RNA interference therapy in cardiology: will new targets improve therapeutic goals?

The discovery of RNA interference in 1998 opened avenues for the manipulation of gene expression, leading to the development of small interfering RNA (siRNA) drugs. Patisiran, the first FDA-approved siRNA medication, targets hereditary transthyretin amyloidosis with polyneuropathy. Givosiran, lumasiran and nedosiran further expand siRNA applications in treating rare genetic diseases, demonstrating positive outcomes. In cardiology, inclisiran, approved for hypercholesterolaemia, showcases sustained reductions in LDL cholesterol levels. However, ongoing research aims to establish its impact on cardiovascular outcomes. Lipoprotein(a), an independent risk factor for atherosclerotic cardiovascular disease, has become a focus of siRNA therapies, precipitating the development of specific siRNA drugs like olpasiran, zerlasiran and lepodisiran, with promising reductions in lipoprotein(a) levels. Research to assess the effectiveness of these medications in reducing events is currently under way. Zodasiran and plozasiran address potential risk factors for cardiovascular diseases, targeting triglyceride-rich lipoproteins. Zilebesiran, which targets hepatic angiotensinogen mRNA, has demonstrated a dose-related reduction in serum angiotensinogen levels, thereby lowering blood pressure in patients with systemic arterial hypertension. The evolving siRNA methodology presents a promising future in cardiology, with ongoing studies assessing its effectiveness in various conditions. In the future, larger studies will provide insights into improvements in cardiovascular outcomes, long-term safety and broader applications in the general population. This review highlights the historical timeline of the development of siRNA-based drugs, their clinical indications, potential side-effects and future perspectives.

Cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage I seminoma treated with a risk-adapted strategy: a Spanish single-centre retrospective analysis.

PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.

A systematic review and meta-analysis of serum lipid concentrations in people with Down syndrome.

BACKGROUND: Down syndrome (DS) is the most prevalent chromosomal disorder, being the leading cause of intellectual disability. The increased life expectancy of individuals with DS has led to a shift in the incidence of non-communicable chronic diseases, resulting in new concerns, particularly cardiovascular disease (CVD) and Alzheimer's disease. This study aimed to analyse the blood lipid profile of a large DS cohort to establish a baseline for evaluating health risk parameters. METHODS: A comprehensive literature search was conducted on PubMed and Virtual Health Library databases to identify original articles published before July 2022. Selected studies were included in the meta-analysis. RESULTS: Fifteen studies reporting serum lipid levels in individuals with DS were incorporated into the analysis. The meta-analysis used the means and standard deviations extracted from the selected studies. The analysis encompassed 671 participants in the DS group and 898 euploid controls. The results indicated significant differences in total cholesterol [C] (mean difference [MD]: -3.34; CI: 95%: -4.94 to -1.73; P < 0.0001), HDL-C (MD: -3.39; CI: 95%: -6.72 to -0.06; P = 0.05) and triglycerides (MD: 21.48; CI: 95%: 9.32 to 33.65; P = 0.0005) levels between individuals with DS and their control counterparts. CONCLUSIONS: Individuals with DS have less favourable blood lipid concentrations than their controls, particularly HDL-C, triglycerides, and total-C, even when grouped by age. These findings underscore the importance of closer monitoring of lipid profiles in people with DS and the necessity for specific cut-offs for this population, considering the risk for ischemic heart and Alzheimer's diseases.

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score.

Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity-related genetic risk score and atherogenic risk in Brazilian children. This is a cross-sectional study conducted in 544 children aged 4-9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity-related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi-structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual-Energy X-ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity-related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

Assessing statins use in a real-world primary care digital strategy: a cross-sectional analysis of a population-wide digital health approach.

