European guidelines for the treatment of dyslipidaemias: New concepts and future challenges.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity worldwide. Low-density lipoprotein cholesterol (LDL-C) is one of the most important causal factors for ASCVD. Based on the evidence of the clinical benefits of lowering LDL-C, the current 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines provide guidance for optimal management of people with dyslipidaemia. These guidelines include new and revised concepts, with a general tightening of LDL-C goals to be achieved, especially for patients at high and very high cardiovascular risk, based on the results of clinical trials of the recently approved drugs for the treatment of hypercholesterolaemia. However, some issues are still open for discussion. Among others, the concept of lifetime exposure to elevated LDL-C levels will probably drive the pharmacological approach and future guidelines. In addition, other factors such as non-HDL-C, apolipoprotein B, and lipoprotein(a) are becoming increasingly important in determining cardiovascular risk. Finally, there is the question of whether combination therapy should be used as the first step to maximise the effectiveness of the pharmacological approach, avoiding the stepwise approach, which is likely to have a detrimental effect on adherence. Given the ever-changing landscape and the availability of new drugs targeting other important lipids, future guidelines will need to consider all these issues.

Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century.

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered. There are no medical treatments available and complex high-risk surgeries represent the only available option in severe cases. A systematic review was performed to summarize the current evidence on AS in HoFH and to determine whether pharmacological treatment (statins) have had an impact on clinical presentation, phenotype and clinical course over the past nine decades (PROSPERO CRD42021250565). METHODS AND RESULTS: MEDLINE, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, PubMed, AfricaWide, and Scopus were searched from inception to 10 November 2021. Searches identified 381 publications, of which 19 were retained; they were cross-sectional or retrospective studies. Separately, 108 individual case reports were described. Within the 424 HoFH cases, AS was identified in 57% of patients in the pre-statin era vs. 35% in patients reported more recently (>2000, long-term statin period). With an increase in longevity due to statins and lipoprotein apheresis, a change in the proportion of patients with SVAS and VAS with a SVAS:VAS ratio of 47:53 and 10:90 for HoFH patients not on statin and on long-term statin, respectively, was noted. CONCLUSION: These data suggest that SVAS and VAS are frequent in HoFH and that the phenotype has shifted towards calcific VAS as statins and lipoprotein apheresis improve survival in these patients.

Polymorphism PLIN1 11482 G>A interacts with dietary intake to modulate anthropometric measures and lipid profile in adults with normal-weight obesity syndrome.

Evidence shows that genetic polymorphisms in perilipin 1 gene (PLIN1) are associated with excessive accumulation of body fat and disturbances in cardiometabolic markers. Therefore, the aim of this study was to verify whether the SNP PLIN1 11482 G>A (rs894160) interacts with nutrient intake, anthropometric, body composition and cardiometabolic markers in adults with normal-weight obesity (NWO) syndrome. A cross-sectional study was carried out with 116 individuals aged 20-59 years, with normal BMI and high percentage of body fat. Anthropometric and body composition measures, glycaemic control and serum lipid markers, SNP PLIN1 11482 G>A and nutrient intake were evaluated. Interactions between nutrient intake and the SNP were determined by regression models and adjusted for potential confounders. The SNP frequency was 56·0 % GG, 38·8 % GA and 5·2 % AA. Anthropometric measures and biochemical markers were not different according to genotype, except for total cholesterol (TC), LDL-cholesterol and non-HDL-cholesterol concentrations. However, important interactions between the SNP and dietary intake were observed. Carbohydrate intake interacted with the SNP PLIN1 11482 G>A to modulate waist circumference (WC) and the homeostatic model assessment of insulin resistance index. Interaction of lipid intake and the SNP modulated TC and LDL-cholesterol concentrations, and the interaction between protein intake and the SNP tended to modulate weight, WC and BMI. The SNP PLIN1 11482 G>A seems to modulate responses in anthropometric and lipid profile biomarkers of subjects with NWO depending on the dietary macronutrient composition, which may have long-term impact on cardiometabolic markers.

Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence. OBJECTIVES: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins. METHODS: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins. RESULTS: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation. CONCLUSIONS: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.

Investigating the effect of an education programme on diabetes and lipid lowering medication usage following coronary artery bypass graft surgery.

BACKGROUND: Guidelines advocate multifactorial cardiovascular risk management in patients with diabetes and atherosclerotic cardiovascular disease. AIM: In hospitalised patients with diabetes following coronary artery bypass graft (CABG), we aimed to evaluate the impacts of decision-support algorithms for optimising glycaemia and lipid-lowering. We also assessed the safety of initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors near time of hospital discharge. METHODS: This was a single-site, pre- and post-intervention analysis of glucose and lipid management in consecutive hospitalised patients with diabetes undergoing CABG surgery. The intervention involved education and decision-support algorithms designed by a multidisciplinary committee to guide cardiac surgery unit clinicians. RESULTS: A total of 200 patients were included in the study. The pre- and post-intervention groups had similar baseline characteristics (HbA1c 7.9 ± 1.9% vs 8.1 ± 1.8%). Of 4092 blood glucose measurements, the incidence of levels between 5 and 10 mmol/L was not different post-intervention (55.5% vs 57.0%; P = 0.441). Fewer endocrinology consultations occurred (59.0% vs 45.0%; P = 0.048) and rates of hypoglycaemia remained low. High-intensity statin was prescribed in >90% pre- and post-intervention, although non-statin lipid-lowering agents remained <10% despite patients not achieving LDL-C targets. No 30-day readmissions for diabetic ketoacidosis occurred in patients prescribed SGLT2 inhibitors. CONCLUSION: The intervention did not improve inpatient glycaemia or increase non-statin lipid-lowering prescriptions in patients with diabetes following CABG surgery but did reduce reliance on specialty input. Initiation of SGLT2 inhibitor therapy near time of hospital discharge was not associated with safety concerns. Alternative interventions or strategies are required to optimise glycaemia and non-statin lipid-lowering therapy prescribing in this setting.

TAG-glucose (TyG) index in childhood: an estimate of cut-off points and the relation to cardiometabolic risk in 4- to 9-year-old children.

OBJECTIVE: To propose cut-off points for the TAG-glucose (TyG) index in Brazilian children and evaluate the link to cardiometabolic risk. DESIGN: A cross-sectional study with children from a municipality in Minas Gerais, Brazil. Anthropometric (weight, height, waist circumference and waist:height ratio), biochemical (lipid and glucose profile) and blood pressure (BP) tests were performed. Using the receiver operating characteristic curve, cut-off points for the TyG index were proposed according to sex using homoeostasis model of assessment - insulin resistance (IR) as the reference method. SETTING: Viçosa, MG, Brazil. PARTICIPANTS: Children aged 4-9 years (n 515). RESULTS: The TyG index cut-off points to identify the risk of IR were 7·9 and 8·1 for boys and girls, respectively. We observed that 48·7 % of the children had an increased TyG index. The increased TyG index was associated with overweight, total body and central fat, increased BP and altered lipid profile. Children with an increased TyG index had a higher accumulation of cardiometabolic risk factors. CONCLUSIONS: According to the cut-off points proposed by the current study, children at risk of IR estimated by the TyG index presented a higher cardiometabolic risk, including isolated risk factors, as to the higher accumulation of these.

A Systematic Approach to Assess the Activity and Classification of PCSK9 Variants.

