Primary Dyslipidemia Research Articles

Lipoprotein X in Cholestasis and Questionable Atherogenic Risk

Lipoprotein X is still an enigma for its lack of evidence as a risk association with atherosclerosis. Primary biliary cirrhosis is a chronic, autoimmune cholestatic liver disease characterized by the presence of T cells that destroy the biliary epithelium. In patients with primary biliary cirrhosis, total cholesterol levels may reach values between 500 and 1000 mg/dL, with cutaneous xanthomas similar to those observed in genetic hypercholesterolemias. The rise in cholesterol is largely due to increased serum levels of lipoprotein-X. It has a small amount of albumin, apoprotein AI, apoprotein Cs and apoprotein E and has no apoprotein B. The formation of lipoprotein-X results from regurgitation of bile lipids in plasma, as well as the accumulation of plasma phospholipids and free cholesterol, resulting from the lower activity of lecithin: acyltransferase cholesterol. Multicenter randomized trials are needed to assess the impact of lipid-lowering patients on lipid reduction and cardiovascular risk, as well as the effect on hepatic cholestasis. Treatment with statins is not indicated for lowering cholesterol in patients with primary biliary cirrhosis and dyslipidemia, as there is no evidence that these patients have high cardiovascular risk.

High prevalence of plasma lipid abnormalities in human and canine Duchenne and Becker muscular dystrophies depicts a new type of primary genetic dyslipidemia

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive muscle diseases caused by mutations in the DMD gene, with DMD being the more severe form. We have recently shown that increased plasma low-density lipoprotein-associated cholesterol causes severe muscle wasting in the mdx mouse, a mild DMD model, which suggested that plasma lipids may play a critical role in DMD. We have also observed that loss of dystrophin in mice causes unexpected elevations in plasma lipoprotein levels. The objectives of the study were to determine whether patients with DMD and BMD also present with clinically relevant plasma lipoprotein abnormalities and to mitigate the presence of confounders (medications and lifestyle) by analyzing the plasma from patients with DMD/BMD and unmedicated dogs with DMD, the most relevant model of DMD. Levels of low-density lipoprotein-associated cholesterol, high-density lipoprotein cholesterol, and triglycerides were analyzed in patients with DMD and BMD and female carriers. Samples from unmedicated, ambulatory dogs with DMD, unaffected carriers, and normal controls were also analyzed. We report that 97% and 64% of all pediatric patients with DMD (33 of 36) and BMD (6 of 11) are dyslipidemic, along with an unusually high incidence in adult patients with BMD. All dogs with DMD showed plasma lipid abnormalities that progressively worsened with age. Most strikingly, unaffected carrier dogs also showed plasma lipid abnormalities similar to affected dogs with DMD. Dyslipidemia is likely not secondary to liver damage as unaffected carriers showed no plasma aminotransferase elevation. The high incidence of plasma lipid abnormalities in dystrophin-deficient plasma may depict a new type of genetic dyslipidemia. Abnormal lipid levels in dystrophinopathic samples in the absence of muscle damage suggest a primary state of dyslipidemia. Whether dyslipidemia plays a causal role in patients with DMD warrants further investigation, which could lead to new diagnostic and therapeutic options.

