Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study.

BACKGROUND: It is important to identify patients at increased risk of worsening of left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). We aimed to identify the association of various potential biomarkers with LVEF impairment after an MI in South American patients. METHODS: We studied adult patients admitted to a University Hospital and diagnosed with an acute MI. Plasma concentrations of high-sensitivity C-reactive protein (hsCRP), proprotein convertase subtilisin/kexin type 9 (PCSK9), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and heart-type fatty-acid-binding protein (FABP3) were determined in samples drawn shortly after the event. Participants had a follow-up visit at least 45 days after the event. The primary endpoint was defined as any decline in LVEF at follow-up relative to baseline. RESULTS: The study included 106 patients (77.4% men, 22.6% women), mean age was 64.1, mean baseline LVEF was 56.6, 19% had a prior MI. We obtained a follow-up evaluation in 100 (94.4%) of participants, mean follow-up time was 163 days. There was a significant correlation between baseline PCSK9 and hsCRP (r = 0.39, p < 0.001). Baseline hsCRP concentrations were higher in patients who developed the endpoint than in those who did not (32.1 versus 21.2 mg/L, p = 0.066). After multivariate adjustment, baseline PCSK9, male sex and age were significantly associated with impairment in LVEF. The absolute change in LVEF was inversely correlated with baseline hsCRP (standardized coefficient = - 0.246, p = 0.004). CONCLUSION: High plasma levels of PCSK9 and hsCRP were associated with early decreases in LVEF after an MI in Latin American patients.

Social inequalities shape diet composition among urban Colombians: The Colombian Nutritional Profiles cross-sectional study.

OBJECTIVE: To explore the influence of socioeconomic position on habitual dietary intake in Colombian cities. DESIGN: We conducted a cross-sectional, population-based study in five Colombian cities. Dietary intake was assessed with a 157-item semi-quantitative food frequency questionnaire previously developed for the Colombian population. Nutrient analysis was performed using national and international food composition tables. Socioeconomic position was assessed with two indicators: a government-defined, asset-based, household-level index called socioeconomic stratum (SES) and, among adults, highest educational level attained. SETTING: The five main urban centers of Colombia: Bogotá, Medellin, Barranquilla, Cali and Bucaramanga. PARTICIPANTS: Probabilistic, multistage sample of 1865 participants (n=1491 for analyses on education). RESULTS: For both sexes, increasing SES was associated with a lower consumption of energy (p-trend <0.001 in both sexes), carbohydrates (p-trend ˂0.001 in both sexes), sodium (p-trend=0.005 in males, <0.001 in females), saturated fatty acids (p-trend <0.001 in both sexes) and among females, cholesterol (p-trend=0.002). More educated men consumed significantly less energy and carbohydrates (p-trend=0.036 and ˂0.001, respectively). Among men, intake of trans fats increased monotonically with educational level, being 21% higher among college graduates relative to those with only elementary education (p-trend=0.023). Among women, higher educational level was associated with higher MUFA intake (p-trend=0.027). CONCLUSIONS: SES and educational level are strong correlates of the usual diet of urban Colombians. Economically deprived and less educated segments of society display dietary habits that make them vulnerable to chronic diseases and should be the primary target of public health nutrition policies.

ApoE and apoC-III-defined HDL subtypes: a descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity.

BACKGROUND: The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. METHODS: Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E + C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E + C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting. RESULTS: HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6% of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8, 12.2 and 8.37% of plasma LCAT respectively for E + C-, E-C+ and E + C+). LCAT mass was lower in E + C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r = - 0.55, P = 0.017) and E-C- alpha 1 HDL (r = - 0.49, P = 0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r = 0.52, P = 0.025). CONCLUSIONS: The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.

NEW BIOTECHNOLOGICAL TREATMENTS FOR LIPID DISORDERS.