BACKGROUND: Gain of function (GOF) mutations of PCSK9 cause autosomal dominant familial hypercholesterolemia as they reduce the abundance of LDL receptor (LDLR) more efficiently than wild-type PCSK9. In contrast, PCSK9 loss of function (LOF) variants are associated with a hypocholesterolemic phenotype. Dozens of PCSK9 variants have been reported, but most remain of unknown significance since their characterization has not been conducted. OBJECTIVE: Our aim was to make the most comprehensive assessment of PCSK9 variants and to determine the simplest approach for the classification of these variants. METHODS: The expression, maturation, secretion, and activity of nine well-established PCSK9 variants were assessed in transiently transfected HEK293 cells by Western blot and flow cytometry. Their extracellular activities were determined in HepG2 cells incubated with the purified recombinant PCSK9 variants. Their binding affinities toward the LDLR were determined by solid-phase immunoassay. RESULTS: LDLR expression increased when cells were transfected with LOF variants and reduced when cells were transfected with GOF variants compared with wild-type PCSK9. Extracellular activities measurements yielded exactly similar results. GOF and LOF variants had increased, respectively reduced, affinities for the LDLR compared with wild-type PCSK9 with the exception of one GOF variant (R218S) that showed complete resistance to inactivation by furin. All variants were expressed at similar levels and underwent normal maturation and secretion patterns except for two LOF and two GOF mutants. CONCLUSIONS: We propose that transient transfections of HEK293 cells with a plasmid encoding a PCSK9 variant followed by LDLR expression assessment by flow cytometry is sufficient to reliably determine its GOF or LOF status. More refined experiments should only be used to determine the underlying mechanism(s) at hand.

Patient characteristics, treatment patterns, and adherence to lipid-lowering therapies following an acute coronary syndrome.

Despite dyslipidaemia management guidelines, many patients do not reach low-density lipoprotein cholesterol targets due to insufficiently intensive regimens or lack of adherence to their medication. This was a retrospective cohort study on the Pharmacoepidemiologic General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Patients included were ≥ 18 years old who suffered an ACS between 2013 and 2016, and treated with lipid-lowering therapy (LLT) at hospital discharge or within 92 days. Patients were followed up to 12 months' post index ACS, a new cardiovascular event, loss to follow-up or death. Treatment intensity (high, moderate and low intensity statins ± ezetimibe) and adherence (proportion of days covered > 80%) are described. A total of 2,695 patients were included; mean age [SD] was 63.1 [12.8] years, and 77% were men. High, moderate and low intensity statins were started in 56% (1,520), 36% (971), and 3% (86) of patients, respectively. A further 2% (46) were on statin/ezetimibe combination, 2% (42) on other LLT and 1% (30) on ezetimibe alone. At follow-up, around 70% of patients were adherent to LLT, with those on moderate intensity treatments showing better adherence (76%) than those on low (63%) or high (67%) intensity treatments. Despite guideline recommendations, many patients following an ACS are not treated with high intensity statins, and adherence remains far from optimal. Effort should be made to increase the proportion of patients treated with high intensity statins following an ACS and to further improve treatment adherence.

Physical inactivity and excessive sucrose consumption are associated with higher serum lipids in subjects with Taq1B CETP polymorphism.

BACKGROUND: Dyslipidaemias result from the interaction between genetic and environmental factors, including diet disequilibrium and physical inactivity. Among the genetic factors associated with serum lipids, the Taq1B CETP polymorphism has been investigated. The B1 allele has been considered as a risk factor for dyslipidaemia because of its association with greater CETP levels and higher serum triglycerides. The present study aimed to determine the role of the Taq1B polymorphism with lipid and anthropometric variables and its interaction with diet and physical activity. METHODS: In total, 215 subjects were enrolled in this cross-sectional study. Diet intake was evaluated using a 3-day food consumption record and physical activity was determined in accordance with World Health Organization recommendations. The Taq1B CETP polymorphism was determined by allelic discrimination. RESULTS: Subjects with the B1B2/B2B2 genotype, who had a sucrose consumption ≥5% of the total kcal day-1 , had higher levels of total cholesterol (TC) [165.55 (142.21-188.89) mg dL-1 versus 200.19 (184.79-215.60) mg dL-1 ; P for interaction = 0.034] and low-density lipoprotein [99.29 (75.52-123.05) mg dL-1 versus 128.64 (113.59-143.69) mg dL-1 ; P for interaction = 0.037] than subjects with the B1B1 genotype. Subjects who did not perform physical activity and had the B1B2/B2B2 genotype showed significantly higher levels of TC [177.48 (161.36-193.60) mg dL-1 versus 194.49 (185.43-203.56) mg mL-1 ; P for interaction = 0.033] than subjects with the B1B1 genotype. CONCLUSIONS: We provide evidence that subjects with inadequate environmental factors carriers of the polymorphic genotype had higher serum lipid levels than subjects with the B1B1 genotype.

