不同白细胞亚型在急性脑梗死患者预后中的价值

目的探讨不同白细胞亚型与急性脑梗死患者神经损伤严重程度和预后的关系。方法纳入779例出现症状后72 h内入院的首次急性脑梗死患者。调查患者入院时外周血白细胞亚型计数与初始中风严重程度和3月后功能恢复的相关性。结果总白细胞和嗜中性粒细胞计数越高,患者入院时脑中风程度越严重(P0.001);相反,淋巴细胞计数越少,3月后功能预后越差(OR=0.706,P=0.020)。结论急性脑梗死患者入院时检测嗜中性粒细胞和淋巴细胞计数对患者预后具有一定的预测价值。     

Predictive value of white blood cell subtypes for long-term outcome following myocardial infarction

IntroductionElevation of total white blood cells (WBC) count is associated with higher mortality in patients with acute coronary syndromes. However, it is unknown which specific subset of leukocytes best correlates with increased risk of adverse outcome.Methods and resultsWe prospectively studied the predictive value of WBC subtypes for long-term outcome in 1037 patients with acute myocardial infarction (AMI). Total WBC, neutrophil, monocyte and lymphocyte counts, and high-sensitivity C-reactive protein (CRP) were obtained in each patient. The median duration of follow up was 23 months (range, 6–42 months). Analyzed separately, baseline total WBC (HR 2.2, 95% CI 1.5–3.3; P < 0.0001), neutrophil (HR 2.7, 95% CI 1.8–4.1; P < 0.0001) and monocyte (HR 1.9, 95% CI 1.3–2.8; P = 0.001) counts in the upper quartile, and lymphocyte count in the lower quartile (HR 1.5, 95% CI 1.1–2.3; P = 0.03), were all independent predictors of mortality. Comparing nested models, adding other WBC data failed to improve model based on neutrophil count. In contrast, adding neutrophil count to the models based on total WBC (P = 0.01), on monocyte count (P < 0.0001) or on lymphocyte count (P < 0.0001) improved the prediction of the models. Neutrophil count in the upper quartile (≥9800 μL^?1) remained a strong independent predictor of mortality after adjustment for left ventricular systolic function and for CRP (HR 2.2, 95% CI 1.6–3.0; P < 0.0001).ConclusionOf all WBC subtypes, elevated neutrophil count best correlates with mortality in patients with AMI. Neutrophil count provides additive prognostic information when combined with CRP.     

Predictive value of admission blood glucose level on short-term mortality in acute cerebral ischemia

BackgroundAdmission hyperglycemia increases the risk of death in patients with acute stroke. However, the most appropriate cut-off of glucose level indicating an increased risk of short-term mortality remains unknown.Purpose and methodsWe aimed at establishing the optimum cut-offs of several variables (including admission blood glucose levels) predicting case-fatality (72 hours, 7 days) and unfavorable outcome [modified Rankin Scale (mRS) score 5–6 at 7 days] in consecutive first-ever acute ischemic stroke. Receiver operating characteristic (ROC) curves were constructed.ResultsEight hundred eleven consecutive patients were included [median age of 77 (69–83) years; 418 (52%) male; 239 (30%) diabetics; median admission National Institutes of Health Stroke Scale (NIHSS) 7 (4–12), 32 (4%) dead within 72 hours; 64 (8%) dead within day 7; 155 (19%) with unfavorable outcome]. Median admission glucose levels were 113 (97–155) mg/dL. Diabetics had significantly higher median glucose levels than non-diabetics [163 (133–214) vs. 107 (92–123) mg/dL, p < 0.001]. According to ROC analysis, the only significant predictive value of glycemia was ≥ 143 mg/dL for 72-hour fatality (sensitivity 88% and specificity 70%) especially in non-diabetics (sensitivity 88% and sensitivity 62%). This cut-off point was an independent predictor for 72-hour fatality (overall: OR = 4.0, CI = 1.6–9.9, p = 0.003; non-diabetics: OR = 4.9, CI = 1.7–14.5, p = 0.004). The cut-offs of fasting total cholesterol levels and admission leukocytes had poor predictive values for each outcome, while those of admission NIHSS had good discrimination in predicting short-term outcome measures.ConclusionsAdmission hyperglycemia (≥ 143 mg/dL) is a strong and an independent predictor for 72-hour fatality, especially in patients with no prior history of diabetes mellitus.     