Disorders of lipid and lipoprotein metabolism play a central role in the pathogenesis of atherosclerotic cardiovascular diseases (CVDs). Despite the widespread use of efficacious lipid-modifying therapies, the residual risk of CVD remains unacceptably high. The purpose of this manuscript is to review the application of new technologies in the treatment of lipid disorders. New therapies work mostly at the gene expression level and are, therefore, different from traditional small-molecule drugs that work mainly by inhibiting already synthesized proteins. We will briefly lay out the function of the gene products targeted by the new agents. Then, we will organize our review of new biotechnological treatments by the molecular approach, namely: monoclonal antibodies, antisense oligonucleotides, small-interfering RNAs, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9)-based genome editing. The paper concludes with the description of the current clinical studies and the perspectives for the use of these agents. (REV INVEST CLIN. 2018;70:244-54).

Novel Pathways of Apolipoprotein A-I Metabolism in High-Density Lipoprotein of Different Sizes in Humans.

OBJECTIVE: A prevailing concept is that high-density lipoprotein (HDL) is secreted into the systemic circulation as a small mainly discoidal particle, which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans. APPROACH AND RESULTS: We studied the metabolism of apolipoprotein A-I in 4 standard HDL sizes by endogenous isotopic labeling in 6 overweight adults with low HDLc and in 6 adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apolipoprotein A-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1 to 4 days and then was cleared. Enlargement of very small and medium to large and very large HDL and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower, whereas medium, large, and very large HDL were cleared faster in the low HDLc group. CONCLUSIONS: A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes across the common range of HDLc concentrations.

Identification and management of prediabetes: results of the Latin America Strategic Prediabetes Meeting.

To understand the status of prediabetes diagnosis and treatment in Latin America and to evaluate the use of metformin for diabetes prevention in this context. A panel of 15 diabetes experts from seven countries in Latin America met on 14 - 15 August 2014 in Lima, Peru, to review the available literature, discuss the role of prediabetes in type 2 diabetes mellitus and cardiovascular disease, analyze collected information, and make conclusions for prediabetes diagnosis and treatment in Latin America. Prediabetes diagnosis, screening, and treatment, including lifestyle changes, pharmacological treatment, and cost-effectiveness were discussed. Five resulting statements were issued for Latin America: prediabetes is a clinical and public health problem; health care systems do not currently diagnose/treat prediabetes; use of prediabetes risk detection tools are needed region-wide; treatment includes lifestyle changes, multidisciplinary education, and metformin; and registries of patient records and further studies should be supported. The expert panel concluded that in Latin America, preventive treatment through lifestyle changes and metformin are cost-effective interventions. It is important to improve prediabetes identification and management at the primary care level.

Comprender el estado del diagnóstico y el tratamiento de la prediabetes en América Latina y evaluar el uso de la metformina para la prevención de la diabetes en este contexto.Un panel de 15 expertos en diabetes de siete países de América Latina se reunió del 14 al 15 de agosto de 2014 en Lima, Perú, para revisar la literatura disponible, discutir el papel de la prediabetes en la diabetes mellitus tipo 2 y la enfermedad cardiovascular, analizar la información recolectada y formular conclusiones para el diagnóstico y el tratamiento de la prediabetes en América Latina.Se analizaron el diagnóstico, el tamizaje y el tratamiento de la prediabetes, inclusive los cambios en el estilo de vida, el tratamiento farmacológico y la relación costo-eficacia. Se emitieron cinco conclusiones para América Latina: la prediabetes es un problema clínico y de salud pública; los sistemas de atención de la salud actualmente no diagnostican o no tratan la prediabetes; el uso de herramientas de detección del riesgo de prediabetes es necesario en toda la región; el tratamiento incluye cambios en el estilo de vida, educación multidisciplinaria y metformina; y se debe brindar apoyo para llevar registros de historias clínicas y realizar estudios adicionales.El panel de expertos concluyó que en América Latina el tratamiento preventivo basado en cambios en el estilo de vida y administración de metformina son intervenciones eficaces en relación al costo. Es importante mejorar la identificación y el manejo de la prediabetes en el nivel de atención primaria.