Background: The digitization of the primary care system provides an opportunity to evaluate the current use of statins in secondary prevention populations (myocardial infarction or stroke). Methods: We conducted a cross-sectional study (ClinicalTrials.gov, NCT05285085), analysing anonymised data routinely collected by community health workers (CHW) in Brazil between May 2016 and September 2021 to assess the proportion of self-reported statins use and associated factors. Findings: From the 2,133,900 individuals on the database, 35,103 (1.6%), mean age 66.2 years (SD14.6), 49.5% (17,382/35,103) male sex, 50.5% (17,721/35,103) female sex, and 29.6% (10,381/34,975) Caucasians, had a previous myocardial infarction (MI) (n = 11,628; 33.1%) or stroke (n = 25,925; 73.9%). Approximately 50% (17,020/35,103) were from the Northeast region, 78.7% (27,605) from urban zones, and 39.4% (13,845) with social development index (SDI) >0.7. Overall, 6.7% (2346) and 0.6% (212) reported statins and high dose statins use, respectively. Age over 60 years old (OR 1.32 [95% CI 1.19-1.47), living in the Southern region (OR 4.53 [95% CI 3.66-5.60]), having a previous diagnosis of MI (OR 4.53 [95% CI 3.66-5.60]), heart failure (OR 2.29 [95% CI 1.13-1.47]), diabetes (OR 1.50 [95% CI 1.37-1.64]), dyslipidaemia (OR 2.90 [95% CI 2.55-3.29]), chronic kidney disease (OR 1.27 [95% CI 1.08-1.48]) and use of anti-hypertensives (OR 5.47 [95% CI 4.60-6.47]) were associated with statin use. Interpretation: The analysis of a real-world database from a digitized primary care system, allowed us to identify a very low use of statins in secondary prevention Brazilian patients, mostly influenced by socio-demographic factors and co-morbidities. Funding: Novartis Biociências, Brazil.

Early postnatal exposure of rat pups to methylglyoxal induces oxidative stress, inflammation and dysmetabolism at adulthood.

This work aimed to investigate the effects of early progeny exposure to methylglyoxal (MG), programming for metabolic dysfunction and diabetes-like complications later in life. At delivery (PN1), the animals were separated into two groups: control group (CO), treated with saline, and MG group, treated with MG (20 mg/kg of BW; i.p.) during the first 2 weeks of the lactation period. In vivo experiments and tissue collection were done at PN90. Early MG exposure decreased body weight, adipose tissue, liver and kidney weight at adulthood. On the other hand, MG group showed increased relative food intake, blood fructosamine, blood insulin and HOMA-IR, which is correlated with insulin resistance. Besides, MG-treated animals presented dyslipidaemia, increased oxidative stress and inflammation. Likewise, MG group showed steatosis and perivascular fibrosis in the liver, pancreatic islet hypertrophy, increased glomerular area and pericapsular fibrosis, but reduced capsular space. This study shows that early postnatal exposure to MG induces oxidative stress, inflammation and fibrosis markers in pancreas, liver and kidney, which are related to metabolic dysfunction features. Thus, nutritional disruptors during lactation period may be an important risk factor for metabolic alterations at adulthood.

Management of Dyslipidaemia in Real-world Clinical Practice: Rationale and Design of the VIPFARMA ISCP Project.

Dyslipidaemia plays a major role in the pathogenesis of atherosclerosis. Every year, scientific institutions publish cardiovascular prevention guidelines with updated goals and recommendations based on new evidence. However, medical barriers exist that make achieving these goals difficult and gaps between guidelines and best daily clinical practice still persist. The International Society of Cardiovascular Pharmacotherapy designed the Surveillance of Prescription Drugs in the Real World Project (VIPFARMA ISCP), a survey for physicians who manage lipid disorders in high-risk patients. Seven clusters of questions will be analysed comprising demographics, institution profile, access to continuing medical education, clinical practice profile, attitude regarding use of statins, knowledge regarding proprotein convertase subtilisin/kexin type 9 inhibitors and attitudes regarding medical decisions about triglycerides. The present study will be the first part of a larger programme and aims to shed light on barriers between lipid-lowering drug therapy recommendations in the 2019 European Society of Cardiology guidelines and clinical practice in different countries.

Modelling hypercholesterolaemia in rats using high cholesterol diet.