Diabetic and non-diabetic subjects with ischemic stroke: differences, subtype distribution and outcome

Background and aimDiabetes mellitus increases the risk of stroke, and pathophysiological changes of diabetic cerebral vessels may differ in comparison with non-diabetic ones; nonetheless, the clinical and prognostic profile of stroke in diabetic patients is not yet fully understood. On this basis, the aim of our study was to evaluate cerebrovascular risk factor prevalence in diabetic stroke patients in comparison with non-diabetics, to analyze whether diabetics have a different prevalence of stroke subtypes as classified by the TOAST classification, and determine whether diabetics and non-diabetics have a different prognosis.Methods and resultsWe enrolled 102 diabetics and 204 non-diabetic subjects with acute ischemic stroke, matched by sex and age (± 3 years). We used as outcome indicators the Scandinavian Stroke Scale (SSS) score at admission and the modified Rankin disability scale at discharge and at a 6-month follow-up. We classified ischemic stroke according to the TOAST classification.Diabetes was associated with lacunar ischemic stroke subtype, with a record of hypertension, and with a better SSS score at admission. The association of diabetes with lacunar stroke remained significant even after adjustment for hypertension or for large artery atherosclerotic and cardioembolic stroke subtypes.ConclusionOur study shows some significant differences in acute ischemic stroke among diabetics in comparison with non-diabetics (higher frequency of hypertension, higher prevalence of lacunar stroke subtype, lower neurological deficit at admission in diabetics).     

Low ankle-brachial index predicts early risk of recurrent stroke in patients with acute cerebral ischemia

ObjectiveLow Ankle-Brachial Blood Pressure Index (ABI) identifies patients with symptomatic and asymptomatic peripheral arterial disease (PAD). We sought to investigate the association of low ABI with early risk of stroke recurrence in patients with acute cerebral ischemia (ACI) and without history of symptomatic PAD.MethodsConsecutive patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and no previous history of PAD were prospectively evaluated with ABI measurements. Demographic characteristics, vascular risk factors and secondary prevention therapies were documented. An ABI ≤0.90 in either leg was considered as evidence of asymptomatic PAD, and an ABI >0.90 was considered as normal. Patients with elevated ABI (>1.30) were excluded. The outcome of interest was recurrent stroke during 30-day follow-up.ResultsA total of 176 patients with acute cerebral ischemia (mean age 64 ± 14 years, 59.1% men, 76.7% AIS) were evaluated. Asymptomatic PAD was detected in 14.8% (95%CI: 10.2–20.8%) of the studied population. The following factors were independently associated with low ABI on multivariate logistic regression models, after adjustment for potential confounders: coronary artery disease (p = 0.008), diabetes mellitus (p = 0.017) and increasing age (p = 0.042). The cumulative 30-day recurrence rate was higher in patients with low ABI (19.2%; 95%CI: 4.1–34.3) compared to the rest (3.3%; 95%CI: 0.4–6.2%; p = 0.001). Atherothrombotic stroke (ASCO grade I; p < 0.001), increasing age (p = 0.002) and low ABI (p = 0.004) were independent predictors of stroke recurrence on multivariate Cox regression models adjusting for confounders.ConclusionsLow ABI appears to be associated with a higher risk of early recurrent stroke in patients with ACI and no history of symptomatic PAD.     

Temporal profile and prognostic value of Lp-PLA2 mass and activity in the acute stroke setting