Entender o estado do diagnóstico e tratamento do prediabetes na América Latina e avaliar o uso de metformina para prevenção de diabetes neste contexto.Um painel de 15 especialistas em diabetes de sete países da América Latina reuniu-se de 14 a 15 de agosto de 2014 em Lima, Peru, para analisar a literatura disponível, discutir o papel do prediabetes em diabetes mellitus tipo 2 e doenças cardiovasculares, analisar informações coletadas e fazer conclusões para o diagnóstico e tratamento do prediabetes na América Latina.O diagnóstico, rastreio e tratamento pré-diabetes, incluindo mudanças de estilo de vida, tratamento farmacológico e custo-efetividade foram discutidos. Foram emitidas cinco conclusões resultantes para a América Latina: o prediabetes é um problema clínico e de saúde pública; os sistemas de saúde atualmente não diagnosticam/tratam prediabetes; o uso de ferramentas de detecção de risco de prediabetes é necessário em toda a região; o tratamento inclui mudanças de estilo de vida, educação multidisciplinar e metformina; e devem ser suportados registros de pacientes e outros estudos.O painel de especialistas concluiu que na América Latina, o tratamento preventivo através de mudanças de estilo de vida e metformina são intervenções efetivas em relação ao custo. É importante melhorar a identificação e gestão do prediabetes no nível de atenção primária.

Multiple apolipoprotein kinetics measured in human HDL by high-resolution/accurate mass parallel reaction monitoring.

Endogenous labeling with stable isotopes is used to study the metabolism of proteins in vivo. However, traditional detection methods such as GC/MS cannot measure tracer enrichment in multiple proteins simultaneously, and multiple reaction monitoring MS cannot measure precisely the low tracer enrichment in slowly turning-over proteins as in HDL. We exploited the versatility of the high-resolution/accurate mass (HR/AM) quadrupole Orbitrap for proteomic analysis of five HDL sizes. We identified 58 proteins in HDL that were shared among three humans and that were organized into five subproteomes according to HDL size. For seven of these proteins, apoA-I, apoA-II, apoA-IV, apoC-III, apoD, apoE, and apoM, we performed parallel reaction monitoring (PRM) to measure trideuterated leucine tracer enrichment between 0.03 to 1.0% in vivo, as required to study their metabolism. The results were suitable for multicompartmental modeling in all except apoD. These apolipoproteins in each HDL size mainly originated directly from the source compartment, presumably the liver and intestine. Flux of apolipoproteins from smaller to larger HDL or the reverse contributed only slightly to apolipoprotein metabolism. These novel findings on HDL apolipoprotein metabolism demonstrate the analytical breadth and scope of the HR/AM-PRM technology to perform metabolic research.

Effect of a nutraceutical combination on sleep quality among people with impaired sleep: a randomised, placebo-controlled trial.

In this randomised, placebo-controlled trial, adults with impaired sleep (Pittsburgh Sleep Quality Index ≥ 5) were randomly assigned using a minimization algorithm to receive a formulation containing L-theanine plus lemon balm, valerian, and saffron extracts, or placebo, during 6 weeks. Objective sleep quality parameters were measured using an actigraphy device. We enrolled and randomised 64 individuals, 31 from the active group and 27 from the placebo group completed the 6 week follow-up. Mean sleep efficiency remained unmodified in the active group, and increased by 3% in the placebo group, the between-group difference in the change was not statistically significant (p = 0.49). Total sleep time also improved more with placebo (13.0 vs. 1.33 min, p = 0.66). Time wake after sleep onset (WASO) decreased more in the active group (4.6% vs. 2.4%), but the difference was not significant (p = 0.33). Mean PSQI decreased by 3.11 points (32.3%) in the active group, and by 3.86 points (39.5%) in the placebo group (p = 0.41). SF-36 increased more with placebo (+ 18.3 in active, + 32.1 in placebo, p = 0.68). Salivary cortisol remained unchanged in both groups. No serious adverse events were reported. Among adults with impaired sleep, a nutraceutical combination did not improve objective or subjective sleep parameters more than a placebo infusion.

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.

Consumption of Sugary Drinks among Urban Adults in Colombia: Association with Sociodemographic Factors and Body Adiposity.

