Biomedical subjects

Markus Exner

Publications and source records attributed to Markus Exner.

At least 37 records · Page 2Linked to original sources

PubMed2005

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.

Adult↗

PubMed2005

Microsatellite polymorphism in the heme oxygenase-1 gene promoter and cardiac allograft vasculopathy.

BACKGROUND: The heme oxygenase-1 (HO-1) isoenzyme has recently been suggested to protect transplants from ischemia-reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study, we investigated the impact of the promoter polymorphism on the development of cardiac allograft vasculopathy (CAV) in human heart transplants. METHODS: We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV. RESULTS: Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30). CONCLUSION: In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants.

Adult↗

PubMed2005

Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma.

Distinguishing renal oncocytoma from chromophobe and other renal carcinomas is essential, considering their differing biological potentials. Although renal oncocytoma is considered a benign tumor, chromophobe renal cell carcinoma has potentially malignant biological behavior. The numerous reported studies on distinguishing these 2 entities have been based on morphological, histochemical, immunohistochemical, ultrastructural, and cytogenetic features. But none of these features has proven to be reliably specific, especially in tumors with overlapping phenotypes. We report a novel immunohistochemical approach based on the expression of a recently described kidney-specific cadherin (Ksp-cadherin) for the differential diagnosis of these 2 tumors. We compared Ksp-cadherin expression in 212 renal tumors, including 102 clear cell renal carcinomas, 46 papillary renal cell carcinomas, 30 chromophobe carcinomas, 3 collecting duct carcinomas, and 31 oncocytomas. In addition, we examined the expression of epithelial membrane antigen, vimentin, CK7, and Hale's colloidal iron staining. We found that chromophobe renal cell carcinomas consistently (96.7% of cases) demonstrated a distinctive membrane pattern of Ksp-cadherin expression, whereas renal oncocytomas (3.2%), clear cell renal cell carcinomas (0%), papillary renal cell carcinomas (2.2%), and collecting duct carcinomas (0%) usually did not express Ksp-cadherin. CK7 expression was found in 90.0%, 6.5%, 7.8%, 76.1%, and 33.3% of these tumor cases, respectively. Whereas CK7 was detected in different types of renal cell carcinomas, Ksp-cadherin was expressed almost exclusively in chromophobe renal cell carcinomas. Immunohistochemical analysis of Ksp-cadherin offers a fast, reliable approach for the distinguishing between renal oncocytoma and chromophobe renal cell carcinoma that is applicable for routine pathology laboratory studies without the need for time-consuming and costly ancillary studies.

Adenocarcinoma↗

PubMed2005

Association of neutrophils and future cardiovascular events in patients with peripheral artery disease.

OBJECTIVE: We hypothesized that higher neutrophil counts are associated with an increased incidence of major adverse cardiovascular events (MACE) in patients with clinically advanced atherosclerosis. METHODS: We prospectively studied 398 patients (233 men; median age, 69 years) with symptomatic peripheral artery disease who were admitted to the inpatient ward of the angiology department of a tertiary care university hospital in a cohort study. Total and differential white blood cell (WBC) counts were obtained, and patients were followed for MACE, defined as myocardial infarction, percutaneous coronary interventions, coronary artery bypass grafting, stroke, carotid revascularization, and death. RESULTS: During a median follow-up of 20 months, 140 MACE occurred in 105 patients (26%). Multivariate Cox proportional hazards analysis was used to assess the association of differential WBC count parameters (in tertiles) with MACE and their interrelation with traditional cardiovascular risk factors and other parameters of inflammation. Patients with neutrophil counts >5.8 G/L (upper tertile) exhibited an increased adjusted risk for all MACE (hazards ratio [HR], 1.83; P = .017), death (HR, 3.39; P = .010), and the composite of myocardial infarction, stroke, and death (HR, 2.20; P = . 012) compared with patients in the lower tertile (<4.4 G/L), independently of traditional cardiovascular risk factors and levels of high-sensitivity C-reactive protein. Only neutrophils, but not eosinophils, basophils, monocytes, lymphocytes, or the total WBC count showed a significant association with cardiovascular outcome. CONCLUSION: In patients with peripheral artery disease, neutrophil counts in the upper tertile (>5.8 G/L) indicate a substantially increased risk for major adverse cardiovascular events, adding to the prognostic information of traditional atherothrombotic risk factors and other parameters of inflammation.