BackgroundLp-PLA2 is a novel biomarker in cardiovascular diseases due to its ability to predict first-ever and recurrent stroke. Little information is known regarding its influence on early outcome after stroke.ObjectivesWe aimed to investigate Lp-PLA2 in t-PA-treated stroke patients and to study its relationship with early outcome.MethodsLp-PLA2 mass and activity were measured in 135 healthy controls and also in stroke patients treated with t-PA at baseline (n = 99) and serially thereafter (n = 34) by means of the PLAC test at an automated Olympus analyzer and by a colorimetric activity method (diaDexus). NIHSS scores and TCD recordings were also obtained serially. Outcome was defined according to early neurological status, the presence of arterial recanalization and functional outcome at third month.ResultsLp-PLA2 mass was increased as compared to controls, whereas Lp-PLA2 activity was significantly decreased at baseline as compared with controls and with 1 and 24 h determinations. Lp-PLA2 mass and activity were not related with early (48 h) neurological status. Regarding recanalization, higher mass and activity were found among patients who did not achieve complete recanalization by the end of t-PA treatment (p = 0.029 for mass, p = 0.044 for activity). Lp-PLA2 mass and the existence of a proximal occlusion at baseline were the most powerful predictors for persistent occlusions (OR for proximal occlusion 6.8. p = 0.036, OR for Lp-PLA2 mass 7.2 per standard deviation increase, p = 0.008).ConclusionsSignificant changes in Lp-PLA2 concentrations occur early after stroke onset. Lp-PLA2 mass may add relevant information regarding early arterial recanalization in intravenous t-PA-treated stroke patients.     

Serum copper as a marker of inflammation in prediction of short term outcome in high risk patients with chronic heart failure

BackgroundOxidative process and inflammation are regarded as important factors in the pathogenesis of chronic heart failure. Our study was aimed at investigating the prognostic value of serum copper levels in high risk subjects with chronic heart failure.MethodsSerum copper levels and other prognostic indicators were determined in the group of 60 patients with chronic heart failure due to ischemic heart disease: 30 consecutive subjects with acute decompensation of chronic heart failure (acute group A) and 30 patients with chronic stable heart failure (group B). Patients were followed prospectively 12 months. Primary end-point was the mean time to death and/or heart failure hospital admission.ResultsThe mean time to death was in the group A 279.4 ± 18.9 days and 351.7 ± 13.6 days in the group B (p < 0.0001). Cox proportional hazard model revealed that the time to death for all subjects (n = 60) was affected by cardiothoracic ratio (p < 0.001). The time to combined end-point death or hospital admission was affected by serum copper concentration (p < 0.0001).ConclusionSerum copper levels predicted short term outcome in high risk patients with chronic heart failure.     

Coronary bare metal stent implantation in homozygous LDL receptor deficient swine induces a neointimal formation pattern similar to humans

ObjectiveMethylarginines have been shown to interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA, and monomethylarginine, NMMA) and the cellular l-arginine uptake system (ADMA, NMMA and symmetric dimethylarginine, SDMA), thereby causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in diverse populations.MethodsWe investigated whether methylarginines are predictors of mortality in 394 patients after acute ischemic stroke during 7.4 years of follow-up.ResultsPatients who died (N = 231) were older and more frequently had one of the traditional risk factors for stroke (previous stroke/TIA, atrial fibrillation, prevalent ischemic heart disease, peripheral vascular disease, each p < 0.05). ADMA (0.52 μmol/l vs. 0.50 μmol/l, p = 0.015) and SDMA (0.56 μmol/l vs. 0.43 μmol/l, p < 0.001) were higher in patients who died. In multivariable-adjusted hazard models, SDMA but not ADMA or NMMA was an independent predictor of all-cause mortality after stroke (SDMA, hazard ratio 2.41 (1.55–3.72), p < 0.001; ADMA, hazard ratio 1.43 (0.99–2.07), p = 0.06). SDMA was significantly associated with atrial fibrillation (0.55 μmol/l vs. 0.50 μmol/l, p = 0.03) but there was no significant interaction between SDMA and AF in relation to mortality (p = 0.81). SDMA remained significantly associated with mortality after adjusting for eGFR and also additionally adjusting for C-reactive protein, albumin, β-thromboglobulin, and von Willebrand factor.ConclusionOur study demonstrates that SDMA is an independent predictor of total mortality after acute stroke irrespective of renal function. SDMA is associated with atrial fibrillation, endothelial and platelet activation, and may therefore play a previously unknown role in the pathophysiology of stroke.     