INTRODUCTION: Calories from sugar-sweetened beverages (SSBs) contribute to the development of noncommunicable diseases. There is limited knowledge of the intake of SSBs and their correlates in developing countries. Thus, this study aimed to estimate the consumption of multiple SSBs and their sociodemographic correlates in an urban adult population from Colombia, South America. METHODS: This was a probabilistic, population-level study of adults aged 18 to 75 from five cities representing different regions of Colombia. Dietary intake was assessed employing a 157-item semiquantitative food frequency questionnaire that inquired about intake over the last year. The consumption of regular soda, low-calorie soda, homemade and industrialized fruit juices, energy drinks, sport drinks, malt drinks and traditional sugar cane infusion ("agua de panela") was analyzed for the total sample and subgroups defined by sociodemographic and clinical factors of interest. RESULTS: The study included 1491 individuals (female: 54.2%, mean age: 45.3, overweight: 38.0%, obese: 23.3%). Sugary beverages contributed, on average, 287 Cal/d among women and 334 Cal/d among men, representing 8.9% of total daily calories (TDC). Women in the lowest SEL consumed 10.6% of their TDC from sugary drinks, as opposed to 6.6% for those in a high SEL. For men, this difference was not present (p-value for interaction = 0.039). Interestingly, a higher educational level correlated with a lower consumption of calories from sugary drinks only among men. Fruit juices were by far the main source of sugary drinks, and their consumption did not change sizably by sex and socioeconomic or educational level. Among women, there was a negative association between socioeconomic level (SEL) and consumption of regular soda, a 50% difference between extreme levels. The intake of low-calorie soda was much higher among men than women, and it more than tripled in the highest vs. lowest SEL among men. The consumption of energy drinks was heavily concentrated in men of low SEL. CONCLUSION: Colombian urban adults obtain a considerable proportion of their calories from sugary drinks, especially vulnerable groups such as women with lower education. Given the recent acceleration of the obesity epidemic in Latin America, strategies to limit the intake of such liquid calories may provide important public health benefits.

Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR ß/δ-dependent manner.

There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR ß/δ). J774A.1 murine macrophages were exposed to octanoate or decanoate as MCFA, a long-chain fatty acid control (palmitate), or the PPAR ß/δ agonist GW501516, with or without lipopolysaccharide (LPS) stimulation, and with or without an siRNA-induced knockdown of PPAR ß/δ. MCFA increased the expression of Plin2, encoding a lipid-droplet associated protein with anti-inflammatory effects in macrophages, in a partially PPAR ß/δ-dependent manner. Both MCFA stimulated expression of the cholesterol efflux pump ABCA1, more pronouncedly under LPS stimulation and in the absence of PPAR ß/δ. Octanoate stimulated the expression of Pltp, encoding a phospholipid transfer protein that aids ABCA1 in cellular lipid efflux. Only palmitate increased expression of the proinflammatory genes Il6, Tnf, Nos2 and Mmp9. Non-stimulated macrophages exposed to MCFA showed less internalization of fluorescently labeled lipoproteins. MCFA influenced the transcriptional responses of macrophages favoring cholesterol efflux and a less inflammatory response compared to palmitate. These effects were partially mediated by PPAR ß/δ.

MDRD is the eGFR equation most strongly associated with 4-year mortality among patients with diabetes in Colombia.

INTRODUCTION: We compared the association of glomerular filtration rate (GFR) estimated with the Cockcroft-Gault, Modification of Diet in Renal Disease study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or the new CKD-EPI without race (CKD-EPI-NR) equations, with 4-year all-cause mortality in patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed a nationwide, centralized database of all adults diagnosed with diabetes assisted by the Colombian Health System between July 1, 2015, and June 30, 2019. Plasma creatinine was used to calculate baseline estimated glomerular filtration rate (eGFR) and classify each patient in a chronic kidney disease (CKD) stage, by each of the four equations. We used multivariate logistic regression to compare the association between CKD stage and mortality, and receiver operating characteristic (ROC) analyses to assess the overall association of eGFR by each equation and mortality. RESULTS: The study included 758,219 patients (58% female, 7.2% black race, mean age 62.3, Glycated hemoglobin A1c [HbA1c] 7.4%). There were 35,296 deaths over the study follow-up. Considering eGFR by each equation as a continuous variable, the odds of death decreased by 1.1%-1.5% for each additional mL/min. Compared with CKD stage 1 of each equation, being placed in CKD stages 3a, 3b, or 4 by MDRD or CKD-EPI-NR was associated with greater odds of death than being categorized in the same stages by CKD-EPI. Among patients of black race, the adjusted OR of mortality for CKD stage 4 relative to stage 1 was 4.63 (95% CI 3.39 to 6.35) for MDRD, 3.66 (2.85 to 4.69) for CKD-EPI-NR, 3.01 (2.38 to 3.81) for CKD-EPI, and 2.82 (2.29 to 3.49) for Cockcroft-Gault. The area under the ROC curve to discriminate by survival status was greatest for MDRD, followed by CKD-EPI-NR, CKD-EPI, and Cockcroft-Gault, in that order (p<0.001 for all differences). CONCLUSIONS: Compared with other eGFR equations, MDRD showed the strongest association with all-cause mortality in a sample of Latin-American patients with diabetes. This difference was most pronounced among patients of black race.

