, as Austria, Germany and Switzerland have different legal and economic postulates, the medical examination has to be adapted to the different premises. The definition and description of this special type of "medical clearance for missions abroad" is supplemented by recommendations for definitions of clients who should undergo such an investigation and the professionals who should perform this type of investigation. Additionally, results of this type of medical clearance are defined and prophylactic aspects in terms of pre-travel advice are mentioned.

Inflammation and Carotid Artery--Risk for Atherosclerosis Study (ICARAS).

BACKGROUND: Compelling evidence suggests that inflammation is fundamentally involved in the pathogenesis of atherosclerosis; however, temporal correlation between inflammation and morphological features of atherosclerosis progression has not been demonstrated unequivocally. METHODS AND RESULTS: We prospectively studied 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of a median of 7.5 months (range 6 to 9 months), with measurement of carotid flow velocities and categorization of carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA) were measured at baseline and follow-up. Progression of carotid atherosclerosis was found in 103 (8.1%) of 1268 patients. Hs-CRP and SAA, respectively, at baseline (P=0.004 and P=0.014) and follow-up (P<0.001 and P<0.001) and the change from baseline to follow-up (P<0.001 and P<0.001) were significantly associated with progressive atherosclerosis. Adjusted ORs (95% CI) for atherosclerosis progression with increasing quintiles of baseline hs-CRP were 1.65 (0.71 to 3.84), 1.87 (0.8 to 4.37), 3.32 (1.49 to 7.39), and 3.65 (1.65 to 8.08), and with increasing quintiles of baseline SAA, they were 0.86 (0.38 to 1.92), 0.99 (0.49 to 1.99), 1.72 (0.91 to 3.28), and 2.28 (1.24 to 4.20), respectively, compared with the lowest quintiles. CONCLUSIONS: These findings supply evidence for a close temporal correlation between inflammation and morphological features of rapidly progressive carotid atherosclerosis, which suggests that elevation or increase of the inflammatory biomarkers hs-CRP and SAA identifies the presence of active atherosclerotic disease.

Anti-beta2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant.

The presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of our study to investigate whether increased anti-beta2-GPI-antibodies predict pregnancy loss in women positive for LA. We performed a cross-sectional study in a cohort of 39 women with persistent LA, who had in total 111 pregnancies. Fifteen women had exclusively normal pregnancies (30 pregnancies) and 24 women had pregnancy losses (81 pregnancies). Anti-beta2-GPI-antibodies were determined using a semiquantitative enzyme linked immunoassay (QUANTA Lite beta2 GPI IgG and IgM; Inova Diagnostics). Increased levels of anti-beta2-GPI antibodies were significantly associated with pregnancy loss [odds ratio (OR) 9.6, 95% confidence interval (CI) 1.6-56.4]. This risk was even higher in the subgroup of women (n = 16) with more than two miscarriages or fetal loss after the first trimester [OR 13.1, 95% CI 1.4-126.3]. There was no significant association between anticardiolipin antibodies and pregnancy loss [OR 3.5, 95% CI 0.7-17.6]. The co-existence of anti-beta2-GPI and anticardiolipin antibodies was also predictive for pregnancy loss [OR 6.1, 95% CI 1.3-29.7]. Interestingly, the prevalence of thrombosis was similar between women with normal pregnancy (87%) and those with pregnancy loss (75%). We conclude that increased levels of anti-beta2-GPI antibodies are predictive for pregnancy loss among women positive for LA, and that prophylactic treatment should be considered in these women even without a history of previous pregnancy loss.

Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis.

BACKGROUND: C-reactive protein (CRP) and glycohemoglobin (HbA1c) are established risk factors for the development of cardiovascular disease. We investigated the joint effects of these parameters on cardiovascular outcome of patients with advanced atherosclerosis. METHODS AND RESULTS: We studied 454 patients with advanced atherosclerosis (median age, 69 years; 264 male). Cardiovascular risk profile, high-sensitivity CRP (hs-CRP), and HbA1c were obtained at baseline, and patients were followed for a median of 21 months (interquartile range, 13 to 26) for the occurrence of major adverse cardiovascular events (MACE) (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 166 MACE in 128 patients (28%). Cumulative event-free survival rates at 6, 12, and 24 months were 91%, 85%, and 73%, respectively. Adjusted hazard ratios for the occurrence of MACE according to increasing quartiles of hs-CRP and HbA1c were 1.35 (P=0.31), 1.90 (P=0.026) and 2.13 (P=0.007), and 1.40 (P=0.26), 1.81 (P=0.059), and 2.36 (P=0.023), respectively, compared with the lowest quartiles. Considering both parameters jointly, we found that patients with hs-CRP >0.44 mg/dL and HbA1c >6.2% (upper quartiles) were at highest risk for MACE, with each parameter adding to the prognostic information of the other. CONCLUSIONS: Inflammation, indicated by hs-CRP, and hyperglycemia, indicated by HbA1c, jointly contribute to the cardiovascular risk of patients with advanced atherosclerosis. Patients with both hs-CRP and HbA1c in the upper quartiles (>0.44 mg/dL and >6.2%, respectively) are at particularly high risk for poor cardiovascular outcome.