Independent prognostic value of C-reactive protein and coronary artery disease extent in patients affected by unstable angina

BackgroundPrevious studies have reported conflicting results on the association between C-reactive protein (CRP) and extent of atherosclerosis, suggesting that the association between CRP and outcome in patients with acute coronary syndromes is independent of coronary artery disease extent. We tested this hypothesis in a selected population of patients with unstable angina undergoing coronary angiography.MethodsNinety-seven consecutive patients with unstable angina were enrolled in this single-centre study. All patients underwent coronary angiography. CRP was measured by an ultrasensitive nephelometric method. We also measured serum levels of soluble CD40 ligand by ELISA and plasma fibrinogen levels by use of the Clauss method. Atherosclerotic disease severity and extent were assessed by angiography using the Bogaty score. The extent index refers to the proportion of the coronary tree affected by detectable atheroma on angiography. The primary end-point at 6 months was a composite of: (a) death, (b) myocardial infarction, and (c) recurrence of unstable angina requiring hospitalization. Cardiac death was the secondary end-point.ResultsNo significant correlation was found between baseline CRP serum levels and angiographic measures of atherosclerotic disease severity and extent, whereas a trend for a significant correlation was found between soluble CD40 ligand and extent index (p = 0.06). Diabetic patients exhibited a higher extent index compared to non-diabetic patients (0.94 ± 0.1 versus 0.7 ± 0.04, p = 0.04). Predictors of primary end-point at both univariate and multivariate analysis were: extent index (p = 0.04 and 0.04, respectively), CRP levels (p = 0.05 and 0.02, respectively), and lack of revascularization (p = 0.03 and 0.02, respectively). Fibrinogen levels were the only independent predictor of cardiac death at follow-up (p = 0.04).ConclusionIn this study we demonstrate that in patients with unstable angina, CRP serum levels and coronary atherosclerosis are not correlated, but both are independently associated with a worse outcome at 6-month follow-up.     

Stress hyperglycemia and acute ischemic stroke in-hospital outcome

Background and AimsStress hyperglycemia is frequent in patients with acute ischemic stroke. However, it is unclear whether stress hyperglycemia only reflects stroke severity or if it is directly associated with adverse outcome. We aimed to evaluate the prognostic significance of stress hyperglycemia in acute ischemic stroke.MethodsWe prospectively studied 790 consecutive patients who were admitted with acute ischemic stroke (41.0% males, age 79.4 ± 6.8 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Stress hyperglycemia was defined as fasting serum glucose levels at the second day after admission ≥ 126 mg/dl in patients without type 2 diabetes mellitus (T2DM). The outcome was assessed with adverse outcome rates at discharge (modified Rankin scale between 2 and 6) and with in-hospital mortality.ResultsIn the total study population, 8.6% had stress hyperglycemia. Patients with stress hyperglycemia had more severe stroke. Independent predictors of adverse outcome at discharge were age, prior ischemic stroke and NIHSS at admission whereas treatment with statins prior to stroke was associated with favorable outcome. When the NIHSS was removed from the multivariate model, independent predictors of adverse outcome were age, heart rate at admission, prior ischemic stroke, log-triglyceride (TG) levels and stress hyperglycemia, whereas treatment with statins prior to stroke was associated with favorable outcome. Independent predictors of in-hospital mortality were atrial fibrillation (AF), diastolic blood pressure (DBP), serum log-TG levels and NIHSS at admission. When the NIHSS was removed from the multivariate model, independent predictors of in-hospital mortality were age, AF, DBP, log-TG levels and stress hyperglycemia.ConclusionStress hyperglycemia does not appear to be directly associated with the outcome of acute ischemic stroke. However, given that patients with stress hyperglycemia had higher prevalence of cardiovascular risk factors than patients with normoglycemia and that glucose tolerance was not evaluated, more studies are needed to validate our findings.     

The coexistence of heart failure predicts short term mortality, but not disability, in patients with acute ischemic stroke treated with thrombolysis: The Florence area Registry