Statin adherence and LDL-C reduction in a pediatric population

Statins have demonstrated efficacy and safety in children with primary dyslipidemias such as familial hypercholesterolemia; however, adherence plays a key role in the ability of a statin to lower low-density lipoprotein cholesterol (LDL-C) levels. The objective of this study was to examine the role medication adherence plays in statin efficacy for the treatment of primary and secondary pediatric dyslipidemias. Retrospective review of a pediatric preventive cardiology database identified all subjects <22 years old who were prescribed a statin. Dosing, adverse effects, pre- and on-treatment LDL-C levels, medication adherence, and family history of atherosclerotic cardiovascular disease (ASCVD) were recorded. Adherence to medication was considered adequate if subject self-reported taking ≥80% of prescribed doses in the 14 days prior to lowest treatment LDL-C value. Chart review identified 131 subjects aged 6–21 years prescribed a statin with pre- and on-treatment data available. Of these 131 subjects, 123 (94%) had LDL-C > 130 mg/dL before beginning a statin. On treatment, 100/131 subjects (76%) met the LDL-C target of ≤130 mg/dL. Of 83 subjects with adherence data available, 61 (73%) met the adherence threshold and the adherent group had significantly greater mean reduction in LDL-C compared to the non-adherent group (−91 mg/dL versus −20 mg/dL, p = .0001). There were no reported adverse effects. These findings indicate that reductions in LDL-C were dependent on medication adherence. Utilizing a model of early intervention, family education, and intensive follow-up to improve adherence may improve clinical outcomes and reduce future ASCVD events in children with primary and secondary dyslipidemias that require lipid-lowering therapy.

Impact of Obesity on Castelli’s Risk Index I and II, in Young Adult Females

Background: Obesity is one of today’s most blatantly visible, yet most neglected, public health problems. In 2016, 39% of adults worldwide were overweight. Fueled by economic growth, urbanization, an increasingly sedentary lifestyle, and a nutritional transition to processed foods and high calorie diets over the last 30 years, many countries have witnessed the prevalence of obesity in its citizens double, and even quadruple. Obesity especially visceral obesity causes insulin resistance and is associated with dyslipidemia, impaired glucose metabolism, and hypertension all of which exacerbate atherosclerosis, and are risk factors for developing cardiovascular diseases (CVD). The primary dyslipidemia related to obesity is characterized by increased total cholesterol (TC), decreased high density lipoprotein (HDL) levels and abnormal low density lipoprotein (LDL) composition. Lipoprotein ratios are becoming increasingly popular as a way to predict atherosclerosis and CVD. Aims and Objectives: The present study was undertaken to assess the impact of overweight/obesity on lipid profile parameters and lipoprotein ratios- Castelli’s Risk Index I and II, in young adult females. Materials and Method: The present study was conducted in KIMS, Hubli, the study and its conduct was cleared by the Ethical committee. Sixty apparently healthy young females were selected for the study. Health status and other personal data were obtained via comprehensive questionnaire. The subjects were divided into two groups based on BMI; Healthy (BMI 18.5-24.99) and Overweight (BMI > 25). Lipid profile was evaluated and lipoprotein ratios calculated. Comparison between the two groups was done using students’ t-test. Results: Values for Castelli’s Risk Index I & II were found to be significantly higher in the overweight group compared to the control group. Conclusion: Obesity leads to an unfavorable lipid pattern and raises values of both Castelli’s Risk Index I & II.

Bempedoic acid: effect of ATP-citrate lyase inhibition on low-density lipoprotein cholesterol and other lipids.

Bempedoic acid is a new, first-in-class oral ATP-citrate lyase (ACLY) inhibitor that has to be converted to its CoA thioester before it inhibits ACLY. This conversion only occurs in the liver and not in skeletal muscle. This may explain why, unlike the statins, bempedoic acid does not cause myalgia. Bempedoic acid given at a dosage of 180 mg orally once daily produces a highly significant reduction in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and importantly also in high-sensitivity C-reactive protein. It has recently been approved by both the Food and Drug Administration (FDA) and the European Commission for use in adult patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional lowering of LDL-C, and for the treatment of adults with primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia, respectively.