Hypercholesterolaemia is a complex condition with multiple causes, including both lifestyle and genetic aspects. It is also a risk factor for cardiovascular diseases (CVDs), which are responsible for 172 million deaths/year. Although the reasons for hypercholesterolaemia are known, there are many critical questions that remain to be answered so that new therapeutics can be developed. In order to elucidate the pathobiology of this condition, animal models can mimic the pathology of human hypercholesterolaemia. One example of an animal model is induced by the hypercholesterolaemic diet in Wistar rats. The present review first summarizes the current understanding of the metabolic profile involved in hypercholesterolaemia in humans. Next it comments about the lack of consensus as to which hypercholesterolaemia induction protocol should be used. The present work aimed to review experimental studies that induced hypercholesterolaemia in Wistar rats it was not intended to judge the "best" model, since they all achieved the goal of inducing an increase in serum cholesterol.

Skipping breakfast is associated with the presence of cardiometabolic risk factors in adolescents: Study of Cardiovascular Risks in Adolescents - ERICA.

Breakfast is considered as the most important meal of the day. The habit of skipping this meal in adolescence tends to remain until adulthood and has been associated with cardiometabolic risk factors. The present study estimated the prevalence of skipping breakfast and its association with cardiometabolic risk factors. This is a cross-sectional study with data from the Study of Cardiovascular Risks in Adolescents (ERICA), with a nationally representative sample of 36 956 Brazilian adolescents, aged 12-17 years, enrolled in public and private schools. The outcomes were excess body weight (BMI), central obesity (waist circumference and waist:height ratio), lipid profile (total cholesterol (TC), LDL-cholesterol, HDL-cholesterol and TAG) and glycidic profile (fasting glycaemia, fasting insulin and glycated Hb). The association between skipping breakfast and each outcome was estimated using multiple Poisson regression models (prevalence ratio (PR) and 95 % CI). Prevalence of skipping breakfast was 68·7 % and, after adjustments, it was associated with excess body weight (PR = 1·30; 95 % CI 1·18, 1·43), central obesity both by waist circumference (PR = 1·27; 95 % CI 1·00, 1·61) and by waist:height ratio (PR = 1·32; 95 % CI 1·13, 1·54) and high fasting glucose levels (PR = 1·54; 95 % CI 1·09, 2·18), fasting insulin (PR = 1·64; 95 % CI 1·21, 2·22), glycated Hb (PR = 1·16; 95 % CI 1·03, 1·31) and total cholesterol (PR = 1·14; 95 % CI 1·02, 1·27). Skipping breakfast was associated with cardiometabolic risk factors in adolescence. In this context, the school environment is an ideal space to promote healthy eating habits, favouring the implementation of food and nutrition education activities to make adolescents aware of the importance of consuming breakfast daily.

Dyslipidaemias and their treatment in high complexity centres in Colombia. / Las dislipidemias y su tratamiento en centros de alta complejidad en Colombia.

BACKGROUND AND OBJECTIVE: Data is scarce on the distribution of different types of dyslipidaemia in Colombia. The primary objective was to describe the frequency of dyslipidaemias. The secondary objectives were: frequency of cardiovascular comorbidity, statins and other lipid-lowering drugs use, frequency of statins intolerance, percentage of patients achieving c-LDL goals, and distribution of cardiovascular risk (CVR). MATERIALS AND METHODS: Cross-sectional study with retrospective data collection from 461 patients diagnosed with dyslipidaemia and treated in 17 highly specialised centres distributed into six geographic and economic regions of Colombia. RESULTS: Mean (SD) age was 66.4 (±12.3) years and 53.4% (246) were women. Dyslipidaemias were distributed as follows in order of frequency: mixed dyslipidaemia (51.4%), hypercholesterolaemia (41.0%), hypertriglyceridaemia (5.4%), familial hypercholesterolaemia (3.3%), and low c-HDL (0.7%). The most prescribed drugs were atorvastatin (75.7%) followed by rosuvastatin (24.9%). As for lipid control, 55% of all patients, and 28.6% of those with coronary heart disease, did not achieve their personal c-LDL goal despite treatment. The frequency of statin intolerance was 2.6% in this study. CONCLUSIONS: Mixed dyslipidaemia and hypercholesterolaemia are the most frequent dyslipidaemias in Colombia. A notable percentage of patients under treatment with lipid-lowering drugs, including those with coronary heart disease, did not achieve specific c-LDL goals. This poor lipid control may worsen patient's CVR, so that therapeutic strategies need to be changed, either with statin intensification or addition of new drugs in patients with higher CVR.