Dyslipidaemia in adults with type 1 diabetes-when to treat?

Dyslipidaemia is an important modifiable risk factor contributing to the increased risk of atherosclerotic cardiovascular disease in diabetes. However, determining when to initiate statin therapy in young adults with type 1 diabetes mellitus (T1DM) can often be challenging. This is due to a relative paucity of data in this area to guide management and for developing T1DM-specific risk engines. Current recommendations from international guidelines offer differing approaches to cardiovascular risk stratification and management of dyslipidaemia in T1DM. We present a clinical vignette and comment on the use of nontraditional methods of cardiovascular risk stratification. The strategy for managing dyslipidaemia in young T1DM should be individualized, and recommendations from guidelines should serve to inform clinical judgement.

ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1.

BACKGROUND: In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (ß1, ß2, and ß3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders. METHODS: We studied 329 non-related adults (33.1% men and 66.9% women), aged 18-36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥25.1-29.9 kg/m2) subjects, and obese (≥30 kg/m2). RESULTS: In the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele. CONCLUSION: The results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.

Mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotics.

CVD affect a large proportion of the world's population, with dyslipidaemia as the major risk factor. The regular consumption of both probiotic bacteria and yeast has been associated with improvement in the serum lipid profile. Thus, the present review aims to describe and discuss the potential mechanisms responsible for the hypocholesterolaemic effect of regular consumption of probiotic bacteria and yeast. Regarding the hypocholesterolaemic effect of probiotic bacteria, the potential mechanisms responsible include: deconjugation of bile salts; modulation of lipid metabolism; and decreased absorption of intestinal cholesterol through co-precipitation of intestinal cholesterol with the deconjugated bile salts, incorporation and assimilation of cholesterol in the cell membrane of the probiotics, intestinal conversion of cholesterol in coprostanol, and inhibition of the expression of the intestinal cholesterol transporter Niemann-Pick C1 like 1 (NPC1L1) in the enterocytes. The potential mechanisms responsible for the hypocholesterolaemic effect of probiotic yeasts include: deconjugation of bile salts; co-precipitation of intestinal cholesterol with the deconjugated bile salts; incorporation and assimilation of cholesterol in the cell membrane; and inhibition of hepatic cholesterol synthesis. The regular consumption of probiotic bacteria and yeast, as a non-pharmaceutical approach to help manage cardiovascular risk, holds promise, according to the beneficial hypocholesterolaemic effects described herein. However, the hypocholesterolaemic effects vary according to the strains used, the physiological state of the host, and the type of diet to which the probiotics are added. Further studies are necessary to fill the gaps with regard to the knowledge related to this topic.

Changes in body fatness affect cardiovascular outcomes more than changes in physical activity.

OBJECTIVE: The aim of this study was to analyse whether changes in physical activity and body fatness are related to modifications in cardiovascular risk factors among adolescents. Material and methods A sample of 89 healthy adolescents was recruited for this study. We assessed habitual physical activity, body fat percentage, arterial thickness, blood sample, and biological maturation. Multivariate models were used to analyse the relationships between independent and dependent variables. RESULTS: Physical activity (mean difference: 429.4 steps [95% confidence interval=-427 to 1286]) and body fatness (mean difference: -0.7% [95% confidence interval=-1.6-0.2]) remained stable during the study period. Independent of changes in physical activity, for each percentage increase in body fatness, femoral intima-media thickness increased by 0.007 mm (ß=0.007 [95% confidence interval=0.001-0.013]). Longitudinal relationships were found for high-density lipoprotein-cholesterol (ß=-0.477 mg/dl [95% confidence interval=-0.805 to -0.149]) and triacylglycerol (ß=2.329 mg/dl [95% confidence interval=0.275-4.384]). CONCLUSION: Changes in body fatness are more important than the amount of physical activity on cardiovascular and metabolic risks.