Efficacy and Tolerability of a Fixed-Dose Combination of Rosuvastatin and Ezetimibe Compared with a Fixed-Dose Combination of Simvastatin and Ezetimibe in Brazilian Patients with Primary Hypercholesterolemia or Mixed Dyslipidemia: A Multicenter, Randomized Trial

Background: The addition of ezetimibe to statin therapy has been reported to result in increased efficacy for reduction of LDL-C levels and achievement of lipid targets, compared with monotherapy.Objective: This study was designed to demonstrate the noninferiority of therapy with fixed-dose rosuvastatin plus ezetimibe formulations versus fixed dose simvastatin and ezetimibe formulations for reduction of LDL-C levels in Brazilian patients with hypercholesterolemia or mixed dyslipidemia.Methods: Phase III, multicenter, randomized, parallel, open-label, noninferiority study that included male and female participants (aged 21–80 years) with hypercholesterolemia or mixed dyslipidemia. After a 1-week screening period with washout of lipid-lowering medications when needed, patients were treated with simvastatin 20 mg/d for 5 weeks. Participants with LDL-C levels ≥100 mg/dL after the initial treatment were submitted to a 1-week washout period, and then randomized 1:1 to receive either combined rosuvastatin 10 mg + ezetimibe 10 mg (R/E) or simvastatin 20 mg + ezetimibe 10 mg (S/E) for 4 weeks and, if they still did not achieve the stipulated target, doses were readjusted to rosuvastatin 20 mg + ezetimibe 10 mg or simvastatin 40 mg + ezetimibe 10 mg, respectively, for 4 weeks.Results: One hundred twenty-nine participants were enrolled, including 66 in R/E and 63 in S/E. At the end of simvastatin 20 mg treatment period, mean LDL-C values were 124.79 mg/dL and 121.27 mg/dL for participants randomized to R/E and S/E arms, respectively. After 4 weeks of R/E 10 mg + 10 mg or S/E 20 mg + 10 mg combined treatments, adjusted mean LDL-C values were 74.21 mg/dL and 85.58 mg/dL, respectively (P = 0.0005), and after 9 weeks, with dose adjustment to R/E 20 mg + 10 mg in 6 patients and to S/E 40 mg +10 mg in 19 patients, LDL-C adjusted mean values were 75.29 mg/dL and 86.62 mg/dL, respectively (P = 0.0006). There was a statistically significant difference between the association R/E and S/E (P = 0.0013) in percentage change of LDL-C after 9 weeks of combined treatments. The adjusted mean difference was estimated at –10.32% (95% CI, –16.94% to –3.70%). The LDL-C <100 mg/dL target was achieved in a significantly greater proportion of participants at week 4 in the R/E compared with the S/E arm (84.8% vs 68.2%; P = .0257), and at week 9, the proportion was 81.2% versus 73.0%, respectively (P = 0.23). LDL­C <70 mg/dL was achieved at a significantly greater proportion in the R/E arm, both at week 4 (45.4% vs 15.9%; P = 0.003) and week 9 (40.9% vs 15.9%; P = 0.0017). A statistically significant difference at week 9 (P = 0.0106) was observed in fasting blood glucose in the R/E arm, but the overall incidence of adverse events was not significantly different between groups.Conclusions: Rosuvastatin and ezetimibe fixed dose combination in both 10 mg/10 mg and 20 mg/10 mg doses, respectively, provided significantly lower levels of LDL-C compared with simvastatin and ezetimibe in doses of 20 mg/10 mg and 40 mg/10 mg, respectively. The fixed-dose combinations were both effective and well tolerated in this Brazilian study population. ClinicalTrials.gov identifier: NCT01420549. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)

SAT-085 Severe Dyslipidemia Secondary to Autoimmune Hypothyroidism: A Case Report