Impact of metabolic control on all-cause mortality in a nationwide cohort of patients with diabetes from Colombia.

Objective: The magnitude of the mortality benefit conferred by good integral metabolic control in diabetes in not sufficiently known, especially among Latin American patients. We prospectively studied the association between sustained control of blood glucose (HbA1c<7%), systolic blood pressure (SBP) (<130 mmHg) and LDL (LDLc, <100mg/dL) and non-HDL (non-HDLc, <130 mg/dL) cholesterol, and death from any cause among all adult patients with diagnosed diabetes in Colombia. Methods: We retrospectively analyzed data from a nationwide, centralized, mandatory registry of all patients with diagnosed diabetes assisted by the Colombian health system between July 1, 2015, and June 30, 2019. We estimated the associations of sustained achievement of each goal, and of the joint triple goal (HbA1c + SBP + LDLc) with all-cause death. Associations were assessed after adjustment for sex, age, race, insurance type and BMI in multivariable logistic models. Results: We studied 1 352 846 people with diabetes. Sustained SBP (OR 0.42 [0.41-0.43]), HbA1c (OR 0.25 [0.24-0.26]) and LDLc (OR 0.28 [0.27-0.29]) control had strong negative associations with death. Moreover, among the 5.4% of participants who achieved joint, sustained metabolic control, the OR for death was 0.19 (0.18-0.21). Importantly, the impact of sustained, joint metabolic control was significantly smaller for patients of black race compared to other races (OR 0.31 [0.23-0.43] versus 0.18 [0.17-0.20], p-value for interaction <0.001), mostly at the expense of a smaller impact of LDLc control. The results were similar across body-mass index categories. Conclusions: Sustained and simultaneous metabolic control was associated with remarkably lower odds of death.

Strong Negative Association of non-HDL Cholesterol Goal Achievement With Incident CKD Among Adults With Diabetes.

Context: The relative importance of the control of different metabolic risk factors for the prevention of chronic kidney disease among patients with diabetes in real life conditions is insufficiently understood. Objective: We evaluated the effect of the achievement of glycated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDLc) or non-high-density lipoprotein cholesterol (non-HDLc) goals (ABC goals) on the development of incident chronic kidney disease (iCKD) among patients with diabetes. Methods: In a nationwide registry of all individuals diagnosed with diabetes assisted by the health system in Colombia, we analyzed the association between baseline or sustained goal achievement and development of iCKD over a 4-year follow-up. iCKD was defined as a new occurrence of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2, hemodialysis, peritoneal dialysis, or kidney transplant. Results: The study included 998 790 adults with diabetes (56% female, mean age 59). There were 125 626 cases of iCKD. After adjustment for multiple confounders, a baseline SBP less than 130 mm Hg (odds ratio [OR] 0.79 [0.78-0.80]) and a baseline HbA1c less than 7.0% (OR 0.86 [0.85-0.87]) were negatively associated with iCKD. Sustained achievement showed stronger negative associations with iCKD than just baseline achievement. Considering each goal separately, sustained non-HDLc less than 130 mg/dL had the strongest negative association with iCKD (OR 0.67 [0.65-0.69]). Patients who maintained the triple ABC goal over the entire follow-up had 32% (29-34) lower odds of developing CKD, 38% (34-42) if they additionally kept a normal body mass index (BMI). Sustained ABC control including a normal BMI was more strongly associated with a lower incidence of CKD in patients of Black race (OR 0.72 vs 0.89; P for interaction = .002). Conclusion: At the country level, sustained achievement of ABC goals and most especially non-HDLc were associated with substantial reductions in iCKD.