Prognostic impact of fibrinogen in carotid atherosclerosis: nonspecific indicator of inflammation or independent predictor of disease progression?

BACKGROUND: Fibrinogen is a key factor in the coagulation cascade, it exhibits proinflammatory properties, and it is suggested to play a pivotal role in atherogenesis. We investigated whether fibrinogen predicts future progression of carotid atherosclerosis, analyzing whether fibrinogen levels add to the prognostic information of other inflammatory parameters. METHODS: We prospectively studied 1268 consecutive patients without recent (12 months) symptoms from cerebrovascular disease. Patients underwent serial ultrasound investigations in 6- to 9-month intervals, categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed, or occluded. Fibrinogen levels were determined at baseline and follow-up. The risk for progressive carotid atherosclerosis according to fibrinogen levels was calculated, adjusting for traditional risk factors and other inflammatory parameters (C-reactive protein and serum amyloid A). RESULTS: Progression of carotid atherosclerosis was found in 117 of 1268 patients (9.2%) after a median of 8 months (range 6 to 18). Adjusted hazard ratios for atherosclerosis progression with increasing quartiles of baseline fibrinogen were 1.83 (P=0.037), 2.09 (P=0.008), and 2.45 (P=0.002), respectively, compared with the lowest quartile. Fibrinogen at follow-up also was associated with progressive disease (P=0.004). However, additionally adjusting for other inflammatory parameters diminished these associations to a nonsignificant level. CONCLUSIONS: Elevated fibrinogen, reflecting the level of inflammatory activity, is associated with progression of carotid atherosclerosis, as it was demonstrated previously for other inflammatory parameters. However, this association seems to be nonspecifically related to the extent of the inflammatory process in atherosclerotic disease rather than to specific properties of fibrinogen.

Fibrinogen predicts restenosis after endovascular treatment of the iliac arteries.

OBJECTIVE: Fibrinogen is an acute phase protein as well as a component of the coagulation cascade. Vascular inflammation and disturbed coagulation are suggested to cause restenosis after percutaneous transluminal angioplasty (PTA). We investigated the prognostic impact of fibrinogen on restenosis after endovascular treatment of iliac artery occlusive disease. METHODS: In a prospective cohort study 137 consecutive patients after iliac artery PTA (n = 74) and PTA plus selective stent implantation (n = 63) were included, 109 patients after lower limb angiography served as a control group. Patients were followed for 6 months with oscillography, ankle brachial index and duplex sonography for occurrence of restenosis. Fibrinogen and serum amyloid A (SAA), as a control parameter of inflammation, were obtained at baseline, 8, 24 and 48 h postintervention. RESULTS: PTA (adjusted OR 3.1, p = 0.05) and stenting (adjusted OR 13.3, p = 0.001) were independently associated with a higher postintervention increase of fibrinogen compared to angiography. Restenosis was found in 29 patients (21%). Patients with pre-intervention fibrinogen values in the third quartile (411-463 mg/dl) had a 6.2-fold increased adjusted risk for restenosis (p = 0.03), patients in the fourth quartile (> 463 mg/dl) had a 8.9-fold increased adjusted risk (p = 0.007). Pre-intervention SAA values were also significantly associated with restenosis (p < 0.0001). Postintervention fibrinogen and SAA levels showed no association with outcome. CONCLUSION: Balloon angioplasty and stenting of the iliac arteries cause an elevation of postintervention fibrinogen levels independently of angiographic factors. A higher pre-procedure fibrinogen level, presumably a marker of inflammatory activity, indicates a higher risk for restenosis.