Aged↗

PubMed2005

Copper- and magnesium protoporphyrin complexes inhibit oxidative modification of LDL induced by hemin, transition metal ions and tyrosyl radicals.

The oxidative modification of LDL may play an important role in the early events of atherogenesis. Thus the identification of antioxidative compounds may be of therapeutic and prophylactic importance regarding cardiovascular disease. Copper-chlorophyllin (Cu-CHL), a Cu(2+)-protoporphyrin IX complex, has been reported to inhibit lipid oxidation in biological membranes and liposomes. Hemin (Fe(3+)-protoporphyrin IX) has been shown to bind to LDL thereby inducing lipid peroxidation. As Cu-CHL has a similar structure as hemin, one may assume that Cu-CHL may compete with the hemin action on LDL. Therefore, in the present study Cu-CHL and the related compound magnesium-chlorophyllin (Mg-CHL) were examined in their ability to inhibit LDL oxidation initiated by hemin and other LDL oxidizing systems. LDL oxidation by hemin in presence of H(2)O(2) was strongly inhibited by both CHLs. Both chlorophyllins were also capable of effectively inhibiting LDL oxidation initiated by transition metal ions (Cu(2+)), human umbilical vein endothelial cells (HUVEC) and tyrosyl radicals generated by myeloperoxidase (MPO) in presence of H(2)O(2) and tyrosine. Cu- and Mg-CHL showed radical scavenging ability as demonstrated by the diphenylpicrylhydracylradical (DPPH)-radical assay and estimation of phenoxyl radical generated diphenyl (dityrosine) formation. As assessed by ultracentrifugation the chlorophyllins were found to bind to LDL (and HDL) in serum. The present study shows that copper chlorophyllin (Cu-CHL) and its magnesium analog could act as potent antagonists of atherogenic LDL modification induced by various oxidative stimuli. As inhibitory effects of the CHLs were found at concentrations as low as 1 mumol/l, which can be achieved in humans, the results may be physiologically/therapeutically relevant.

Atherosclerosis↗

PubMed2005

Aluminum ions stimulate the oxidizability of low density lipoprotein by Fe2+: implication in hemodialysis mediated atherogenic LDL modification.

OBJECTIVE: Al(3+) stimulates Fe(2+) induced lipid oxidation in liposomal and cellular systems. Low-density lipoprotein (LDL) oxidation may render the particle atherogenic. As elevated levels of Al(3+) and increased lipid oxidation of LDL are found in sera of hemodialysis patients, we investigated the influence of Al(3+) on LDL oxidation. MATERIALS AND METHODS: Using different LDL modifying systems (Fe(2+), Cu(2+), free radical generating compounds, human endothelial cells, hemin/H(2)O(2) and HOCl), the influence of Al(3+) on LDL lipid and apoprotein alteration was investigated by altered electrophoretic mobility, lipid hydroperoxide-, conjugated diene- and TBARS formation. RESULTS: Al(3+) could stimulate the oxidizability of LDL by Fe(2+), but not in the other systems tested. Al(3+) and Fe(2+) were found to bind to LDL and Al(3+)could compete with Fe(2+) binding to the lipoprotein. Fluorescence polarization data indicated that Al(3+) does not affect the phospholipid compartment of LDL. CONCLUSIONS: The results indicate that increased LDL oxidation by Fe(2+) in presence of Al(3+) might be due to blockage of Fe(2+) binding sites on LDL making more free Fe(2+) available for lipid oxidation.

Aluminum↗

PubMed2005

Role of CXCR3 in cellular but not humoral renal allograft rejection.