Low-density lipoproteins containing apolipoprotein C-III and the risk of coronary heart disease.

BACKGROUND: Low-density lipoprotein (LDL) that contains apolipoprotein (apo) C-III makes up only 10% to 20% of plasma LDL but has a markedly altered metabolism and proatherogenic effects on vascular cells. METHODS AND RESULTS: We examined the association between plasma LDL with apoC-III and coronary heart disease in 320 women and 419 men initially free of cardiovascular disease who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow-up and matched controls who remained free of coronary heart disease. Concentrations of LDL with apoC-III (measured as apoB in this fraction) were associated with risk of coronary heart disease in multivariable analysis that included the ratio of total cholesterol to high-density lipoprotein cholesterol, LDL cholesterol, apoB, triglycerides, or high-density lipoprotein cholesterol and other risk factors. In all models, the relative risks for the top versus bottom quintile of LDL with apoC-III were greater than those for LDL without apoC-III. When included in the same multivariable-adjusted model, the risk associated with LDL with apoC-III (relative risk for top versus bottom quintile, 2.38; 95% confidence interval, 1.54-3.68; P for trend <0.001) was significantly greater than that associated with LDL without apoC-III (relative risk for top versus bottom quintile, 1.25; 95% confidence interval, 0.76-2.05; P for trend=0.97; P for interaction <0.001). This divergence in association with coronary heart disease persisted even after adjustment for plasma triglycerides. CONCLUSIONS: The risk of coronary heart disease contributed by LDL appeared to result to a large extent from LDL that contains apoC-III.

Severe hypertriglyceridemia secondary to splice-site and missense variants in LMF1 in three patients from Ecuador.

Rare pathogenic variants in the LMF1 gene, which encodes lipase maturation factor 1, are a minor cause of familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia. In this report we present three adult patients, all of them born and raised in Quito, Ecuador, with severe hypertriglyceridemia secondary to biallelic LMF1 variants. In two of the three cases (patients 1 and 3), the presentation was acute pancreatitis secondary to plasma triglycerides well above 10 mmol/L. The other case (patient 2) was a sibling of one of the initial patients, who was asymptomatic but markedly hypertriglyceridemic. Next-generation sequencing revealed a homozygous splice-site variant in exon 6 of LMF1 in patients 1 and 2 (c.897G>A, p.Gln299=), and a homozygous missense variant in exon 2 of LMF1 in patient 3 (c.233T>C, p.Leu78Pro). The finding of two disease-causing variants in three patients from the same location raises the question of whether LMF1 may be a more prevalent cause of severe hypertriglyceridemia among Latin-American patients.

The Role of Angiopoietins in Neovascular Diabetes-Related Retinal Diseases.

Diabetic retinopathy is a devastating and frequent complication of poorly controlled diabetes, whose pathogenesis is still only partially understood. Advances in basic research over the last two decades have led to the discovery of angiopoietins, proteins that strongly influence the growth and integrity of blood vessels in many vascular beds, with particular importance in the retina. Angiopoietin 1 (Ang1), produced mostly by pericytes and platelets, and angiopoietin 2 (Ang2), produced mainly by endothelial cells, bind to the same receptor (Tie2), but exert opposing effects on target cells. Ang1 maintains the stability of the mature vasculature, while Ang2 promotes vessel wall destabilization and disruption of the connections between endothelial cells and pericytes. Human retinal endothelial cells exposed to Ang2 show reduced membrane expression of the adhesion molecule VE-cadherin, and patients with proliferative diabetic retinopathy or diabetic macular edema have markedly increased vitreal concentrations of Ang2. Faricimab, a bi-specific antibody simultaneously directed against Ang2 and VEGF, has shown promising results in clinical trials among patients with diabetic retinopathy, and other agents targeting the angiopoietin system are currently in development.

Achievement of treatment goals among adults with diabetes in Colombia, 2015-2019: Results from a national registry.