Interleukin-1 cluster combined genotype and restenosis after balloon angioplasty.

The interleukin-1 system is fundamentally involved in the pathogenesis of restenosis after percutaneous transluminal angioplasty (PTA). In order to further define the clinical impact of genetic variation in this potent proinflammatory pathway we investigated the joint effects of two single nucleotide polymorphisms in the interleukin-1 beta gene [IL-1B(-511) and IL-1B(+3954)] and a variable number tandem repeat polymorphism in intron 2 of the interleukin 1 receptor antagonist gene (IL-1RN VNTR) on postintervention inflammation and occurrence of restenosis in 183 consecutive patients who underwent successful femoropopliteal PTA. C-reactive protein (CRP) and serum amyloid A (SAA) were determined pre- and 48 hours postintervention. Patients were followed up to 12 months for the occurrence of postangioplasty restenosis (> or = 50%). When analyzed separately, none of the polymorphisms was associated either with inflammation or restenosis. However, when the IL-1B (-511) and the IL-1RN VNTR genotypes were combined, a highly significant relationship was observed: Non-carriers of the two repeat allele of the IL-1RN VNTR (IL-1RN*2) who were heterozygous and homozygous for the IL-1B (-511)T allele exhibited a gradually increased inflammatory response and a higher restenosis risk. In contrast, carriers of the IL-1RN*2 and the IL-1B (-511)T allele showed a significantly better outcome. This remarkable gene dose-dependent association emphasizes the advantage of considering combinations of genetic markers rather that isolated polymorphisms in the analysis of multifactorial vascular disease.

Renal function and long-term mortality in patients with asymptomatic carotid atherosclerosis.

Renal dysfunction is a risk factor for mortality in patients with atherosclerosis. Estimated glomerular filtration rate (eGFR), cystatin C (CysC) and beta-2-microglobulin (B2M) are measures of renal function. It remains unclear, which of these parameters is the strongest predictor of outcome in patients with atherosclerosis. All-cause and cardiovascular mortality were prospectively investigated in 1,065 consecutive patients with asymptomatic carotid atherosclerosis. During a median follow-up of 6.3 years 275 patients died (25.8%), including 182 (66.2%) from cardiovascular causes. Estimated GFR, CysC and B2M were all significantly and independently associated with mortality. Inclusion of the renal parameters CysC and B2M but not of eGFR into a model with established cardiovascular risk factors improved the C-statistics significantly (p=0.0035 and 0.036, respectively; p=0.182 for eGFR). The net reclassification improvement (NRI) was 32.4% (p<0.0001) for CysC, 29% (p<0.0001) for B2M, and 16.5% (p=0.019) for eGFR. The integrated discrimination improvement (IDI) was 0.014 (p=0.0009) for CysC and 0.011 (p=0.005) for B2M while it was not significant for eGFR. Results were consistent for various subgroups with different extent of atherosclerosis. In summary, CysC and B2M were found to be independent predictors for mortality and had superior predictive value compared to eGFR in patients with asymptomatic carotid atherosclerosis. The clinical importance of these findings has to be validated in larger studies with a community-based approach.

A J-shaped association between high-sensitivity C-reactive protein and mortality in kidney transplant recipients.

In kidney transplant recipients (KTR), C-reactive protein (CRP) has been shown to be associated with increased mortality, but data on this association within the high-sensitivity (hs) range of CRP (<5 mg/l) are lacking. We prospectively studied 710 prevalent and stable KTR over >6 years. We thawed frozen plasma and measured baseline hs-CRP using an ultrasensitive assay. Detailed clinical and demographic baseline characteristics were available for study. We stratified patients by quartile of hs-CRP within the hs range (<5 mg/l), and also included KTRs whose hs-CRP was above the hs range (>5-10 and >10 mg/l). We used multivariate proportional hazards models to test for independent associations. After careful multivariate adjustment, we found a J-shaped association between hs-CRP and mortality. Compared with KTR whose hs-CRP was in the second lowest quartile of hs-CRP (0.06-1.26 mg/l), patients in the lowest quartile (<0.06 mg/l) had more than twice their mortality risk (HR = 2.07; 95% CI: 1.05-4.07), as did patients whose hs-CRP was > or =2.44 mg/l (all HRs >2.27). No association was found between hs-CRP and death-censored allograft loss. In contrast to the general population, the association between hs-CRP and mortality in KTRs is not linear, but J-shaped, suggesting that KTRs with very low hs-CRP may also be at increased risk of death.