BackgroundThrombolysis in ischemic stroke reduces disability but not mortality. Our aim was to evaluate the predictivity of heart failure (HF) diagnosis on 90-day mortality and disability in stroke patients undergoing thrombolysis.Material and methodsHospital records of all consecutive stroke patients treated with thrombolysis at our University Hospital were reviewed. Clinical assessment for HF and echocardiogram were available for all patients according to the thrombolysis institutional protocol. History of HF, LVEF < 40%, or BOSTON score ≥ 5 were tested as predictors.ResultsOf 130 patients (age 66 ± 14 years, 64.6% males, baseline NIHSS 15.6 ± 8.8), 17 (13.1%) had a history of HF, 16 (12.7%) a BOSTON score ≥ 5, 13 (10.9%) a LVEF < 40% and 24 (19.0%) met clinical criteria for HF diagnosis. Ninety-day mortality and incidence of disability were 16.1% and 36.1%, respectively. After adjustment for age, sex, baseline stroke severity and pre-stroke disability, LVEF < 40% and clinical diagnosis of HF were predictors of 90-day mortality, (p = 0.007 and p = 0.037, respectively).ConclusionClinical diagnosis of HF predicts mortality, but not disability, in acute stroke patients undergoing thrombolysis. Unlike anamnestic record of HF, clinical evaluation of cardiac function, with estimation of LVEF, predicts mortality.     

High plasma HDL-C attenuates stress hyperglycemia during acute phase of myocardial infarction

ObjectiveDuring myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia, which is followed by a substantial increase in mortality. Recent findings in cellular models indicate that HDL may act on glucose homeostasis by improving insulin sensitivity and secretion. In this study, we explored this potential effect in patients during the acute phase of MI.MethodsPlasma glucose, insulin and C-peptide were measured at admission in the first 24 h and on the fifth day after MI with ST-segment elevation in 183 consecutive non-diabetic patients. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31–38, Q3: 38–47 and Q4: >47 mg/dL). The Homeostasis Model Assessment version 2 was used to assess insulin sensitivity (HOMA2S) and beta-cell function (HOMA2B).ResultsOn admission, no difference was found between the quartiles in glucose (p = 0.6), insulin (p = 0.6) or C-peptide (p = 0.5) levels, HOMA2S (p = 0.9) or HOMA2B (p = 1.0). On the fifth day there was a reduction in glucose levels whose intensity was directly proportional to the HDL-C quartile (p < 0.001). At the same time, there was a reduction in plasma insulin (p < 0.001) and C-peptides (p < 0.001) whose magnitude was inversely proportional to the HDL-C quartile. Consistently, the increase of HOMA2S (p < 0.001) and HOMA2B (p = 0.01) were also positively associated with HDL-C levels. Furthermore, plasma HDL-C levels were inversely and independently associated with blood glucose change during the acute phase.ConclusionThis study demonstrates the association between low plasma HDL-C levels and increased duration of stress hyperglycemia during MI and suggests in humans the interaction between HDL and insulin secretion and sensitivity.     

Coronary stenting is associated with an acute increase in plasma myeloperoxidase in stable angina patients but not in patients with acute myocardial infarction

BackgroundMyeloperoxidase (MPO) has emerged as a critical mediator in the physiopathology of atherosclerosis from plaque formation and growth until destabilization and rupture leading to acute coronary syndrome (ACS). Using coronary stenting as a model of plaque injury, we aimed to determine the evolution of systemic MPO levels following coronary stenting in stable angina patients and in patients with acute myocardial infarction (AMI).MethodsPlasma levels of MPO, lactoferrin, interleukin (IL)-6, C-reactive protein and PMN counts were assessed in 13 patients with Non-ST-elevation myocardial infarction (NSTEMI) (Group A) and in 29 patients with stable angina pectoris (Group B), undergoing coronary stenting. Serial blood samples were taken before angioplasty (baseline) and at 1, 6 and 24 h following initial balloon inflation.ResultsFollowing angioplasty, the overall plasma MPO levels significantly increased at 1 h in group B (120.5 ± 79.0 to 166 ± 79.5, p = 0.003) but not in group A (121 ± 63.4 to 124.7 ± 76.9, p = 0.753). In Group B, the increase in MPO levels at 1 h were significantly higher in the presence of complex lesions compared to patients with simple lesions (p = 0.023). Lactoferrin levels showed no change over time except for a significant decrease at 6 h in group B.ConclusionsIn stable angina patients, coronary stenting is associated with an acute and transient increase in plasma MPO levels, but not in lactoferrin levels, with an enhanced response in the presence of complex lesions. In contrast, we observed no changes in plasma MPO and lactoferrin levels following stenting in patients with AMI. Given its pro-inflammatory properties, the potential implication of MPO release on clinical outcome in stable patients undergoing stenting needs further investigation.     