A Narrative Review and Expert Panel Recommendations on Dyslipidaemia Management After Acute Coronary Syndrome in Countries Outside Western Europe and North America.

Patients who have experienced an acute coronary syndrome (ACS) are at very high risk of recurrent atherosclerotic cardiovascular disease (CVD) events. Dyslipidaemia, a major risk factor for CVD, is poorly controlled post ACS in countries outside Western Europe and North America, despite the availability of effective lipid-modifying therapies (LMTs) and guidelines governing their use. Recent guideline updates recommend that low-density lipoprotein cholesterol (LDL-C), the primary target for dyslipidaemia therapy, be reduced by ≥ 50% and to < 1.4 mmol/L (55 mg/dL) in patients at very high risk of CVD, including those with ACS. The high prevalence of CVD risk factors in some regions outside Western Europe and North America confers a higher risk of CVD on patients in these countries. ACS onset is often earlier in these patients, and they may be more challenging to treat. Other barriers to effective dyslipidaemia control include low awareness of the value of intensive lipid lowering in patients with ACS, physician non-adherence to guideline recommendations, and lack of efficacy of currently used LMTs. Lack of appropriate pathways to guide follow-up of patients with ACS post discharge and poor access to intensive medications are important factors limiting dyslipidaemia therapy in many countries. Opportunities exist to improve attainment of LDL-C targets by the use of country-specific treatment algorithms to promote adherence to guideline recommendations, medical education and greater prioritisation by healthcare systems of dyslipidaemia management in very high risk patients.

Multimodal HIIT is more efficient than moderate continuous training for management of body composition, lipid profile and glucose metabolism in the diabetic elderly / El entrenamiento multimodal es más eficiente que el entrenamiento continuo moderado para el manejo de la composición corporal, el perfil de lípidos y el metabolismo de la glucosa en adultos mayores diabéticos

The exercise could play a central role to the fat management and glucose metabolism what can be a critical role in the health status of diabetic people, but the high intense exercise remains with controversial data about their effects. To identify the effect of the multimodal high-intensity interval training on body composition, lipid profile, and glucose metabolism in elderly diabetics. Methods: Elderly diabetic individuals (n = 48) were randomly divided in a Sedentary Control (SC) group, a Moderate-Intensity Continuous Training (MICT) group, and a High-Intensity Interval Training (HIIT) group. MICT and HITT were conducted over 60 days, 3x per week, with 40 minutes of exercise. Blood was collected prior to intervention, at four, and at eight weeks subsequently to assess glucose metabolism and lipid profiles. Body composition was determined before and after the intervention period. To verify the normality Kolmogorov-Smirnov statistical test was performed, followed by student "t" test or two-way ANOVA with Bonferroni's post hoc test with significance of 5 % the Cohen's f test to indicate the magnitude of the differences. HIIT significantly lowered cholesterol and triglyceride levels, and significantly lowered blood glucose and glycosylated haemoglobin levels (p<0.05). MICT and HIIT significantly increased levels of high-density lipoprotein, decreased total body mass and body mass index. HIIT resulted in significantly smaller waist circumferences, waist-to-hip ratios, and weight-to-height ratios over 60 days of training. HIIT is more effective than MICT for improving lipid and glycaemic profiles, decreasing body fat, and improving fat distribution elderly diabetics.