CXCR3, a chemokine receptor mainly expressed by T cells, is involved in animal transplant models and in human allograft rejection. CXCR3 expression was localized in formalin-fixed, paraffin-embedded renal allograft biopsies without signs of rejection (C4d-negative, Banff 0, n = 16), with C4d deposits as a sign of humoral rejection (C4d-positive, Banff 0, n = 8), with cellular rejection (C4d-negative, Banff I, n = 7) and with signs of both cellular and humoral rejection (C4d-positive, Banff 1, n = 5). Small, round infiltrating cells were CXCR3-positive. A high number of these cells was present in biopsies with cellular rejection (independent of C4d deposition). CXCR3-positive cells diffusely infiltrated the interstitium, including the tubular epithelium (tubulitis). CXCR3 scores and the area of CXCR3 staining were significantly higher in cellular rejection, when compared to biopsies without rejection, and with deposition of C4d alone. CXCR3-positive cells infiltrate renal allografts during cellular rejection, whereas C4d deposition is not associated with the recruitment of these cells.

Complement C4b↗

PubMed2005

Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by organized thromboemboli that obstruct the pulmonary vascular bed. Although CTEPH is a serious complication of acute symptomatic pulmonary embolism in 4% of cases, signs, symptoms and classical risk factors for venous thromboembolism are lacking. The aim of the present study was to identify medical conditions conferring an increased risk of CTEPH. We performed a case-control-study comparing 109 consecutive CTEPH patients to 187 patients with acute pulmonary embolism that was confirmed by a high probability lung scan. Splenectomy (odds ratio=13, 95% CI 2.7-127), ventriculo-atrial (VA-) shunt for the treatment of hydrocephalus (odds ratio=13, 95% CI 2.5-129) and chronic inflammatory disorders, such as osteomyelitis and inflammatory bowel disease (IBD, odds ratio=67, 95% CI 7.9-8832) were associated with an increased risk of CTEPH.

Adult↗

PubMed2005

Interleukin-1 gene cluster variants and abdominal aortic aneurysms.

Inflammation is a key factor in the pathogenesis of abdominal aortic aneurysms (AAA). Interleukin 1 (IL-1), a fundamental regulator of the inflammatory cascade, has been shown to be involved in this process. Several functional polymorphisms in the IL-1 gene cluster are known. In this matched case-control study, we investigated a potential association between six genetic variants in IL-1 and IL-1 receptor antagonist (IL-1 RN) with AAA. We enrolled 405 individuals, 135 consecutive patients with AAA were individually age- and sex-matched to 270 patients with coronary artery disease (CAD). Traditional cardiovascular risk factors and IL-1 genotypes were determined, and the distribution of six single nucleotide polymorphisms were compared between patients and controls by multivariable conditional logistic regression analysis: IL-1A (-889) C>T, IL-1A (+4845) G>T, IL-1B (-511) C>T, IL-1B (-31) C>T, IL-1B (+3954) C>T and IL-1RN (+2018) C>T. IL-1A (-889) C>T and IL-1A (+4845) G>T (kappa 0.98,95% CI 0.96 to 1.00), and IL-1B (-511) C>T and IL-1B (-31) C>T (kappa 0.98, 95% CI 0.96 to 1.00) were closely linked, therefore IL-1A (-889) C>T and IL-1B (-31) C>T were not considered for further analyses. None of the 4 remaining polymorphisms showed a significant association with AAA: IL-1RN (+2018) C>T (p = 0.061), IL-1B (+3954) C>T (p = 0.51), IL-1B (-511) C>T (p = 0.61) and IL-1A (+4845) G>T (p = 0.81). No significant first-degree interactions between the genetic variants and AAA were detected. In conclusion,these six genetic variants in the interleukin- I gene cluster do not seem to play a clinically relevant role in the pathogenesis of AAA, although we cannot rule out the existence of higher degree gene-gene or gene-environment interactions.