Clinical outcomes of acute ischemic stroke patients treated by direct catheter-based trombectomy depending on their baseline characteristics

BackgroundDirect catheter-based thrombectomy (d-CBT) was proven to be an effective treatment for proximal occlusions of the major intracranial arteries in acute stroke patients. The aim of this study was to compare clinical outcomes of patients treated by d-CBT depending on their baseline characteristics.MethodsA single center, prospective, observational registry of consecutive patients (pts) treated by d-CBT for an acute ischemic stroke. The degree of dependence after a stroke was measured by the modified Rankin scale (mRS) at 3 months follow-up and pts were divided into 2 subgroups based on functional independence/dependence (mRS 0–2 vs. 3–6).ResultsA total of 111 consecutive patients (mean age 65.9 ys, men 55%) have been enrolled. A favorable outcome (mRS ≤ 2 at 3 months) was reached in 39.8% (44 pts). The pts with favorable outcome (mRS ≤ 2) compared to pts with poor outcome (mRS 3–6) were younger (61 ys vs. 70 ys, p < 0.01), had higher prevalence of cigarette smoking (45.5% vs. 25.4%, p < 0.002) and had lower prevalence of known atrial fibrilation (25% vs. 53.7%, p < 0.001). There were no significant differences between the subgroups in: sex (men 50% vs. 58%, p = 0.27), body mass index (27.8 vs. 29.2, p = 0.21), arterial hypertension (70.5% vs. 77.6%, p = 0.26), diabetes mellitus (15.9% vs. 25.4%, p = 0.15), chronic kidney disease (11.4% vs. 22.4%, p = 0.08) and NIHSS on admission (15 vs. 18, p = 0.69).ConclusionsMechanical thrombectomy achieved better clinical results in younger patients, in smokers and in patients with stroke not caused by atrial fibrillation.     

Serum albumin as a determinant of cortisol release in patients with acute ischemic stroke

ObjectiveAnimal studies demonstrated that protein malnutrition increases pituitary-adrenorcortical activity and leads to excessive cortisol release. The aim of our study was to determine the association between serum albumin and cortisol level in patients with acute ischemic stroke.MethodsFifty-nine patients with first-ever ischemic stroke were included. Serum albumin level was measured within 36 h after stroke symptoms onset. Serum cortisol was measured between 36 and 72 h after stroke onset at 6 a.m., 10 a.m., 6 p.m. and 10 p.m.ResultsThe patients in upper tertile of serum albumin had significantly lower cortisol level measured at 6 a.m. (median with interquartiles: 549.0 [430.4–667.7] nmol/L vs 590.4 [482.8–918.7] nmol/L, P = 0.047) and 10 a.m. (402.8 [344.9–510.4] nmol/L vs 634.6 [482.8–827.7] nmol/L, P < 0.01) than patients in lower and middle tertiles. On logistic regression analysis adjusted for age and stroke severity, patients in lower and middle tertile of serum albumin had about 7-times higher risk of hypercortisolemia than patients in upper tertile (P < 0.01).ConclusionsLow serum albumin level in patients with ischemic stroke is associated with higher serum cortisol level and predisposes to hypercortisolemia.     

Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X

ObjectivesMarkers of non-specific inflammation, such as C-reactive protein (CRP) or leukocyte count are increased in end-stage renal disease patients. Recent studies have shown positive associations between inflammatory markers and cardiovascular mortality in kidney transplant recipients, but these analyses had been limited by sample size. The aim of our study was to determine the association between pretransplant CRP levels and leukocyte counts with posttransplant outcome in a prospectively enrolled cohort of kidney transplant recipients.Methods459 consecutive patients transplanted from July 1995 to December 2007 were analyzed. Both markers were obtained prior to transplantation and patients were grouped according to baseline CRP levels (<5 mg/l or ≥5 mg/l) or leukocyte counts (<10,000/μl or ≥10,000/μl).ResultsMajor cardiac events were associated with elevated pretransplant CRP levels (p < 0.00003) but not leukocyte counts. Furthermore, more acute rejection episodes within 4 weeks or 6 months, as well as a lower probability of survival at 6 months were found in patients with elevated pretransplant CRP levels or leukocyte counts.ConclusionElevated pretransplant serum CRP level is a risk predictor for major cardiac events in renal transplant patients. It is also predictive, besides leukocyte counts, for acute rejection episodes. Elevated CRP levels and initial high leukocyte counts may prove to be useful markers for posttransplant course and warrant the close follow-up of such patients.     