El ejercicio podría desempeñar un papel central en el manejo de la grasa y el metabolismo de la glucosa, lo que puede ser un papel crítico en el estado de salud de las personas diabéticas, pero el ejercicio intenso intenso sigue teniendo datos controvertidos sobre sus efectos. El objetivo del estudio fue identificar el efecto del entrenamiento multimodal de intervalos de alta intensidad sobre la composición corporal, el perfil lipídico y el metabolismo de la glucosa en diabéticos de edad avanzada. Los individuos diabéticos de edad avanzada (n = 48) se dividieron aleatoriamente en un grupo de control sedentario (SC), un grupo de entrenamiento continuo de intensidad moderada (MICT) y un grupo de entrenamiento de intervalos de alta intensidad (HIIT). MICT y HITT se realizaron durante 60 días, 3 veces por semana, con 40 minutos de ejercicio. Se recogió sangre antes de la intervención, a las cuatro y a las ocho semanas posteriormente para evaluar el metabolismo de la glucosa y los perfiles de lípidos. La composición corporal se determinó antes y después del período de intervención. Para verificar la normalidad se realizó la prueba estadística de Kolmogorov-Smirnov, seguida de la prueba "t" de Student o ANOVA de dos vías con la prueba post hoc de Bonferroni con una significancia del 5 % de la prueba f de Cohen, indicando las diferencias. HIIT redujo significativamente los niveles de colesterol y triglicéridos, además de reducir de manera importante los niveles de glucosa en la sangre y la hemoglobina glicosilada (p <0.05). MICT y HIIT aumentaron significativamente los niveles de lipoproteína de alta densidad, disminuyeron la masa corporal total y el índice de masa corporal. HIIT resultó en circunferencias de cintura significativamente más pequeñas, relaciones cintura-cadera y relaciones peso-altura durante 60 días de entrenamiento. HIIT es más efectivo que MICT para mejorar los perfiles de lípidos y glucémicos, disminuir la grasa corporal y mejorar la distribución de grasa en los diabéticos de edad avanzada.

New Perspectives on Atherogenic Dyslipidaemia and Cardiovascular Disease.

Over the past few decades, atherogenic dyslipidaemia has become one of the most common phenotypic presentations of lipid abnormalities, being strongly and unequivocally associated with an increased risk of cardiovascular (CV) disease. Despite the excellent results achieved from statin and non-statin management of LDL cholesterol and CV events prevention, there still remains a significant residual risk, associated with the prevalence of non-LDL cholesterol lipid patterns characterised by elevated triglyceride levels, low HDL cholesterol, a preponderance of small and dense LDL particles, accumulation of remnant lipoproteins and postprandial hyperlipidaemia. These qualitative and quantitative lipid modifications are largely associated with insulin resistance, type 2 diabetes and obesity, the prevalence of which has grown to epidemic proportions throughout the world. In this review, we analyse the pathophysiology of this particular dyslipidaemia, its relationship with the development of atherosclerotic CV disease and, finally, briefly describe the therapeutic approaches, including changes in lifestyle and current pharmacological interventions to manage these lipid alterations aimed at preventing CV events.

Short- and long-term effects of maternal dyslipidaemia on blood pressure and baroreflex sensitivity in male rat offspring.

Maternal dyslipidaemia is a predisposing factor for arterial hypertension in male rat offspring at adulthood. This study was designed to investigate the short- and long-term effects of maternal dyslipidaemia on blood pressure (BP) and baroreflex control in male rat offspring. Animals were obtained from mothers who received a dyslipidaemic (DLP, n = 7) or control (CTL, n = 7) diet during pregnancy and lactation. At 30 and 90 days of age, arterial pressure (AP), heart rate (HR) and baroreflex function were evaluated. In addition, spectral analysis of the systolic AP, diastolic AP, mean AP, HR, and spontaneous baroreflex were assessed. Data were expressed as mean ± SEM and Student's t-test was used for comparison among groups, with statistical significance considered to be P < .05. At 30 days of age, male offspring had similar BP, HR and preserved baroreflex sensitivity. In addition, low frequency (LF) oscillation, high frequency (HF) oscillation and LF/HF ratio of AP and HR were similar in juvenile rats. At 90 days of age, male offspring from dyslipidaemic dams had augmented BP (P < .05) when compared to CTL group. Adult male rats from dyslipidaemic dams had a reduction in baroreflex control (P < .05) in comparison to CTL rats. The present study indicates that offspring from dams fed on a dyslipidaemic diet during pregnancy and lactation do not show alteration in blood pressure and baroreflex control in early life, but display a decline in baroreflex control and hypertension in adulthood.