Background: Up to 28% of patients have an underlying potential secondary cause for dyslipidemia. Frequently, the treatment of the underlying cause can lead to normalization of lipid profile. Case report: A 34-year-old male presented with a 12-months history of asthenia, facial swelling, cold intolerance, sleepiness, poor concentration, but stable weight. Physical examination highlighted bilateral palpebral edema. His past medical history was significant for mixed dyslipidemia at least for 2 years (total cholesterol [TC] 326 mg/dL, high-density lipoprotein cholesterol [HDL-C] 84 mg/dL, low-density lipoprotein cholesterol [LDL-C] 199 mg/dL and triglycerides [TG] 211 mg/dL), but no secondary causes of dyslipidemia were excluded, namely hypothyroidism, neither treatment was instituted. He also had overweight (body mass index [BMI] of 29 kg/m2) and hepatic steatosis. There was no familial history of dyslipidemia. Laboratory assessment revealed TC 426 mg/dL, HDL-C 89 mg/dL, LDL-C 293.6 mg/dL, TG 217 mg/dL, thyroid-stimulating hormone (TSH) > 100 μUI/mL (reference: 0.550-4.780), free thyroxine (FT4) < 0.3 ng/dL (reference: 0.70-1.58), free triiodothyronine (FT3) < 0.195 pg/mL (reference: 1.71-3.71), positive thyroglobulin antibody and negative peroxidase antibody. Thyroid ultrasonography showed a normal size gland, with heterogeneous texture and pseudonodular areas, without nodular lesions, suggesting thyroiditis. Given the diagnosis of primary autoimmune overt hypothyroidism and mixed dyslipidemia, the patient was given oral levothyroxine up to 137 μg/day and atorvastatin 10 mg/day. After normalization of thyroid function by treatment with levothyroxine, there was an important improvement in overall well-being and in the lipid profile (TC 184 mg/dL, HDL-C 46 mg/dL, LDL-C 115 mg/dL, TG 113 mg/dL), leading to statin withdrawal. Conclusion: This case highlighted a severe dyslipidemia secondary to overt autoimmune hypothyroidism in a young male. The delayed diagnosis of hypothyroidism could have been avoided if a secondary cause for dyslipidemia was initially suspected. Secondary causes of dyslipidemia, namely hypothyroidism, should be considered and excluded in any young patient with no or few risk factors.

Characteristics of Children Referred to a Lipid Clinic Before and After the Universal Screening Guidelines.

In 2011, universal lipid screening was recommended for children aged 9 to 11 years; the impact of this recommendation on the lipid clinic setting is unknown. We examined the rate of primary and secondary dyslipidemia diagnoses in a lipid clinic before (2010-2011) and after (2012-2015) the guideline recommendation. We conducted a retrospective study of new clinic patients aged 0 to 20 years seen between April 2010 and April 2015. Chi-square testing was applied. The 345 subjects were 58% males; 48% ≥13 years; 56% Hispanic; and 59% obese. There was no difference in the rate of dyslipidemia diagnoses between periods (before: primary 23%, secondary 73%, no dyslipidemia 4% vs after: 22%, 72%, 6%, respectively; P = .616). There was no significant difference between periods in subject demographics for the total sample, but among those with primary dyslipidemia, pre- to post-guideline percentage of subjects with public insurance decreased (71% to 39%; P = .006). Additional strategies to increase identification of children with dyslipidemia are needed.

Normal serum ApoB48 and red cells vitamin E concentrations after supplementation in a novel compound heterozygous case of abetalipoproteinemia

Background and aimsAbetalipoproteinemia (ABL) is a rare recessive monogenic disease due to MTTP (microsomal triglyceride transfer protein) mutations leading to the absence of plasma apoB-containing lipoproteins. Here we characterize a new ABL case with usual clinical phenotype, hypocholesterolemia, hypotriglyceridemia but normal serum apolipoprotein B48 (apoB48) and red blood cell vitamin E concentrations. MethodsHistology and MTP activity measurements were performed on intestinal biopsies. Mutations in MTTP were identified by Sanger sequencing, quantitative digital droplet and long-range PCR. Functional consequences of the variants were studied in vitro using a minigene splicing assay, measurement of MTP activity and apoB48 secretion. ResultsIntestinal steatosis and the absence of measurable lipid transfer activity in intestinal protein extract supported the diagnosis of ABL. A novel MTTP c.1868G>T variant inherited from the patient's father was identified. This variant gives rise to three mRNA transcripts: one normally spliced, found at a low frequency in intestinal biopsy, carrying the p.(Arg623Leu) missense variant, producing in vitro 65% of normal MTP activity and apoB48 secretion, and two abnormally spliced transcripts resulting in a non-functional MTP protein. Digital droplet PCR and long-range sequencing revealed a previously described c.1067+1217_1141del allele inherited from the mother, removing exon 10. Thus, the patient is compound heterozygous for two dysfunctional MTTP alleles. The p.(Arg623Leu) variant may maintain residual secretion of apoB48. ConclusionsComplex cases of primary dyslipidemia require the use of a cascade of different methodologies to establish the diagnosis in patients with non-classical biological phenotypes and provide better knowledge on the regulation of lipid metabolism.