High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction

ObjectiveEnhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event.MethodsConsecutive patients (n = 372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type α (TNF-α), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up.ResultsThe decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-α and CRP less intense during the first 5 days in LS than in HS patients (p < 0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r = 0.46; p < 0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p < 0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p < 0.05).ConclusionExcessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI.     

The plasma concentration of Lpa-I:A-II particles as a predictor of the inflammatory response in patients with ST-elevation myocardial infarction

ObjectiveTo investigate the relationship between plasma HDL at admission and the extent of the inflammatory response during an ST-elevation myocardial infarction (STEMI), and to analyse structural HDL changes during STEMI as related to the extent of inflammation.Methods and resultsCRP and IL-6 were monitored for 96 h in 45 patients with STEMI. Plasma apoA-II and LpA-I:A-II levels at admission, but not HDL cholesterol or other HDL-related biomarkers, were associated with the extent of the inflammatory response during STEMI, as indicated by the positive correlations with CRP AUC (apoA-II: F = 7.44, p = 0.009; LpA-I:A-II: F = 14.29, p < 0.001), and IL-6 AUC (apoA-II: F = 6.98, p = 0.012; LpA-I:A-II: F = 6.67, p = 0.013). By multivariate analysis the plasma LpA-I:A-II level at admission was a powerful independent predictor of the inflammatory response, evaluated either as CRP AUC (F = 22.30, p < 0.001), or IL-6 AUC (F = 6.92, p = 0.012). During STEMI, the plasma concentration of LpA-I:A-II, but not LpA-I particles decreased, HDL became larger and progressively enriched in serum amyloid A; these changes occurred only in patients with a significant inflammatory response.ConclusionAn elevated plasma concentration of LpA-I:A-II particles was an independent predictor of a more severe inflammatory response in patients with STEMI.     

Variants within the nitric oxide synthase 1 gene are associated with stroke susceptibility

ObjectiveAnimal studies have allowed important insights into the role of the nitric oxide synthase (NOS) enzymes in atherosclerosis and hypertension, as well as in stroke. In this study we tested the hypothesis that the NOS1 and NOS3 genes, respectively encoding neuronal NOS (nNOS) and endothelial NOS (eNOS), influence stroke susceptibility and outcome after a stroke event.MethodsWe conducted a case–control association study in 551 ischemic stroke patients and 530 controls to assess the role of NOS1 and NOS3 variants in stroke susceptibility. The same genes were tested for association with stroke outcome in a subset of 431 patients.ResultsFour NOS1 single nucleotide polymorphisms (SNPs) (rs2293050, rs2139733, rs7308402 and rs1483757) and four haplotypes were significantly associated with stroke susceptibility after adjusting for demographic, clinical and life-style risk factors, and correcting for multiple testing using the false discovery rate (FDR) method (SNPs: 0.004 < _uncorrected P < 0.007 and 0.036 < FDR q < 0.048; haplotypes: 0.001 < _uncorrected P < 0.010 and 0.018 < FDR q < 0.032). NOS1 variants were not associated with stroke outcome. We did not find any evidence for a role of the NOS3 gene in stroke susceptibility or outcome.ConclusionOur results highlight NOS1 as a susceptibility factor for stroke, but do not corroborate previous NOS3 association findings with stroke risk. nNOS is known to play a major role in atherosclerosis development and in blood flow regulation, and it is plausible that its influence in stroke may be mediated through these two main clinical risk factors.     

Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction

ObjectivePregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients.MethodBlood samples were drawn at study entry. Serum PAPP-A values ≥4 mIU/L were considered elevated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction.ResultsPatients (n = 4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62–2.45, p < 0.0005), all-cause mortality (HR 2.42, 1.92–3.06, p < 0.0005), and myocardial infarction (HR 1.40, 1.01–1.94, p = 0.046). After Holm's correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22–1.86, p < 0.0005) and all-cause mortality (HR 1.68, 1.32–2.13, p < 0.0005).ConclusionIn patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death.