Widespread use of anti-retroviral therapy elevated the prevalence of dyslipidemia in HIV-infected Chinese patients

With the widespread use of high-efficiency antiretroviral therapy (HAART), the life expectancy of HIV-infected patients has been significantly extended. However, the metabolic complications among HIV-infected patients treated with HAART have become the most common problem in the world. It is very important to explore the incidence of dyslipidaemia and studies on the role of potential risk factors in HIV-infected Chinese patients treated with HAART are sparse. Therefore, we designed current study, to investigate the effects of therapeutic intervention and continuous information support on the lifestyle of HIV/AIDS patients with dyslipidaemia. Three hundred and six HIV/AIDS patients admitted to the AIDS clinic in Beijing from January 2016 to January 2017 were recruited and assigned into two groups: the treatment group (n=64) and the control group (n=64). The median age of the participants was 38.8±11.0 years (range 20-75 years). The prevalence of dyslipidemia in control and treatment group was (59/64) 92.2% and (53/64) 82.8%, respectively. In this study, low HDL-cholesterol (HDLC) led to abnormalities 47/64 (73.3%) in the control group and 35/64 (54.7%) in HAART-treatment group. Additionally, HAART group showed higher triglyceride, total cholesterol, and low-density lipoprotein (246.1±171.8, 1.73±1.61 mmol/L, 4.46±1.1 mmol/L, 2.54±0.74 mmol/L). In multivariate analysis, gender, marital status, high BMI, dietary habits and physical activity were potential risk factors for dyslipidemia in HIV-infected Chinese patients. In this study, we reported high prevalence dyslipidemiain two HIV infected groups. We suggest that the appropriate diagnosis should be performed for analyzing the metabolic complications in HIV-infected Chinese patients. Further studies are very important to understand the role of potential risk factors in metabolic complications.

Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Primary results of the BERSON clinical trial.

AIM: To evaluate the lipid-lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia. MATERIALS AND METHODS: BERSON was a double-blind, 12-week, phase 3 study (NCT02662569) conducted in 10 countries. Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were randomised 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Co-primary endpoints were the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures, and adverse events (AEs). RESULTS: Overall, 981 patients were randomised and received ≥1 dose of study drug. Evolocumab significantly reduced LDL-C versus placebo at week 12 (Q2W, -71.8%; QM, -74.9%) and at the mean of weeks 10 and 12 (Q2W, -70.3%; QM, -70.0%; adjusted P < 0.0001 for all) when administered with atorvastatin. Non-high-density lipoprotein cholesterol, apolipoprotein B100, total cholesterol, lipoprotein (a), triglycerides, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol improved significantly with evolocumab versus placebo. The overall incidence of AEs was similar between evolocumab and placebo-treated patients, and there were no clinically meaningful differences in changes over time in glycaemic variables (fasting serum glucose and HbA1c) between the two groups. CONCLUSIONS: In patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Maternal Dyslipidaemia in Pregnancy with Gestational Diabetes Mellitus: Possible Impact on Foetoplacental Vascular Function and Lipoproteins in the Neonatal Circulation.

Dyslipidaemia occurs in pregnancy to secure foetal development. The mother shows a physiological increase in plasma total cholesterol and Triglycerides (TG) as pregnancy progresses (i.e. maternal physiological dyslipidaemia in pregnancy). However, in some women pregnancy-associated dyslipidaemia exceeds this physiological adaptation. The consequences of this condition on the developing fetus include endothelial dysfunction of the foetoplacental vasculature and development of foetal aortic atherosclerosis. Gestational Diabetes Mellitus (GDM) associates with abnormal function of the foetoplacental vasculature due to foetal hyperglycaemia and hyperinsulinaemia, and associates with development of cardiovascular disease in adulthood. Supraphysiological dyslipidaemia is also detected in GDM pregnancies. Although there are several studies showing the alteration in the maternal and neonatal lipid profile in GDM pregnancies, there are no studies addressing the effect of dyslipidaemia in the maternal and foetal vasculature. The literature reviewed suggests that dyslipidaemia in GDM pregnancy should be an additional factor contributing to worsen GDM-associated endothelial dysfunction by altering signalling pathways involving nitric oxide bioavailability and neonatal lipoproteins.

