HDL-inflammatory index correlates with poor outcome in hemodialysis patients

Oxidative stress and cardiovascular disease are risk factor of patients with chronic kidney disease (CKD) on maintenance hemodialysis. We used the fluorescence of low-density lipoprotein as an index of its proinflammatory potential to examine any role that high-density lipoprotein (HDL) might have in promoting this effect. The total body fat of the patients was measured by means of near-infrared interactance and their quality of life by means of SF36 questionnaires. In 189 randomly selected patients, followed for 30 months, HDL was found to be significantly anti-inflammatory but with a large standard deviation. Fully 17% of the patients had a decidedly proinflammatory index along with inferior SF36 scores. The patients were divided into 10% increments of total body fat percentages up to 40%. HDL was found to be progressively proinflammatory the higher the body fat content. Patients with a higher HDL proinflammatory index had a higher 30-month adjusted hazard ratio for death than those whose HDL were seen to be anti-inflammatory. Our findings suggest an important role of inflammatory HDL in patients with CKD leading to poor outcome

Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value.OBJECTIVE This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers.METHODS The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2.RESULTS Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes.CONCLUSION M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family

HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease

BACKGROUND AND AIMS: We have previously shown that the anti-inflammatory and anti-oxidant functions of HDL are impaired in T2D patients. In this study, we examined whether HDL from T2D patients contains elevated levels of oxidized fatty acids and whether those levels correlate with cardiovascular disease (CVD). METHODS AND RESULTS: HETEs and HODEs on HDL were determined by LC-MS/MS in 40 non-diabetic controls (ND), 40 T2D without CVD (D(+)CVD(−)) and 38 T2D with known history of CVD (D(+)CVD(+)). HDL oxidant index was evaluated by a cell-free assay using dichlorofluorescein. Twenty-six randomly selected subjects from the three groups underwent coronary calcium score evaluation (CAC). Major cardiovascular risk factors were similar among the groups. HETEs and HODEs content were significantly increased in HDL from D(+)CVD(+) when compared to D(+)CVD(−) and ND patients. HDL oxidant index was not different among the three groups; however, it was significantly higher in patients with CAC score >100 when compared to patients with CAC score <100. CONCLUSION: Patients with D(+)CVD(−) and D(+)CVD(+) are characterized by a severe, graded enrichment of oxidized fatty acids on HDL. In the present study, a loss of HDL function (as estimated by the HDL oxidant index) is observed only in patients with more advanced atherosclerosis