Aged↗

PubMed2004

The role of heme oxygenase-1 promoter polymorphisms in human disease.

Heme oxygenase (HO) seems to be a novel protective factor with potent anti-inflammatory, anti-oxidant, and anti-proliferative effects. HO-1, the inducible isoform, is expressed in various tissues and is upregulated by multiple stimuli. However, humans differ quantitatively in their ability to mount an HO-1 response, modulated by two potentially functional polymorphisms in the HO-1 gene promoter region. From several studies it seems that the ability of a patient with certain genotypes to respond strongly in terms of upregulating HO-1 may be an important endogenous protective factor. In the present article we systematically review the hitherto published evidence that promoter polymorphisms in the HO-1 gene exert functional importance by influencing the level of HO-1 expression in different organ systems.

5' Untranslated Regions↗

PubMed2004

Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort.

BACKGROUND: Capillary deposition of the complement split product C4d has turned out to be a valuable marker of antibody-mediated rejection. The impact of pre- and posttransplant variables including particular immunosuppressive regimens on the frequency of C4d deposition has not yet been systematically investigated in a large multivariate analysis. METHODS: In this retrospective study, the authors evaluated the incidence of C4d deposition in 388 kidney transplant recipients subjected to diagnostic biopsy within the first 6 months and analyzed the influence of potential confounders on the rate of C4d-positive graft dysfunction by applying multivariate logistic regression. RESULTS: Sixty-six recipients (17%) developed linear C4d deposits in at least a quarter of peritubular capillaries, a finding associated with inferior 1-year allograft survival (73% vs. 88% in C4d-negative patients, P=0.0003). A 50% reduction in the odds of C4d-positive graft dysfunction was found if calcineurin inhibitor or mycophenolate mofetil (MMF) therapy was started 2 to 4 hr before transplantation when compared with initiation after surgery (adjusted odds ratio [OR], 0.5; P=0.03). No differences with respect to C4d staining results were found for the use of tacrolimus, MMF, or sirolimus, or for cyclosporine C2 monitoring. Retransplantation (OR, 3.6; P<0.001) and presensitization (OR, 3.1; P=0.002) turned out to be strong independent risk factors for C4d deposition. CONCLUSIONS: The authors' results suggest a reduced risk of C4d-positive graft dysfunction for patients receiving immunosuppression before transplantation. Apart from first dose timing, no influence of particular immunosuppressive strategies on C4d staining results was found.

Adult↗

PubMed2004

Thiocyanate catalyzes myeloperoxidase-initiated lipid oxidation in LDL.

There is evidence that LDL oxidation may render the lipoprotein atherogenic. The myeloperoxidase-hydrogen peroxide (MPO/H2O2) system of activated phagocytes may be involved in this process. Chloride is supposed to be the major substrate for MPO, generating reactive hypochlorous acid (HOCl), modifying LDL. The pseudo-halide thiocyanate (SCN-) has been shown to be a suitable substrate for MPO, forming reactive HOSCN/SCN*. As relatively abundant levels of SCN- are found in plasma of smokers--a well-known risk group for cardiovascular disease--the ability of SCN- to act as a catalyst of LDL atherogenic modification by MPO/H2O2 was tested. Measurement of conjugated diene and lipid hydroperoxide formation in LDL preparations exposed to MPO/H2O2 revealed that SCN- catalyzed lipid oxidation in LDL. Chloride did not diminish the effect of SCN- on lipid oxidation. Surprisingly, SCN inhibited the HOCl-mediated apoprotein modification in LDL. Nitrite--recently found to be a substrate for MPO--showed some competing properties. MPO-mediated lipid oxidation was inhibited by heme poisons (azide, cyanide) and catalase. Ascorbic acid was the most effective compound in inhibiting the SCN- -catalyzed reaction. Bilirubin showed some action, whereas tocopherol was ineffective. When LDL oxidation was performed with activated human neutrophils, which employ the MPO pathway, SCN- catalyzed the cell-mediated LDL oxidation. The MPO/H2O2/SCN- system may have the potential to play a significant role in the oxidative modification of LDL--an observation further pointing to the link between the long-recognized risk factors of atherosclerosis: elevated levels of LDL and smoking.