Anti-cardiolipin antibodies and overall survival in a large cohort: preliminary report.

BACKGROUND: Anti-cardiolipin antibodies have been associated with both arterial and venous thrombosis, but their overall impact on all-cause or vascular mortality is unknown. In this study, we evaluated the influence of anti-cardiolipin antibodies on all-cause and vascular mortality. METHODS: All individuals who fulfilled the inclusion criteria (completeness of data, no admission from an intensive care unit, unique identification with name and date of birth) and whose anti-cardiolipin antibodies were measured between October 2002 and February 2004 were included in this study (n = 4756; 64% female; median age, 46 years). Death/survival and cause of death were obtained from the Austrian Death Registry. The median observation period was 1.5 years, and the study comprised 7189 person-years. RESULTS: During the study period, 184 patients (3.9%) died. There were no associations between either anti-cardiolipin IgM or IgG antibodies and both vascular death and noncancer mortality as outcome variables in a Cox regression analysis adjusted for age and sex. In contrast, the risk of cancer-related mortality was increased 2.6-fold. CONCLUSIONS: Anti-cardiolipin antibodies are associated with cancer mortality, likely as an epiphenomenon of malignancy, but they are not predictive of vascular mortality or noncancer mortality. Hence, although a clear association between anti-cardiolipin antibodies and (mostly nonfatal) vascular events has been described in the literature, our data indicate that this finding is not necessarily associated with an increase in vascular mortality.

The C-reactive protein (+)1444C/T alteration modulates the inflammation and coagulation response in human endotoxemia.

BACKGROUND: C-reactive protein (CRP) plays a major role in the immune system and is an independent risk marker of cardiovascular disease. However, CRP's role in atherogenesis as innocent bystander, causative, or even protective agent, remains unresolved. The (+)1444C/T alteration in the CRP gene has been reported to determine basal CRP concentrations. We hypothesized that this alteration may also be associated with the degree of inflammatory response and coagulation activation in a well-standardized model of systemic inflammation. METHODS: We administered 2 ng/kg endotoxin [Escherichia coli bacterial lipopolysaccharide (LPS)] intravenously to stimulate inflammation in 91 healthy young Caucasian male paid volunteers (age range, 19-40 years). Participants were confined to bed rest and fasted for 8.5 h after LPS infusion. We collected blood samples before LPS infusion and at 0, 2, 6, and 24 h after LPS infusion to measure inflammation markers [interleukin 6 (IL6), tumor necrosis factor-alpha (TNFalpha)], temperature, and coagulation markers (prothrombin fragment F(1+2), D-dimer). We analyzed the CRP 3' untranslated variant with a mutagenic separated PCR assay. RESULTS: Basal concentrations of high-sensitivity CRP were approximately 40% lower in (+)1444CC alteration carriers than in T homozygous (TT) allele carriers (P = 0.04). In contrast, basal IL6 concentrations were 2-fold higher in wild-type C homozygous (CC) than in TT individuals (P = 0.01). In response to the LPS challenge, CC individuals had 4-fold higher peak TNFalpha concentrations (P <0.01), >2.5-fold higher peak IL6 concentrations (P <0.01), and increased temperature (P <0.01). Twenty-four hours after LPS challenge, prothrombin fragment F(1+2) concentrations were 75% higher and D-dimer concentrations 50% higher in CC than in TT individuals (P <0.05). CONCLUSIONS: Genetic factors regulating CRP concentrations also modulate the individual response to endotoxin-stimulated inflammation.

Immunosuppressive therapy does not prevent the occurrence of immunoglobulin E-mediated allergies in children and adolescents with organ transplants.