FAMILIAL COMBINED HYPERLIPIDEMIA: CURRENT KNOWLEDGE, PERSPECTIVES, AND CONTROVERSIES.

Familial combined hyperlipidemia (FCHL) is the most prevalent primary dyslipidemia; however, it frequently remains undiagnosed and its precise definition is a subject of controversy. FCHL is characterized by fluctuations in serum lipid concentrations and may present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B. FCHL is an oligogenic primary lipid disorder, which can occur due to the interaction of several contributing variants and mutations along with environmental triggers. Controversies surrounding the relevance of identifying FCHL as a cause of isolated hypertriglyceridemia and a differential diagnosis of familial hypertriglyceridemia are offset by the description of associations with USF1 and other genetic traits that are unique for FCHL and that are shared with other conditions with similar pathophysiological mechanisms. Patients with FCHL are at an increased risk of cardiovascular disease and mortality and have a high frequency of comorbidity with other metabolic conditions such as type 2 diabetes, non-alcoholic fatty liver disease, steatohepatitis, and the metabolic syndrome. Management usually requires lipid-lowering therapy directed toward reducing cholesterol and triglyceride concentrations along with cardiovascular risk protection. In recent years, the number of research studies on FCHL has been decreasing, mainly due to a lack of recognition of its impact on disease burden and comorbidity and the complexity in identifying probands for studies. This creates areas of opportunity to develop research for FCHL in epidemiology, genetics, pathophysiology, therapeutics, and cardiovascular risk management, which are discussed in depth in this review. (REV INVEST CLIN. 2018;70:224-36).

Alirocumab in the management of primary hypercholesterolaemia or mixed dyslipidaemia: A budget impact analysis – Italian perspective

Alirocumab in the management of primary hypercholesterolaemia or mixed dyslipidaemia: A budget impact analysis – Italian perspective

Performance of LDL-C calculated with Martin's formula compared to the Friedewald equation in familial combined hyperlipidemia

Background and aimsA novel method to estimate low density lipoprotein cholesterol (LDL-C) has been proposed by Martin et al. This may permit a more accurate estimation of cardiovascular risk, however, external validation is needed. Here, the performance of LDL-C using this new method (LDL-N) is compared with LDL-C estimated with Friedewald equation (LDL-F) in familial combined hyperlipidemia (FCHL), a common primary dyslipidemia in which apolipoprotein B containing particle composition is abnormal and interferes with LDL-C estimation. MethodsA total of 410 FCHL subjects were included. LDL-C was estimated with both the Friedewald equation (LDL-F) and the novel formula (LDL-N). Apolipoprotein B levels and non- HDL-C were recorded. The correlation and concordance between LDL-F and LDL-N and both Apolipoprotein B and non-HDL-C levels were calculated. Analysis stratifying for triglyceride tertiles and FCHL lipid phenotypes was also carried out. ResultsThe correlations between LDL-N and Apo B and non-HDL-C were ρ = 0.777 (95%CI 0.718–0.825) and ρ = 0.735 (95%CI 0.648–0.816), respectively. The corresponding correlations for LDL-F were ρ = 0.551(95%CI 0.454–0.637) and ρ = 0.394 (95%CI 0.253–0.537), respectively. In mixed dyslipidemia or isolated hypertriglyceridemia, these correlations were significantly better using LDL-N. With respect to concordance, LDL-N performed significantly better than LDL-F when considering apoB <90 mg/dL (κLDL-N = 0.495 vs. κLDL-F = 0.165) and non-HDL-C <130 (κLDL-N = 0.724 vs. κLDL-F = 0.253). ConclusionsIn FCHL, LDL-C estimation using Martin's formula showed greater correlation and concordance with non-HDL-C and Apo B compared with the Friedewald equation.

