Apolipoprotein E in VLDL and LDL With Apolipoprotein C‐III is Associated With a Lower Risk of Coronary Heart Disease

Background: Low‐density lipoprotein (LDL) with apolipoprotein C‐III (apoC‐III) is the lipoprotein species that most strongly predicts initial and recurring coronary heart disease (CHD) events in several cohorts. Thus, a large portion of the CHD risk conferred by LDL may be attributable to LDL that contains apoC‐III. Very‐low‐density lipoprotein (VLDL) and LDL with apoC‐III have varying amounts of apoE. We hypothesized that a high content of apoE lessens the adverse influence of apoC‐III on the risk of CHD because it promotes the clearance of VLDL and LDL from plasma. Methods and Results: We studied 2 independent cohorts, the Nurses' Health Study, composed of women, and the Health Professionals Follow‐up Study, composed of men. These cohorts contributed to this study 322 women and 418 men initially free of CVD who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow‐up and matched controls who remained free of CHD. The apoE content of LDL with apoC‐III was inversely associated with CHD after multivariable adjustment (relative risk for top versus bottom quintile 0.53, 95% CI 0.35 to 0.80). The apoE content of VLDL with apoC‐III had a similar inverse association with CHD. The highest risks were associated with a high apoB concentration and a low apoE content of LDL with apoC‐III or of VLDL+LDL with apoC‐III. The observed associations were in both male and female cohorts and independent of traditional CHD risk factors and of C‐reactive protein. Conclusions: An increased apoE content in VLDL and LDL with apoC‐III was associated with a lower risk of CHD. Strategies to enrich VLDL and LDL in apoE are worth exploring for the prevention of CHD

Case report: desensitization of hypersensitivity against the antisense oligonucleotide volanesorsen

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder that causes extremely elevated plasma triglyceride levels, with limited therapeutic options. Volanesorsen is an antisense oligonucleotide approved for its treatment. A 24-year-old woman with genetically diagnosed FCS secondary to a pathogenic variant in APOA5 and a history of recurrent hypertriglyceridemia-induced pancreatitis episodes was being treated with volanesorsen, 285 mg every 2 weeks. Treatment with volanesorsen achieved normalization of triglycerides to <200 mg/dl. However, after the fifth dose of the medication, the patient developed urticaria and volanesorsen was discontinued. In the absence of alternative pharmacological treatments, the patient received a novel desensitization protocol for volanesorsen that allowed continuation of therapy, without evidence of hypersensitivity reactions after subsequent administrations. FCS requires aggressive multimodal therapy and close follow-up. Volanesorsen has shown great efficacy, but a significant rate of discontinuation due to side effects has been observed. Here, the patient presented an immediate hypersensitivity reaction to volanesorsen, but the provision of a desensitization protocol was effective, facilitating continued treatment and impacting the survival and quality of life of the patient

Case report: desensitization of hypersensitivity against the antisense oligonucleotide volanesorsen

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder that causes extremely elevated plasma triglyceride levels, with limited therapeutic options. Volanesorsen is an antisense oligonucleotide approved for its treatment. A 24-year-old woman with genetically diagnosed FCS secondary to a pathogenic variant in APOA5 and a history of recurrent hypertriglyceridemia-induced pancreatitis episodes was being treated with volanesorsen, 285 mg every 2 weeks. Treatment with volanesorsen achieved normalization of triglycerides to &lt;200 mg/dl. However, after the fifth dose of the medication, the patient developed urticaria and volanesorsen was discontinued. In the absence of alternative pharmacological treatments, the patient received a novel desensitization protocol for volanesorsen that allowed continuation of therapy, without evidence of hypersensitivity reactions after subsequent administrations. FCS requires aggressive multimodal therapy and close follow-up. Volanesorsen has shown great efficacy, but a significant rate of discontinuation due to side effects has been observed. Here, the patient presented an immediate hypersensitivity reaction to volanesorsen, but the provision of a desensitization protocol was effective, facilitating continued treatment and impacting the survival and quality of life of the patient

Young Hispanics at risk of type 2 diabetes display endothelial activation, subclinical inflammation and alterations of coagulation and fibrinolysis

Background: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it. Methods: We studied 36 young Hispanic adults without diabetes (ages 18–40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups. Results: Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese. Conclusions: Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease

Impacto do exercício sobre o metabolismo dos lipídeos e da dislipidemia

The chronic practice of exercise induces a series of cellular and organismal adaptations that modify the way the human body metabolizes all macronutrients, including lipids. Endurance exercise and resistance exercise elicit different responses that result in differential effects on lipid and lipoprotein metabolism. These effects are quantitatively and qualitatively different and mediated by distinct signaling pathways. In this review, we summarize relevant evidence on the impact of exercise on lipid and lipoprotein metabolism, and finalize with some practical recommendations on exercise practice for patients with dyslipidemia in the primary care settingLa práctica crónica del ejercicio induce una serie de adaptaciones celulares y orgánicas que modifican la forma en que&nbsp;el cuerpo humano metaboliza todos los macronutrientes, incluidos los lípidos. El ejercicio de duración y el ejercicio de resistencia provocan diferentes respuestas que resultan en efectos diferenciales sobre el metabolismo de los lípidos y las lipoproteínas. Estos efectos son cuantitativa y&nbsp;cualitativamente diferentes y mediados por distintas vías de&nbsp; señalización. Esta revisión, resume la evidencia pertinente sobre la repercusión del ejercicio en el metabolismo de los lípidos y las lipoproteínas, y finaliza con algunas recomendaciones sobre la práctica del ejercicio para los pacientes con dislipidemia en el ámbito de la atención primariaA prática crônica de exercício induz uma série de adaptações celulares e orgânicas que modificam a maneira pela qual o corpo humano metaboliza todos os macronutrientes, incluindo os lipídios. O exercício de duração e o exercício de resistência provocam diversas respostas que resultam em efeitos diferenciais no metabolismo de lipídios e lipoproteínas. Estes efeitos são quantitativa e qualitativamente distintos e mediados por diferentes vias de sinalização. Nesta revisão, se resume as evidências relevantes sobre o impacto do exercício no metabolismo de lipídios e das lipoproteínas e conclui, com algumas recomendações sobre a prática de exercícios para pacientes com dislipidemia no campo da atenção primári

Depression and microvascular complications predict poor goal achievement among Colombian patients with type 2 diabetes

Aims: Many patients with type 2 diabetes (DM2) in Latin American countries remain insufficiently controlled. We aimed to identify factors associated with persistent poor metabolic control in Colombian patients with DM2. Methods: Retrospective one-year follow-up cohort study of adult patients with DM2. The primary outcome was persistent poor metabolic control (PPMC): HbA1c level >8% in all measurements during follow-up. Secondary outcomes were intermittent poor metabolic control (IPMC) and good control (GC: simultaneous achievement of HbA1c, blood pressure and LDL cholesterol goals). Multiple demographic, clinical and laboratory variables were predictors in multivariable logistical models. Results: Of 399 patients included, 50 had the primary endpoint during follow-up. Older age was negatively associated with PPMC (OR 0.40, 95%CI 0.17-0.92 for extreme quartiles), even after multivariate adjustment. Depression and the presence of multiple microvascular complications were strongly associated with the secondary endpoint IPMC (multivariate OR respectively 4.2, 95%CI 1.08-16.4 for depression; 5.61, 95%CI 1.03-30.6 for microvascular complications). Being unemployed was associated with significantly less odds of achieving GC (multivariate OR 0.19, 95%CI 0.04-0.95). Conclusions: Age, depression, the presence of microvascular complications and employment status were associated with the success or failure of diabetes management. These factors were better correlates of therapeutic success than the pharmacological agent employed

Metabolic Hormones, Apolipoproteins, Adipokines, and Cytokines in the Alveolar Lining Fluid of Healthy Adults: Compartmentalization and Physiological Correlates

Objectives: Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF), compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier. Research Design and Methods Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines) using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values. Results: ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity. Conclusions: Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of healthy individuals. For the proteins measured, charge may influence trafficking and compartmentalization to the alveolar airspace more than molecular weight or hydrophobicity. These data may have implications for homeostasis and drug delivery to the lung

Postprandial determination of Apo B-48 levels in whole plasma of healthy young individuals by a double-sandwich ELISA

ResumenHigh postprandial concentrrations of chylomicrons and its remnants are correlated with an atherosclerosis progression. Apolipoprotein B-48 is an essential component of these lipoproteins and appears to be a suitable marker for clinical studies of postprandial lipid metabolism and its relationship to cardiovascular risk.[Mantilla G, Sierra ID, Medivil CO, P&eacute;res CE. Postprandial determination of Apo B-48 levels in whole plasma of healthy young individuals by a double-sandwich ELISA. MedUNAB 2003; 6:130-6].Key words: Apo B-48, postprandial lipemia, cardiovascular risk, immunoassay, chylomicrons, lipoproteins

Concentrations of hormones and cytokines in serum and alveolar lining fluid.

<p>Proteins are ranked from the highest to the lowest concentration in ALF, after adjustment for dilution during the lavage procedure. Data are median (Q1, Q3).</p><p>^a Fourteen of the subjects had values of 0 and 10 had values ranging from 92.2 to 4,615.</p><p>Concentrations of hormones and cytokines in serum and alveolar lining fluid.</p

Concentrations of hormones and cytokines in serum and alveolar lining fluid.

<p>Proteins are ranked from highest to lowest ALF / serum concentration, after adjustment for dilution during the lavage procedure. Data are median (Q1, Q3). P-value is for the difference between median concentrations in serum and median concentrations in ALF, from Wilcoxon′s signed-rank test. Proteins are sorted from the most to the least concentrated in ALF relative to serum.</p><p>Concentrations of hormones and cytokines in serum and alveolar lining fluid.</p