BACKGROUND: Allogeneic organ transplantation has become a common procedure in acute and chronic organ failure. The major limitation, rejection of the allograft by the host's immune system, can be limited by various immunosuppressive drugs that target the adaptive T-cell response. Most of these drugs are used in the treatment of allergic diseases as well, suggesting that transplant recipients under long-term immunosuppressive therapy should not develop any sensitizations or at least not show any clinical signs of allergy. Surprisingly, organ-transplanted children and adults do report symptoms of type 1 allergies, such as allergic rhinoconjunctivitis, bronchial asthma, and food allergies. Thus far, mainly case reports and series on the occurrence of allergy after orthotopic liver transplantation exist. OBJECTIVE: Our purpose with this study was to evaluate in a cross-sectional design the prevalence of immunoglobulin E-mediated sensitizations and type 1 allergies in solid organ-transplanted children and adolescents and to identify risk factors. METHODS: Seventy-eight organ-transplanted subjects (50 kidney, 9 lung, 19 liver; mean age: 14.06 +/- 5.94 years; range 1.42 to 24.25 years) were studied by standardized interviews (modified International Study of Asthma and Allergies in Childhood [ISAAC] criteria), skin-prick tests, and measurement of specific and total serum immunoglobulin E. RESULTS: Nineteen patients (24.4%) were found to be sensitized to > or = 1 common inhalant or food allergens, as reflected by elevated specific immunoglobulin E levels and/or positive skin-prick test results, and 8 subjects (10.3%) additionally reported a corresponding present history of atopic diseases. No severe anaphylactic reactions were reported. No statistically significant associations with gender, kind of transplanted organ, distinct immunosuppressive therapies, and age at time of transplantation or age at investigation were found (chi2 test, Fisher's exact test, and Wilcoxon rank-sum test, respectively). Multiple logistic-regression analysis did not identify any independent risk factor either. CONCLUSION: This study demonstrates that therapeutic immunosuppression does not control sensitizations and clinical manifestation of type 1 allergies in organ-transplanted children and adolescents.

Cerebrospinal fluid neurone-specific enolase in mitochondrial encephalomyopathies.

Whether cerebrospinal fluid (CSF) neurone-specific enolase (NSE) contributes to the diagnosis of mitochondrial encephalomyopathies (MEMs) is unknown. Aim of the present study was thus to assess the validity of CSF-NSE in the diagnosis of MEM. CSF-NSE was determined in 24 controls, aged 28-88 years; and 23 MEM patients, aged 47-81 years. In controls, CSF-NSE was independent of sex (p = 0.849) and age (p = 0.346). Twenty-one MEM patients had clinical CNS involvement and two CNS abnormalities on imaging investigations exclusively. CSF cells were increased in 7, CSF protein in 17, CSF glucose in 1, and CSF lactate in 2 MEM patients. The upper reference limit of CSF-NSE was 14.66 ng/mL. CSF-NSE was elevated in 6 (26%) MEM patients. CSF-NSE was increased in a single MEM patient with subclinical CNS involvement. This study shows that CSF-NSE is elevated in only one quarter of the MEM patients. Determination of CSF-NSE appears to be of minor importance for the assessment of clinical or subclinical CNS involvement in MEM.

Heme oxygenase-1 genotype is a vascular anti-inflammatory factor following balloon angioplasty.

PURPOSE: To investigate the association of the heme oxygenase-1 (HO-1) genotype, which has potent anti-inflammatory capability, and the inflammatory response induced by balloon angioplasty. METHODS: Three hundred seventeen patients (188 men; median age 70 years, range 57-77) undergoing femoropopliteal balloon angioplasty (n=150) or stenting (n=61) were evaluated for upregulation of the HO-1 genotype; 106 patients undergoing lower limb angiography served as controls. The acute phase reactants C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen were measured 24 and 48 hours postintervention and compared to baseline values. An association of the relative increase (Delta, %) of these inflammatory markers with short (<25) (GT)(n) dinucleotide repeats in the HO-1 gene promoter was assessed. RESULTS: The HO-1 genotype was significantly associated with Delta CRP(24) (p<0.0001), Delta CRP(48) (p<0.0001), Delta SAA(24) (p=0.02), and Delta SAA(48) (p=0.006) after balloon angioplasty; Delta fibrinogen showed no association. Patients with a higher Delta CRP(48) after balloon angioplasty exhibited significantly reduced odds for the presence of short (<25) (GT)(n) repeats. The adjusted odds reduction in the multivariate model was 80% (p=0.002) in the third quartile of Delta CRP(48) values and 90% (p=0.001) in the fourth quartile. No association of HO-1 genotype and inflammatory response was found 24 and 48 hours after stenting (p=0.3, p=0.5) or angiography (p=0.2, p=0.6). CONCLUSIONS: The HO-1 promoter genotype is independently associated with the inflammatory response seen after balloon angioplasty. Short alleles (<25 GT repeats) seem to be an intrinsic vascular anti-inflammatory factor.