Single, short in-del, and copy number variations detection in monogenic dyslipidemia using a next-generation sequencing strategy.

Optimal molecular diagnosis of primary dyslipidemia is challenging to confirm the diagnosis, test and identify at risk relatives. The aim of this study was to test the application of a single targeted next-generation sequencing (NGS) panel for hypercholesterolemia, hypocholesterolemia, and hypertriglyceridemia molecular diagnosis. NGS workflow based on a custom AmpliSeq panel was designed for sequencing the most prevalent dyslipidemia-causing genes (ANGPTL3, APOA5, APOC2, APOB, GPIHBP1, LDLR, LMF1, LPL, PCSK9) on the Ion PGM Sequencer. One hundred and forty patients without molecular diagnosis were studied. In silico analyses were performed using the NextGENe software and homemade tools for detection of copy number variations (CNV). All mutations were confirmed using appropriate tools. Eighty seven variations and 4 CNV were identified, allowing a molecular diagnosis for 40/116 hypercholesterolemic patients, 5/13 hypocholesterolemic patients, and 2/11, hypertriglyceridemic patients respectively. This workflow allowed the detection of CNV contrary to our previous strategy. Some variations were found in previously unexplored regions providing an added value for genotype-phenotype correlation and familial screening. In conclusion, this new NGS process is an effective mutation detection method and allows better understanding of phenotype. Consequently this assay meets the medical need for individualized diagnosis of dyslipidemia.

Dietary polyunsaturated fatty acids mediate the inverse association of stearoyl-CoA desaturase activity with the risk of fatty liver in dyslipidaemic individuals.

The activity of stearoyl-CoA desaturase-1 (SCD1) is increased in non-alcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) inhibit SCD1, but clinical studies on whether all dietary PUFA species are equal in SCD1 inhibition are scarce. Serum phospholipids are an objective proxy of dietary intake of plant-derived PUFA (C18:2n-6, C18:3n-3) and marine-derived PUFA (C20:5n-3, C22:6n-3). In 355 participants with primary dyslipidemia, we cross-sectionally investigated whether the presumed association between surrogate markers of NAFLD and SCD1 activity is mediated by intake of PUFA, and, if it is, what PUFA species are relevant in this regard. We determined the fatty acid profile of serum phospholipids by gas chromatography, and used the ratio C16:1n-7/C16:0 as a marker of SCD1 activity. NAFLD was diagnosed by values ≥ 60 in the fatty liver index (FLI), a surrogate recently validated against ultrasonography. FLI ≥ 60 was detected in 37.5% (n = 133) of study participants. In a multivariate model, SCD1 activity showed an expected significant association with the risk of NAFLD, with odds ratio (OR) (95% confidence interval) of 1.44 (1.04-2.01) for each 0.01 increase. In a model further allowing the stepwise inclusion of plant-derived PUFA, marine-derived PUFA, and total PUFA (vegetable + marine), total PUFA replaced SCD1 activity as a significant (inverse) association of NAFLD, with OR 0.89 (0.81-0.99). Total PUFA, regardless of their origin, mediates the relationship between SCD1 activity and NAFLD. This provides a new insight in the protective effects of PUFA against NAFLD, heretofore mostly focussed on PUFA species from marine origin.

Case-control study on PCSK9 R496W (rs374603772) and D374Y (rs137852912) mutations in Turkish patients with primary dyslipidemia.