Antioxidants↗

PubMed2004

Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas.

BACKGROUND: The growth of most tumors depends on the formation of new blood vessels. In contrast to genetically unstable tumor cells, the endothelial cells of tumor vessels are considered to be normal diploid cells that do not acquire mutations. METHODS: Using a combined immunohistochemical and fluorescence in situ hybridization assay, we examined the endothelial cells in 27 B-cell lymphomas for cytogenetic alterations that are known to be present in the lymphoma cells. RESULTS: We found that 15 to 85 percent (median, 37 percent) of the microvascular endothelial cells in the B-cell lymphomas harbored lymphoma-specific chromosomal translocations. In addition, numerical chromosomal aberrations were shared by the lymphoma cells and the endothelial cells. CONCLUSIONS: Our findings suggest that microvascular endothelial cells in B-cell lymphomas are in part tumor-related and therefore reflect a novel aspect of tumor angiogenesis.

Adult↗

PubMed2004

Interleukin-6 promoter genotype and restenosis after femoropopliteal balloon angioplasty: initial observations.

PURPOSE: To investigate whether there is an association between a functional polymorphism in the interleukin (IL)-6 gene promoter (-174)G/C and restenosis after percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery. MATERIALS AND METHODS: A total of 281 patients underwent PTA of the femoropopliteal artery during the study period; 23 (8%) patients had to be excluded due to missing genetic data. We studied 258 patients with intermittent claudication (n = 174) or critical limb ischemia (n = 84). The IL-6 promoter genotype was determined from venous blood samples before intervention by using a mutagenically separated polymerase chain reaction, and patients were followed up for 6 months with duplex ultrasonography for the occurrence of restenosis (> or =50%) after angioplasty. Multivariate Cox proportional hazards analysis was performed to assess the association between the IL-6 promoter genotype and restenosis, with adjustment for possible confounders such as atherosclerotic risk factors and angiographic covariates. RESULTS: The 6-month restenosis rate was 26% (23 of 90) in patients with the (-174)GG genotype, 28% (33 of 117) with the (-174)GC genotype, and 43% (22 of 51) with the (-174)CC genotype (P =.044). Homozygous carriers of the (-174)C allele ([-174]CC) exhibited a 2.42-fold increased adjusted risk for restenosis (95% CI: 1.28, 4.58; P =.007) compared with homozygous (-174)G allele carriers ([-174]GG). Heterozygous carriers ([-174]GC) had no significantly increased restenosis risk (hazard ratio, 1.37; 95% CI: 0.84, 2.22; P =.21). CONCLUSION: The IL-6 promoter polymorphism (-174)G/C seems to influence the occurrence of restenosis after PTA. Homozygous carriers of the (-174)C allele have an increased rate of intermediate-term restenosis.

Aged↗

PubMed2004

Heme oxygenase-1 genotype and restenosis after balloon angioplasty: a novel vascular protective factor.

OBJECTIVES: We investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty. BACKGROUND: Heme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats. METHODS: We studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis. RESULTS: Restenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis. CONCLUSIONS: The HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty.

Aged↗

PubMed2004

Donor heme oxygenase-1 genotype is associated with renal allograft function.