Vascular inflammation and percutaneous transluminal angioplasty of the femoropopliteal artery: association with restenosis.

PURPOSE: To determine the association of pre- and postprocedural serum levels of C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen at 6-month evaluation of restenosis after percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery. MATERIALS AND METHODS: In a prospective cohort study, 172 consecutive patients with peripheral artery disease of Fontaine stage IIa, IIb, or III who underwent successful PTA of the superficial femoral and popliteal arteries were included. Patency at 6 months was evaluated by using oscillography, ankle-brachial index, and color-coded duplex ultrasonography. The association of restenosis and CRP, SAA, and fibrinogen levels at baseline, 24 hours, and 48 hours after intervention was assessed by means of multivariate analysis with adjustment for known risk factors for restenosis. RESULTS: Restenosis was found in 56 patients (33%) within 6 months. CRP values at baseline (adjusted odds ratio, 2.2; 95% CI: 1.1, 4.2) and 48 hours after intervention (adjusted odds ratio, 2.3; 95% CI: 1.6, 3.1) were independently associated with 6-month restenosis. SAA and fibrinogen values at any time interval were not significantly associated with patency in the multivariate models. CONCLUSION: The extent of vascular inflammation as measured by means of acute-phase reactants before and after PTA of the femoropopliteal artery is associated with 6-month restenosis. Baseline and 48-hour CRP levels were independent predictors of postangioplasty outcome.

Inflammatory response to stent implantation: differences in femoropopliteal, iliac, and carotid arteries.

PURPOSE: To investigate the postintervention course of serum acute-phase reactants after stent implantation in the femoropopliteal, iliac, and carotid arteries. MATERIALS AND METHODS: This prospective cohort study included 274 consecutive patients who underwent stent implantation in the femoropopliteal (n = 95), iliac (n = 70), and carotid (n = 109) arteries. C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen levels were measured at baseline and at 48 hours after intervention. Polynomial logistic regression analysis was applied to assess the independent association of the course of acute-phase reactants and the site of stent implantation. RESULTS: Stent implantation in the femoropopliteal artery was associated with a higher postintervention increase in CRP (P =.01), SAA (P =.04), and fibrinogen (P =.01) values compared with values with iliac artery stent implantation, with adjustment for age, sex, fluoroscopy duration, contrast agent dose, complication occurrence, stenosis grade, total vessel occlusion, and stent cumulative length. No significant difference in the postintervention course of CRP (P =.9) and SAA (P =.1) levels was determined for stents implanted in the carotid artery compared with those implanted in the iliac artery; however, a higher increase in fibrinogen levels (P =.04) was noted. CONCLUSION: Stent implantation in the muscular femoropopliteal artery was associated with a more extensive vascular inflammatory response than was stent implantation in the elastic iliac and carotid arteries, independent of lesion morphology and interventional factors.

Balloon angioplasty and stent implantation induce a vascular inflammatory reaction.

PURPOSE: To investigate whether peripheral balloon angioplasty with and without stent implantation independently causes an inflammatory vascular response measured by serum acute-phase reactants. METHODS: This was a prospective cohort study enrolled 388 consecutive patients (218 men; median age 70 years, interquartile range 59-76) with peripheral artery disease undergoing balloon angioplasty (n = 187), stent implantation (n = 140), and diagnostic angiography (control group, n = 61). C-reactive protein (CRP) measured by standard and high-sensitivity assays, serum amyloid A (SAA), fibrinogen, and white blood cell (WBC) count were obtained at baseline and at 8, 24, and 48 hours postintervention. Polynomial logistic regression analysis was used to assess the independent association of acute-phase reactants and the interventional group. RESULTS: CRP levels measured by both standard and the high-sensitivity assays significantly increased after balloon angioplasty (standard CRP, p = 0.02; high-sensitivity CRP, p = 0.02) and stent implantation (standard CRP, p = 0.004; high-sensitivity CRP, p = 0.008) compared to the control group adjusting for age, sex, duration of fluoroscopy, volume of contrast, and periprocedural complications. SAA values differed only between the stent group and controls (p = 0.05). Fibrinogen and WBCs were not different among the 3 interventional groups. CONCLUSIONS: Balloon injury and stent implantation induce a vascular inflammatory response at the dilated vessel segment measurable by serum acute-phase parameters. The standard CRP assay is adequate to quantify acute-phase response in these patients.