ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans

Summary.  Background:  High-density lipoprotein (HDL) exerts a variety of anti-atherothrombotic functions, including a potent anti-inflammatory impact. In line, the direct pro-inflammatory effects of C-reactive protein (CRP) can be attenuated by HDL in vitro . Objective:  To evaluate whether this also holds true in humans, we assessed the ability of reconstituted HDL to neutralize CRP-mediated activation of coagulation and inflammation. Methods:  Fifteen healthy male volunteers received an infusion of recombinant human (rh)CRP (1.25 mg kg⁻¹ body weight). In eight of these volunteers, an infusion of human apoAI reconstituted with phosphatidylcholine (apoAI-PC; 80 mg kg⁻¹ body weight) preceded rhCRP infusion. Results:  Infusion of rhCRP alone elicited an inflammatory response and thrombin generation. In individuals who received apoAI-PC prior to rhCRP, these effects were abolished. Parallel tests in primary human endothelial cells showed that apoAI-PC preincubation with rhCRP abolished the CRP-mediated activation of inflammation as assessed by IL-6 release. Although we were able to show that rhCRP co-eluted with HDL after size-exclusion chromatography, plasmon surface resonance indicated the absence of a direct interaction between HDL and CRP. Conclusion:  Infusion of apoAI-PC prior to rhCRP in humans completely prevents the direct atherothrombotic effects of rhCRP. These findings imply that administration of apoAI-PC may offer benefit in patients with increased CRP.     

Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes

They‐They TP, Nadifi S, Rafai MA, Battas O, Slassi I. Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes.
Acta Neurol Scand: 2011: 123: 105–110.
© 2010 John Wiley & Sons A/S. Background – The role for the methylenetetrahydrofolate reductase C677T gene variants in the risk of ischemic stroke is controversial. Method – This first case–control study including 91 cases affected by ischemic stroke and 182 controls matched for age, sex, and same area was conducted in Casablanca, Morocco. Allele and genotype frequency were characterized by using PCR followed by HinfI enzymatic digestion. Results – We found no statistic association of T allele carriers genetic factors with stroke; odds ratio, 1.1; 95% confidence interval (CI), 0.59–2.04, P = 0.303. The results shown significant association of T allele carriers genetic factors with atherothrombotic subtype stroke (n = 42); odds ratio, 2.1; 95% CI: 1.17–3.8; P = 0.012, and adjusted odds ratio of 6.5; 95% CI: 1.86–23.1, P = 0.003, for TT genotype variant compared with CC wild genotype. Conclusion – We suggested that MTHFR C677T variant may be a determinant of atherothrombotic event of ischemic stroke in Morocco.     

Ethnic differences in cardiovascular risk factors in healthy Caucasian and South Asian individuals with the metabolic syndrome

BACKGROUND: The metabolic syndrome is a cluster of atherothrombotic risk factors that are commonly associated with insulin resistance. OBJECTIVES: The aim of this study was to investigate ethnic differences in insulin resistance and non-traditional cardiovascular risk factors in relation to the International Diabetes Federation (IDF) definition of the metabolic syndrome. PATIENTS AND METHODS: A total of 245 healthy South Asians and 245 age- and sex-matched Caucasians were studied. C-reactive protein (CRP), complement C3, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated from fasting plasma glucose and insulin levels. RESULTS: Fifty Caucasian (20%) and 95 (39%) South Asian subjects had the metabolic syndrome as defined by the IDF. In South Asian subjects, HOMA-IR, CRP, C3, PAI-1 and t-PA were significantly higher in subjects with the metabolic syndrome. In contrast, in Caucasian individuals there was no difference in HOMA-IR or C3 levels and only CRP, PAI-1 and t-PA were higher in subjects with the metabolic syndrome. In a logistic regression model, plasma levels of CRP and PAI-1 were independent predictors of the metabolic syndrome in Caucasians, whereas plasma levels of C3 and t-PA as well as HOMA-IR were independent predictors of the metabolic syndrome in South Asian subjects. CONCLUSIONS: In the cohort of individuals studied, the IDF definition of the metabolic syndrome was associated with insulin resistance in the South Asian but not the Caucasian population. This work also showed ethnic differences in non-traditional cardiovascular risk factors in the presence of the metabolic syndrome.     