AIMS: To assess the achievement of essential treatment goals among patients with diabetes in Colombia. METHODS: We analyzed data from a nationwide registry of all individuals with diagnosed diabetes, hypertension or CKD assisted by the health system. We explored the prevalence of treatment goals (HbA1c < 7% [<53 mmol/mol], systolic blood pressure (SBP) < 130 mmHg and LDLc < 100 mg/dL), and their variations by race and type of health insurance, between July 1, 2015, and June 30, 2019. RESULTS: We studied 1 352 846 patients with diagnosed diabetes. The prevalence of HbA1c < 7% (<53 mmol/mol) remained steady at 52%, systolic blood pressure (SBP) < 130 mmHg was also stable at 80-82%. Meanwhile, the prevalence of both LDLc < 100 mg/dL and non-HDLc < 130 mg/dL increased by 6 percentage points. Achievement of the triple HbA1c + SBP + LDLc goal was only 21.4% in 2015, increasing to 24.4% by 2019. Goal achievement was consistently lower among patients of black race, especially for HbA1c (5% lower than other races), but also for the SBP, LDLc and joint goals. Patients under third-party insurance reached better HbA1c, SBP, and LDLc control. CONCLUSIONS: Achievement of treatment goals of patients with diabetes in Colombia remains substantially low, despite improvements in LDLc control.

Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins.

OBJECTIVE: We aimed to clarify the influence of apolipoprotein C-III (apoCIII) on human apolipoprotein B metabolism. METHODS AND RESULTS: We studied the kinetics of 4 very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) types containing: (1) otherApos-CIII-: none of apoCIII, apoAII, apoCI, apoCII, or apoE; (2) otherApos+CIII-: no apoCIII but at least one of the others; (3) otherApos-CIII+: apoCIII, but not any others; and (4) otherApos+CIII+: apoCIII and at least one other. VLDL and IDL otherApos-CIII+ and otherApos-CIII- had similar rates of lipolytic conversion to smaller particles. However, light LDL otherApos-CIII+ compared with otherApos-CIII- had much faster conversion to dense LDL as did light LDL otherApos+CIII+ compared with otherApos+CIII-. VLDL and IDL otherApos-CIII+ had minimal direct removal from circulation, whereas VLDL and IDL otherApos+CIII-, rich in apoE, showed fast clearance. Lipoproteins in fraction otherApos+CIII+ also rich in apoE had very low clearance. CONCLUSIONS: The results suggest that apoCIII strongly inhibits hepatic uptake of VLDL and IDL overriding the opposite influence of apoE when both are present. The presence of apoCIII on dense VLDL is not associated with slow conversion to IDL, a lipoprotein lipase-dependent process; but when on light LDL, apoCIII is associated with enhanced conversion to dense LDL, a process involving hepatic lipase.

Fish Consumption: A Review of Its Effects on Metabolic and Hormonal Health.

Dietary habits are a major determinant of the risk of chronic disease, particularly metabolic and endocrine disorders. Fish as a food group are a unique source of nutrients with metabolic and hormonal importance including omega-3 fatty acids, iodine, selenium, vitamin D, taurine and carnitine. Fish are also a source of high quality protein and have in general low caloric density. The impact of these nutrients on cardiovascular risk has been extensively reviewed, but the impact of fish on the broader field of endocrine and metabolic health is sometimes not sufficiently appreciated. This article aimed to summarize the impact the effect of regular fish consumption on conditions like the metabolic syndrome, obesity, diabetes, hypothyroidism, polycystic ovary syndrome and the menopausal transition, which are in and of themselves significant causes of morbidity and mortality worldwide. The review revealed that scientific evidence from food science, translational research, epidemiologic studies and interventional trials shows that regular fish consumption has a positive impact on thyroid homeostasis, facilitates maintenance of a healthy body weight, reduces the magnitude of age-associated increases in blood pressure, improves glucose homeostasis helping prevent diabetes and the metabolic syndrome, and has a positive impact on muscle mass preservation among the elderly. These effects are mediated by multiple mechanisms, only some of which have been identified. For most of these effects it holds true that the potential benefits are more substantial when baseline fish consumption is low.