Objective:The aim of this study was to investigate the relationships between F216L (rs28942112), R496W (rs374603772), S127R (rs28942111), and D374Y (rs137852912) PCSK9 gain-of-function (GOF) mutations and primary dyslipidemia and serum lipid levels in patients with primary dyslipidemia.Methods:In this case-control study, DNA was isolated from blood samples collected from patients diagnosed with primary dyslipidemia in cardiology outpatient clinic of Ege University (n=200) and healthy individuals (n=201). F216L, R496W, S127R, and D374Y GOF mutations in the PCSK9 gene were evaluated and genotyped according to the results of melting curve analysis performed in a real-time polymerase chain reaction (PCR) 480 instrument using specific primers for each mutation.Results:There were statistically significant differences between the patient and individuals in control groups in the R496W and D374Y mutations (χ2=10.742 p=0.005; χ2=6.078 p=0.048, respectively). In addition, triglyceride levels in patients with primary dyslipidemia heterozygous for R496W and D374Y mutations were 12.8-fold (p=0.015) and 3.4-fold (p=0.03) higher than that in mutant and wild-type genotype, respectively. Additionally, in the entire study group (n=401), PCSK9 R496W and D374Y mutation carriers had increased total cholesterol (p=0.021), triglycerides (p=0.0001), HDL cholesterol (p=0.028), and low-density lipoproteins (LDL) cholesterol (p=0.028) levels. However, F216L (rs28942112) and S127R (rs28942111) mutations were not detected in patients with primary dyslipidemia and healthy controls.Conclusion:We conclude that the PCSK9 R496W (rs374603772) and D374Y (rs137852912) GOF mutations may be significant risk factors in the development of primary dyslipidemia and may have significant impact on lipid parameters in general population.

Alirocumab in the management of primary hypercholesterolaemia or mixed dyslipidaemia: A budget impact analysis – Italian perspective

Recent evidence suggests that adding protein convertase subtilisin/kexin type 9 inhibitors to current lipid-lowering therapies may result in unprecedented reductions in low-density lipoprotein chol...

Effects of short-term fasting on lipid and lipoprotein concentrationes in healthy lean dogs

Introduction. Analysis of canine lipoprotein fractions after agarose gel electrophoresis (agEF) separation could be an important diagnostic tool in primary and secondary dyslipidemia diagnosis. The aim of this study was to measure concentrations of triglycerides and cholesterol and to analyze lipoprotein fractions in dogs after basal (12 hours) and short-term (24 and 36 hours) fasting, i.e., frequent conditions in clinical practice. Materials and Methods. Blood samples were collected from six lean dogs of both sexes and different breeds, after 12, 24 and 36 hours of fasting. Concentrations of glucose, triglycerides and cholesterol were determined on an automated wet biochemistry analyzer, lipoprotein fractions were separated by agEF and leukocyte numbers were assessed on an automated hematology analyzer. Results and Conclusions. Results showed there was no significant change in glucose, triglyceride and cholesterol concentrations nor in leukocyte numbers during dog fasting. Moreover, there was no change in ?1- and ?2-fractions, but there was a significant decrease in pre?- and ?-fraction of lipoproteins. It is know that high density lipoproteins (HDL) have ?-mobility and very low density (VLDL) and low density lipoproteins (LDL) have pre?- and ?-mobility. Thus, it is possible that reverse cholesterol transport maintained by HDL is not affected during short-term fasting. On the contrary, synthesis of VLDL and formation of LDL are probably decreased because endogenous synthesis of triglycerides is decreased or their clearance is increased.