Mechanisms of action of statins in stroke

Statins decrease the incidence of cardiovascular events and death in patients with coronary artery disease. Moreover, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study has recently demonstrated that high-dose atorvastatin may also reduce the recurrence of stroke in patients with previous stroke or transitory ischemic attack.     

Thrombogenic and Fibrinolytic Factors and Cardiovascular Risk in Non-insulin-dependent Diabetes Mellitus

Disturbances of the haemostatic system may favour the development of vascular damage and the final occlusion events in the progress of coronary heart disease (CHD). It has been shown recently in epidemiological studies, that increased concentration of several factors, mainly fibrinogen, factor VII, von Willebrand factor (vWF), and the fibrinolytic variables plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA), can be considered as risk factors for CHD. As morbidity and mortality through coronary atherosclerosis are higher in type 2 diabetic patients than in non-diabetic subjects and as insulin resistance represents a situation which favours the development of atherothrombosis, evaluation of the haemostatic factors which are recognized as risk factors may be interesting to consider in these situations. In fact, it has been shown that the fibrinolytic parameters PAI-1 and t-PA antigen are strongly related to the metabolic disorder of insulin resistance, whereas the link with fibrinogen, factor VII, and vWF remains weak. Many cross-sectional studies conducted in different populations have shown that PAI-1 and t-PA antigen (which represents t-PA/PAI-1 complexes) are strongly correlated with insulin, triglyceride, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio and blood pressure, and that the improvement of insulin resistance improves in parallel the metabolic abnormalities and the concentration of the fibrinolytic parameters. Attempts at explaining the elevated PAI-1 and t-PA antigen levels in the insulin resistance syndrome have involved many clinical and in vitro studies, in which the role of insulin, insulin propeptides, very-low-density lipoprotein (VLDL) triglyceride, insulin resistance per se, glucose, and adipose tissue have successively been analysed and the main results of these studies are presented in this review. Due to recent experimental data from animal models of thrombosis, a pathogenic role of decreased fibrinolytic activity or increased PAI-1 levels can be proposed and could play a role in the development of vascular disease in subjects with Type 2 diabetes or insulin resistance.     

血清超敏C-反应蛋白与动脉粥样硬化血栓形成性脑卒中的相关性研究

目的:探讨血清超敏C-反应蛋白(hsCRP)水平对动脉粥样硬化血栓形成性脑卒中发生风险的预测价值。方法:采用病例-对照研究,按照TOAST分型标准,纳入动脉粥样硬化血栓形成性脑卒中患者114例为病例组,同时随机抽取门诊体检人群中无心、脑及周围动脉粥样硬化病史者130例为对照组;记录动脉粥样硬化危险因素及影响hsCRP的潜在危险因素;酶联免疫吸附法测定血清hsCRP水平,比较两组间基线hsCRP水平,并将hsCRP水平进行分层(<3mg/mL,3～10mg/mL,>10mg/mL),多因素Logistic回归模型分析不同hsCRP水平患者发生动脉粥样硬化血栓形成性脑卒中的风险。结果:病例组血清hsCRP水平高于对照组(P=0.001),校正相关危险因素后,血清hsCRP水平仍高于对照组(P=0.021);以hsCRP水平以<3mg/mL为基准,未校正任何危险因素,不同水平的hsCRP预测发生动脉粥样硬化血栓形成性脑卒中的OR值依次为1.000、2.429、5.634(P<0.05),校正相关危险因素后,OR值依次为1.000、2.005、4.277(P<0.05)。结论:hsCRP水平越高,动脉粥样硬化血栓形成性脑卒中发生风险越高。     