BACKGROUND: The heme oxygenase (HO) isoenzyme HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study we investigated the impact of the promoter polymorphism of kidney allograft donors on clinical outcomes after transplantation. METHODS: We enrolled 101 recipients of cadaveric donor kidney allografts (who underwent transplantation between June 1998 and September 1999) in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes. RESULTS: Fifty patients (49.5%) had received a kidney from a donor with at least one class S allele. Recipients of allografts from a class S allele carrier had significantly lower 1-year serum creatinine levels (median 1.46 mg/dL, interquartile range 1.17-1.68 mg/dL) compared with recipients of a non-class S allele donor kidney (median 1.61 mg/dL, interquartile range 1.38-2.22 mg/dL, P =0.01). After adjustment for cold ischemia time, retransplantation, donor age, delayed graft function, and HLA mismatch, recipients of a class S allele transplant had serum creatinine levels 0.81 times (95% confidence interval: 0.70-0.95, P =0.01) those of recipients of a non-class S allele transplant. The two patient groups did not differ significantly with respect to the incidence of delayed graft function, allograft rejection, or immunologic graft loss. CONCLUSION: Our data suggest an influence of the HO-1 gene promoter polymorphism on kidney allograft function and thus support previous studies indicating a protective effect of HO-1 induction in organ transplantation.

Adult↗

PubMed2004

Serum creatinine predicts mortality in patients with peripheral artery disease: influence of diabetes and hypertension.

BACKGROUND: Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy. We investigated the association of renal impairment, traditional cardiovascular risk factors and all-cause mortality in patients with symptomatic peripheral artery disease (PAD). METHODS: We studied 515 patients with advanced PAD (intermittent claudication, n = 410; critical ischemia, n = 105). Cardiovascular risk profile and calculated glomerular filtration rate (GFR) were obtained at baseline and patients were followed for median 21 months (interquartile range 12 to 25) for mortality. RESULTS: Sixty-five patients (13%) died. Cumulative survival rates at 6, 12, and 24 months were 97%, 95%, and 89%, respectively. Adjusted hazard ratios for mortality according to decreasing quartiles of GFR were 1.2, 2.5, and 5.9 compared to the highest quartile (P < 0.001). The association between renal impairment and mortality was independent of diabetes and hypertension, suggesting that decreased GFR adds to the prognostic value of traditional cardiovascular risk factors. CONCLUSION: Renal impairment is associated with an increased risk for mortality in patients with advanced peripheral artery disease, irrespective of the coincidence of arterial hypertension and diabetes mellitus. This suggests that impaired renal function exerts an unfavorable effect on patient's outcome, independently of these cardiovascular and renal risk factors.

Aged↗

PubMed2004

Statin therapy improves cardiovascular outcome of patients with peripheral artery disease.

AIMS: We sought to examine the interrelationship between statin use, inflammation, and outcome of high-risk patients with advanced atherosclerosis. METHODS AND RESULTS: We prospectively studied 515 patients with severe peripheral artery disease (median age 70 years, 296 males). The cardiovascular risk profile and laboratory parameters of inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid A [SAA], fibrinogen, serum albumin, neutrophil counts) were obtained, and patients were followed for a median of 21 months (interquartile range 12-25) for the occurrence of myocardial infarction (MI) and death. We observed 19 MIs (5 fatal and 14 nonfatal) and 65 deaths. Cumulative survival and event-free survival rates (freedom from death and MI) at 6, 12, and 24 months were 97%, 95%, and 89%, and 96%, 93% and 87%, respectively. Patients receiving statin therapy (n=269, 52%) had a lower level of inflammation (hs-CRP p<0.001, SAA p=0.001, fibrinogen p=0.007, albumin p<0.001, neutrophils p=0.049) and better survival (adjusted hazard ratio [HR] 0.52, p=0.022) and event-free survival rates (adjusted HR 0.48, p=0.004) than patients not treated with statins. However, patients with low inflammatory activity (hs-CRP < or =0.42 mg/dl) had no significant benefit from statin therapy (p=0.74 for survival; p=0.83 for event-free survival), whereas in patients with high hs-CRP (>0.42 mg/dl) statin therapy was associated with a significantly reduced risk for mortality (adjusted HR 0.58, p=0.046) and the composite of myocardial infarction and death (adjusted HR 0.46, p=0.016). CONCLUSION: Statin therapy is associated with a substantially improved intermediate-term survival of patients with severe peripheral artery disease and a high inflammatory activity, whereas in patients with low hs-CRP no survival benefit was observed.

Aged↗