Management and Follow-Up of Dyslipidemia in Primary Health Care Setting

Introduction: Management of dyslipidemia is an important part of most practice guidelines with many variations between these guidelines. Unfortunately, usually these guidelines are not followed widely on the level of primary care, possibly due to insufficient qualification of health care staff in primary care, non-participation in recent guidelines, and unrealistic target assigned to patients that leads them to non-compliance with medication and follow-up. Methodology: We conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE, January 2001, through February 2017. The following search terms were used: dyslipidemia, primary health care dyslipidemia management, follow-up of dyslipidemia. Aim: In this review, we aimed at evaluating the management expected from primary health care for risk assessment, treatment and follow-up of patients with dyslipidemia. Conclusion: Many guidelines exist for the proper management of dyslipidemia in the primary care setting. Screening is crucial for preventing the cardiovascular sequelae of dyslipidemia. Management modalities include lifestyle modification and pharmacotherapy, while the significance of follow-up cannot be neglected.

New treatment options for lipid-lowering therapy in subjects with type 2 diabetes

Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein. In addition, insulin resistance promotes the production of small dense low-density lipoprotein (LDL) and reduces high-density lipoprotein (HDL) production. Cardiovascular disease remains a leading cause of morbidity and mortality in diabetic patients. Previous results support the role for small, dense LDL particles in the etiology of atherosclerosis and their association with coronary artery disease. Moreover, lowering LDL cholesterol reduces the risk of cardiovascular death. Therefore, the European guidelines for the management of dyslipidemias recommend an LDL cholesterol goal<100mg/dL in diabetic subjects without cardiovascular events. Moreover, if triglycerides (TG) are elevated (>400mg/dL), they recommend a non-HDL cholesterol goal<130mg/dL in diabetic individuals without cardiovascular events. Statins are the first line of LDL-lowering therapy in diabetic patients and combined therapy with ezetimibe and statins could be useful in very high cardiovascular risk diabetic subjects. Furthermore, the effect of a fibrate as an add-on treatment to a statin could improve the lipid profile in diabetic individuals with high TG and low HDL cholesterol. Regarding new therapies, recent data from phase III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably decrease LDL cholesterol. Thus, they may be useful in diabetic patients with concomitant diseases such as familial dyslipidemia, recurrent cardiovascular events, and elevated LDL cholesterol after second drug administration in addition to maximal statin dose or statin intolerance.

Planned secondary wound closure at the circular stapler insertion site after laparoscopic gastric bypass reduces postoperative morbidity, costs, and hospital stay

The aims of the present study were to assess whether planned secondary wound closure at the insertion site of the circular stapler reduces wound infection rate and postoperative morbidity after laparoscopic Roux-en-Y gastric bypass (RYGB) and to identify independent predictive factors increasing the risk for wound infections after RYGB. This paper is a retrospective single-center analysis of a prospectively collected database of 1400 patients undergoing RYGB surgery in circular technique between June 2000 and June 2016. Planned secondary wound closure at the circular stapler introduction site was performed at postoperative day 3 in 291 (20.8%) consecutive patients and compared to a historical control of 1109 (79.2%) consecutive patients with primary wound closure. Independent predictive factors for wound infection were assessed by multivariable analysis. Secondary wound closure significantly decreased wound infection rate from 9.3% (103/1109) to 1% (3/291) (p<0.001) leading to a shorter hospital stay (mean 9 (SD8) vs. 7days (SD2), p<0.001), lower costs (p=0.039), and reduced postoperative morbidity (mean 90-day Comprehensive Complication Index (CCI) 7.4 (SD14.0) vs. 5.1 (SD11.1) p=0.008) when compared to primary wound closure. Primary wound closure, dyslipidemia, and preoperative gastritis were independent predictive risk factors for developing wound infections both in the univariate (p<0.001; p=0.048; p=0.003) and multivariable analysis (p<0.001; p=0.040; p=0.012). Further, on multivariable analysis, the female gender was a predictive factor (p=0.034) for wound infection development. Secondary wound closure at the circular stapler introduction site in laparoscopic RYGB significantly reduces the overall wound infection rate as well as postoperative morbidity, costs, and hospital stay when compared to primary wound closure.