ADIPOR2基因多态性与动脉粥样硬化血栓形成性脑梗死的相关性研究

目的：探讨脂联素受体2（ADIPOR2）基因多态性与血清脂联素（APN）水平、颈动脉内膜中层厚度（IMT）及动脉粥样硬化性脑梗死风险的相关性。方法采用病例对照研究,选取2009年9月至2014年9月该院收治的动脉粥样硬化血栓形成性脑梗死患者300例作为观察组,另选取同期300例体检健康者作为对照组。收集所有受试者的临床资料,行颈动脉检查并测量IMT ,检测血清APN水平,测定ADIPOR2基因rs12342多态性,比较组间ADIPOR2基因多态性,分析其与血清APN和IMT的关系。结果 AA基因型与GG基因型相比,患动脉粥样硬化血栓形成性脑梗死的概率增加,差异有统计学意义（OR＝1．903,95％ C I：1．092～2．703,P＝0．011）。与对照组相比,观察组中各基因型亚组IM T值均升高,A PN水平均降低,差异均有统计学意义（P＜0．01）。与GG基因型相比,AA、AG基因型IM T值均升高,APN水平均降低,差异有统计学意义（P＜0．01）。结论 AD‐IPOR2基因多态性可能是中国汉族人动脉粥样硬化性脑梗死发病的一个基因位点。     

Risk factor profile, management and prognosis of patients with peripheral arterial disease with or without coronary artery disease: results of the prospective German REACH registry cohort

Aims  Peripheral arterial disease (PAD) and coronary artery disease (CAD) are manifestations of the same underlying condition, atherothrombosis. We compared patients with PAD only with those having PAD and concomitant documented CAD in terms of characteristics, risk factors, treatment and prognosis. Methods and results  This is a subgroup analysis of the German cohort of the Reduction of Atherothrombosis for Continued Health (REACH) Registry. It includes 483 patients with PAD only, and 479 patients with PAD plus CAD. Patients with concomitant cerebrovascular disease were excluded. Symptomatic PAD was defined as intermittent claudication (IC), confirmed by ankle brachial index <0.9, or PAD-related intervention. Patients in the total cohort were predominantly elderly (mean age 67.3 ± 8.9 years), males (72.3%), current or previous smokers (80.18%), and had often abdominal obesity (49.6%). Atherosclerotic risk factors and comorbidities were highly prevalent. Patients with PAD + CAD compared to those with PAD only were significantly more intensively treated with regards to antihrombotic agents (97.1% vs. 88.8%), statins (80.2% vs. 51.6%), or ACE inhibitors/ARB (75.6% vs. 61.1%). After two-year follow-up, no significant differences between subgroups were noted for total mortality (4.6% vs. 5.5%), cardiovascular mortality (3.7% vs. 3.9%), non-fatal myocardial infarction (1.9% vs. 2.7%) but for non-fatal stroke (4.4% vs. 2.0%, P < 0.05). Conclusion  Peripheral arterial disease patients carry a high burden of risk factors and co-morbidities, and are at high risk of death and cardiovascular events. If documented CAD is absent, PAD patients are undertreated. Thus, in PAD patients, secondary cardiovascular prevention with stringent treatment of risk factors to the same extent as in CAD patients is mandatory, in line with current guidelines.     

Oral Temperature in Daily Life. A New Look in the Era of Microinflammation

It has been repeatedly shown that apparently healthy individuals and those with atherothrombotic risk factors harbor a low grade subclinical internal inflammation (microinflammation). This low grade acute phase response is relevant for the presence of atherothrombosis and future vascular events. Since these events are associated with a febrile response, we thought that it is relevant to clarify whether the microinflammatory response has an influence on the oral temperature. Included were 2,340 men and 1,280 women in whom the white blood cell count (WBCC) and differential, as well as the erythrocyte sedimentation rate (ESR), quantitative fibrinogen and high sensitivity C-reactive protein (hs-CRP) were determined in addition to the oral temperature in quiescent conditions. There was no association between these inflammatory biomarkers, except from a weak association with the absolute number of polymorphonuclear leukocytes. This association could be, however, related to the stress of the examination itself. Thus, it is unlikely that the microinflammatory response in daily life is associated, to a significant degree, with an enhanced oral temperature. The results are relevant for the findings of elevated oral temperature during conditions of acute ischemia/infarction where the temperature is probably related to the event itself and not to the patient's background microinflammation.O. Rogowski and I. Shapira should be considered first authors.