Association of hypertension and dyslipidaemia with increasing obesity in patients with Type 2 Diabetes Mellitus

The study was performed to estimate the association of hypertension and dyslipidaemia with increasing body weight and obesity in Type II diabetics of Lahore, Pakistan. An observational study was conducted by enrolling 2708 obese diabetics from four diabetes care centres of Lahore, Pakistan. Data was collected for a period of 7 months. Associations were estimated using chi-square, binary and multinomial logistic regression. Data suggested that blood pressure, systolic and diastolic, exhibited continual increase with increasing body weight and obesity class in diabetes patients with 41.8% increase in the prevalence of hypertension in obesity class III subjects (OR; 1.91, p=0.02). Likewise, triglycerides and total cholesterol exhibited continual increase in their mean values with increasing obesity, i-e., an overall increase in the prevalence of dyslipidaemia of 27.2% in obesity class 3 subjects (OR; 1.94, p=0.29). Taken together, this data suggested that hypertension is potentially associated with increasing obesity in diabetics, while dyslipidaemia demonstrated plausible association only with obesity class 3.

Metformin reduces insulin resistance and the tendency toward hyperglycaemia and dyslipidaemia in dogs with hyperadrenocorticism.

Hypercortisolism induces a state of insulin resistance that can occur concurrently with fasting hyperglycaemia, dyslipidaemia and diabetes mellitus. Metformin reduces hepatic glucose production and insulin resistance of the skeletal muscle and adipose tissue. The aim of this study was to evaluate the effects of metformin on the control of metabolic disorders of dogs with hyperadrenocorticism (HAC). Twenty-three dogs with HAC were randomly divided into two groups, consisting of a control group and a metformin group (10 mg metformin/kg/12 h). Both groups received the same treatment for HAC. At baseline and 3 months, blood glucose, total cholesterol, triglycerides and insulin concentrations, in addition to urinary cortisol:creatinine ratio, Homeostatic Model Assessment (HOMA) for insulin sensitivity and ß-cell function were measured. Dogs treated with metformin showed significantly reduced glycaemia, cholesterolaemia and triglyceridaemia. They also presented reduced hyperinsulinism and insulin resistance, as well as improved pancreatic ß-cell function. The implementation of metformin as an adjuvant therapy is effective for the normalisation of metabolic disorders of dogs with HAC.

Lower vitamin D intake is associated with low HDL cholesterol and vitamin D insufficiency/deficiency in Brazilian children.

OBJECTIVE: To evaluate the association of vitamin D intake with dyslipidaemia and vitamin D insufficiency/deficiency in Brazilian children and identify the main food group sources of this nutrient in the sample. DESIGN: A cross-sectional study carried out with a representative sample. Blood was collected after 12 h of fasting. Laboratory tests were performed to determine total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol, TAG, apoB, apoA1, 25-hydroxyvitamin D and parathyroid hormone. Dietary intake was evaluated by a 24 h recall. SETTING: Viçosa, Minas Gerais, Brazil. SUBJECTS: Children between 8 and 9 years old enrolled in urban schools (n 378). RESULTS: We found an elevated prevalence of inadequate vitamin D intake (91·3 %), dyslipidaemia (72·8 %) and vitamin D insufficiency/deficiency (56·2 %). The food groups that contributed the most to vitamin D intake were dairy products and fish. Lower vitamin D intake was associated with increased prevalence of both low HDL-C (prevalence ratio=2·51; 95 % CI 1·02, 6·18; P<0·05) and vitamin D insufficiency/deficiency (prevalence ratio=1·61; 95 % CI 1·01, 2·58; P<0·05). CONCLUSIONS: Given the elevated prevalence of inadequate vitamin D intake and its association with low HDL-C and vitamin D insufficiency/deficiency, it is important to develop specific actions in food and nutritional education as well as programmes that stimulate and facilitate access to vitamin D food sources, such as dairy products and fish.