Leptin, but not adiponectin, predicts stroke in males

OBJECTIVE: To test whether leptin and adiponectin are risk markers for a first-ever stroke. RESEARCH DESIGN, METHODS AND SUBJECTS: A nested case-referent study identified 276 cases with first-ever stroke (234 cases with ischaemic and 42 with haemorrhagic stroke). Prior to the stroke, they had participated in population-based health surveys in northern Sweden (median time between survey and stroke was 4.9 years). Referents were matched for sex, age, date and type of health survey, and geographical region. Putative risk markers for first-ever stroke, including blood pressure (BP), diabetes, smoking, body mass index (BMI), cholesterol, leptin, and adiponectin, were analysed by conditional logistic regression analysis. RESULTS: Increased BMI, high cholesterol and fasting glucose levels, diabetes mellitus and hypertension were found in future stroke patients. Whereas leptin levels were higher in male subjects (P = 0.004), adiponectin did not differ between groups. A high leptin level independently predicted stroke in men (OR = 2.46; 95% CI 1.08-5.62) but not in women. Adiponectin levels did not predict stroke. Males with high leptin levels developed stroke faster than males with low leptin levels (P = 0.0009), independently of traditional risk factors. CONCLUSIONS: Leptin may be an important link to the development of cerebrovascular disease in men, whereas adiponectin does not associate with future stroke.     

Genetic polymorphisms in the renin-angiotensin system confer increased risk of stroke independently of blood pressure: a nested case-control study

OBJECTIVE: The renin-angiotensin system has a pathophysiological role in cardiovascular disease through a variety of processes. Polymorphisms in involved genes have been described and implicated in stroke. The aim of this study was to investigate two polymorphisms in two genes in the renin-angiotensin system and the risk of stroke. DESIGN: A nested case-control study using baseline data obtained from population-based surveys in northern Sweden was performed. There were 275 individuals without major concomitant disease who suffered a first ever stroke during follow-up and 549 controls matched for age, sex and domicile. METHODS: Blood samples obtained at baseline were analyzed for potential risk factors including the A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene and the functional insertion/deletion polymorphism of the angiotensin-converting enzyme gene. RESULTS: Individuals with the AA genotype of the AT1R gene were at increased risk of ischemic stroke (odds ratio = 1.60; P = 0.005) compared with those with the AC and CC genotypes. The D allele of the angiotensin-converting enzyme insertion/deletion polymorphism was associated with a higher risk of stroke (odds ratio = 1.58; P = 0.014). CONCLUSION: In this prospective study, there was an association between A1166C polymorphism in the angiotensin II receptor gene and ischemic stroke. We also replicated previous observations that the D allele of the angiotensin-converting enzyme insertion/deletion polymorphism was associated with increased risk of stroke. The observed elevated stroke risks conferred by these two polymorphisms are independent of each other and common risk factors such as blood pressure, diabetes, smoking and high cholesterol levels.     

Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma

Background and Objectives Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a‐_desArg after transfusion of autologous plasma with high content of C3a‐_desArg. Material and Methods Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a‐_desArg, C3d,g, iC3), and soluble terminal complement complex (sC5b‐9) were investigated. C3a‐_desArg kinetics was investigated in regular apheresis donors. Results Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a‐_desArg, C3d,g and sC5b‐9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a‐_desArg ‐levels were above the reference value in 88% of all components. After re‐infusion of autologous plasma with high C3a‐_desArg content, there were rapid a₁ and a₂‐distribution followed by a slower b‐elimination phase. Conclusion Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a‐_desArg present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.     

Increase in Skin Autofluorescence and Release of Heart‐Type Fatty Acid Binding Protein in Plasma Predicts Mortality of Hemodialysis Patients

Advanced glycation end‐products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1‐year increase in skin autofluorescence (ΔAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty‐nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM‐1), C‐reactive protein (hs‐CRP), heart‐type fatty acid binding protein (H‐FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1‐year ΔAF of HD patients was 0.16 ± 0.06, which was around seven‐ to ninefold higher than 1‐year ΔAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1‐year ΔAF, hs‐CRP, ICAM‐1, and H‐FABP were independent predictors of overall mortality. Hypertension, 1‐year ΔAF, hs‐CRP, and H‐FABP were also independent predictors of cardiovascular mortality. One‐year ΔAF and plasma H‐FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.     

Sources of Mortality on Dialysis with an Emphasis on Microemboli

Patients on chronic hemodialysis have a shortened survival compared to the general population. There are multiple sources of morbidity and mortality unique to the dialysis population that account for this. Reasons include the effects of blood membrane interactions, intradialytic hypotension, myocardial stunning, excessive interdialytic weight gain, high‐flow arteriovenous fistulae, and impaired lipid break down by anticoagulation administered during HD. Another risk factor, not well appreciated, is the occurrence of microemboli of air (microbubbles) during HD. Such microemboli are not effectively removed by the venous air trap and the safety system provides no warning when these small microbubbles enter the venous bloodline of the extra corporeal circuit and then the venous circulation of the patient. Data indicate that the gas emboli are not fully adsorbed and become embedded by fibrin resulting in a combined clot that causes microemboli in the lung. In addition, these microbubbles (of the size of blood corpuscles) can pass the pulmonary circulation into the left heart and then into the general arterial circulation explaining their detection not only in the lungs but also in the brain and heart of patients. Risk factors for such microbubble appearance include the high blood pump speed associated with high‐efficiency dialyses. This review will discuss these various issues in relation to the better outcome of patients in Japan and also how to reduce some of these risk factors.     

In face of the increasing efficacy of lipid-lowering therapy, is there still a place for LDL-apheresis?

Based on a large body of evidence, high LDL-cholesterol concentrations in blood is a key factor of coronary heart disease (CHD). Overall, the observational studies show a curvilinear relationship between blood cholesterol level and coronary heart disease risk. Even more relevant are the randomised trials, firmly establishing that within just a few years a cholesterol-lowering therapy confers a dramatic effect on cardiovascular morbidity and mortality. More recent studies indicate that there is a greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels--i.e. lower is better. While this favours aggressive therapy, it is nevertheless imperative to precise patients selection for every therapy that entails a major commitment for the patient and medical community. Therefore, well-defined criteria for use of LDL-apheresis have yet to be established in the light of the expanding therapeutic armamentarium. Based on the current knowledge of the impact of statin therapy and anticipating that new options will further optimize the management of dyslipidemia in high-risk patients, we propose a reliable assessment of the effects of LDL-apheresis.