[A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia].

Objective: To evaluate the efficacy of oral nattokinase (NK) in the reduction of common carotid artery intimal medial thickness (CCA-IMT) and carotid artery plaque size and in lowering blood lipids, and to explore the underlying mechanism of actions of NK and its potential clinical use. Methods: All enrolled patients were from the Out-Patient Clinic of the Department of TCM at the 3(rd) Affiliated Hospital of Sun Yat-sen University. Using randomised picking method, all patients were randomly assigned to one of two groups, NK and Statin (ST) group. NK Group-patients were given NK at a daily dose of 6 000 FU and ST Group-patients were treated with statin (simvastatin 20 mg) daily. The treatment course was 26 weeks. CCA-IMT, carotid plaque size and blood lipid profile of the patients were measured before and after treatment. Results: A total of 82 patients were enrolled in the study and 76 patients (NK 39, ST 37) completed the study. Following the treatments for 26 weeks, there was a significant reduction in CCA-IMT and carotid plaque size in both groups compared with the baseline before treatment. The carotid plaque size and CCA-IMT reduced from(0.25±0.12)cm(2) to (0.16±0.10)cm(2) and from (1.13±0.12)mm to (1.01±0.11)mm, repectively. The reduction in the NK group was significantly profound (P<0.01, 36.6% reduction in plaque size in NK group versus 11.5% change in ST group). Both treatments reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). While the reduction in both groups was shown to be statistically significant (P<0.01), the reduction of TC, LDL-C and TG in ST group was significantly greater (P<0.05). In addition, NK significantly increased the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05), in contrast, HDL-C in the ST group did not change. The lipid lowering effect observed in the NK group was not correlated to the reduction of CCA-IMT and carotid artery plaque size (r=0.35, P=0.09). Conclusions: Our findings from this pioneer clinical study suggests that daily NK supplementation is an effective way to manage the progression of atherosclerosis and potentially may be a better alternative to statins which are commonly used to reduce atherosclerosis and further to prevent cardiovascular attack and stroke in patients. The mechanism underlying the reduction of carotid atherosclerosis by NK may be independent from its lipid-lowering effect, which is different from that of statins.

The role of active brown adipose tissue in human metabolism.

PURPOSE: The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing (18)F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively and prospectively analysed the (18)F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. RESULTS: A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). CONCLUSION: Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD.

Pattern of dyslipidaemia and impact of increasing age and duration of type 2 diabetes mellitus on dyslipidaemia, insulin levels and insulin resistance.

OBJECTIVE: To study the pattern of dyslipidaemia in Type 2 Diabetes Mellitus patients and to determine the correlation of increasing age and duration of the disease with dyslipidaemia, insulin level and insulin resistance in diabetic patients. METHODS: The cross-sectional case-control study was conducted at Combined Military Hospital, Rawalpindi, and Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi, Pakistan from June 2011 to June 2012, and comprised patients of type 2 diabetes mellitus and healthy controls. Serum levels of total cholesterol, triglycerides, low density lipoprotein, high-density lipoprotein and insulin in both the cases and the controls. Insulin resistance was calculated by Homeostatic Model of Assessment of insulin resistance. Correlation between increasing age and duration of the disease was determined using biochemical parameters. SPSS 17 was used for statistical analysis. RESULTS: Of the 112 subjects in the study, 72(64%) were patients and 40(36%) were healthy controls. Among the cases, hypertriglyceridaemia was the commonest in 44(61%) followed by low-density-lipoprotein-hypercholesterolaemia 36(50%). Among the controls, 20(50%) subjects had low-density-lipoprotein-hypercholesterolaemia, followed by hypertriglyceridaemia in 17(42.5%). Duration of the disease was not found to be correlated with dyslipidaemia or insulin resistance (p>0.05). There was strong negative correlation of duration of the disease with serum insulin levels (p=0.03). Age showed no significant correlation with dyslipidaemia, serum insulin levels or insulin resistance on regression analysis (p>0.05 each). CONCLUSIONS: In type diabetes mellitus, hypertriglyceridaemia was the commonest dyslipidaemia whereas hypercholesterolaemia was a risk factor in healthy individuals. Besides, the duration of disease was inversely correlated with serum insulin levels and positively correlated with dyslipidaemia.

Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment.

Risk of cardiovascular (CV) disease is increased among RA patients. High inflammatory burden associated with RA appears to be a key driver of the increased cardiovascular risk. Inflammation is linked with accelerated atherosclerosis and associated with a paradoxical inversion of the relationship between CV risk and lipid levels in patients with untreated RA, recently coined the lipid paradox. Furthermore, the inflammatory burden is also associated with qualitative as well as quantitative changes in lipoproteins, with the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol significantly altered. RA therapies can increase lipid levels, which may reflect the normalization of lipids due to their inflammatory-dampening effects. However, these confounding influences of inflammation and RA therapies on lipid profiles pose challenges for assessing CV risk in RA patients and interpretation of traditional CV risk scores. In this review we examine the relationship between the increased inflammatory burden in RA and CV risk, exploring how inflammation influences lipid profiles, the impact of RA therapies and strategies for identifying and monitoring CV risk in RA patients aimed at improving CV outcomes.

Overview of a collaborative global effort to address the burden of familial hypercholesterolaemia.

This is an overview of the EAS Familial Hypercholesterolaemia (FH) Studies Collaboration (FHSC) global consortium and registry (established 2015), which broadly addresses the global burden of FH. Eighty-seven National Lead Investigators from 74 countries form this expanding global consortium, and this global registry currently includes pooled data on 70,000 participants from participating countries to facilitate FH surveillance. Published first results from this global registry concluded that FH is diagnosed late, and management of LDL-cholesterol falls below guideline recommendations, and therefore earlier detection of FH and wider use of combination therapy is required. Further FHSC studies will follow on updated data including new countries, participants and variables, and non-DNA genetic information, and on the remaining cohorts in the registry. FHSC cross-sectional collaborative global studies are expected to promote FH detection earlier in life to subsequently initiate early lipid lowering therapy to reduce lifelong exposure to cumulative LDL-cholesterol thus reducing cardiovascular disease risk.

Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study.

AIMS: Omega-3 fatty acids and fenofibrates have shown some beneficial cardiovascular effects; however, their efficacy has not been compared. This study aimed to compare the effectiveness of currently available omega-3 fatty acids and fenofibrate for reducing major adverse cardiovascular events (MACE). METHODS AND RESULTS: From a nationwide population-based cohort in South Korea (2008-2019), individuals with metabolic syndrome (≥30 years) who received statin with omega-3 fatty acids and those receiving statin with fenofibrate were matched by propensity score (n = 39 165 in both groups). The primary outcome was MACE, including ischaemic heart disease (IHD), ischaemic stroke (IS), and death from cardiovascular causes. The risk of MACE was lower [hazard ratio (HR), 0.79; 95% confidence interval (CI), 0.74-0.83] in the fenofibrate group than in the omega-3 fatty acid group. Fenofibrate was associated with a lower incidence of IHD (HR, 0.72; 95% CI, 0.67-0.77) and hospitalization for heart failure (HR, 0.90; 95% CI, 0.82-0.97), but not IS (HR, 0.90; 95% CI, 0.81-1.00) nor death from cardiovascular causes (HR, 1.07; 95% CI, 0.97-1.17). The beneficial effect of fenofibrate compared to omega-3 fatty acids was prominent in patients with preexisting atherosclerotic cardiovascular disease and those receiving lower doses of omega-3 fatty acids (≤2 g per day). CONCLUSION: In a real-world setting, fenofibrate use was associated with a lower risk of MACE compared with low-dose omega-3 fatty acids when added to statins in people with metabolic syndrome.