Family sitosterolemia: report of two cases in Colombia. / Sitosterolemia familiar: reporte de dos casos en Colombia.

Sitosterolemia is an autosomal recessive and very rare disease. Its main characteristic is that there is a greater absorption and a decrease in the excretion of sterols, which leads to them being deposited in tissues. It is given by mutations in the ABCG5 or ABCG8 genes found on chromosome 2p21. In this clinical note, we describe the first two patients with familial sitosterolemia described in Colombia, brothers, one of them with xanthomas in extremities as the only symptom, and the other, completely asymptomatic. Genetic studies were performed as a diagnostic test in both patients, where a pathogenic homozygous variant could be identified in the ABCG8 gene in the first case (symptomatic), and a heterozygous variant in the ABCG8 gene in the second case (asymptomatic); the first patient has responded to treatment with ezetimibe. In conclusion, xanthomas should be studied in depth in pediatric age as they may be the only visible sign of such complex and hereditary diseases as familial sitosterolemia, which can be controlled and prevent cardiovascular complications of the disease.

Role of Insulin Resistance in the Development of Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: From Bench to Patient Care.

Insulin resistance is implicated in both the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progression from steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma, which is known to be more common in people with type 2 diabetes. This article reviews the role of insulin resistance in the metabolic dysfunction observed in obesity, type 2 diabetes, atherogenic dyslipidemia, and hypertension and how it is a driver of the natural history of NAFLD by promoting glucotoxicity and lipotoxicity. The authors also review the genetic and environmental factors that stimulate steatohepatitis and fibrosis progression and their relationship with cardiovascular disease and summarize guidelines supporting the treatment of NAFLD with diabetes medications that reduce insulin resistance, such as pioglitazone or glucagon-like peptide 1 receptor agonists.

Association between hepatic steatosis and lipoprotein(a) levels in non-alcoholic patients: A systematic review.

BACKGROUND AND OBJECTIVES: It is well known that lipid abnormalities exist in the context of non-alcoholic fatty liver disease (NAFLD). The association between lipoprotein(a) [Lp(a)] levels and NAFLD is poorly understood. The main objective of the present study was to assess the association between Lp(a) levels and NAFLD. METHODS: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42023392526). A literature search was performed to detect studies that evaluated the association between Lp(a) levels, NAFLD and steatohepatitis (NASH). RESULTS: Ten observational studies, including 40,045 patients, were identified and considered eligible for this systematic review. There were 9266 subjects in the NAFLD groups and 30,779 individuals in the respective control groups. Five studies evaluated patients with NAFLD (hepatic steatosis was associated with lower Lp(a) levels in four studies, while the remaining showed opposite results). Two studies evaluating NASH patients showed that Lp(a) levels were not different compared to controls. However, the increment of Lp(a) levels was correlated with liver fibrosis in one of them. In addition, one study analyzed simultaneously patients with NAFLD and NASH, showing a neutral result in NAFLD patients and a positive relationship in NASH patients. Two studies that included patients with the new definition of metabolic-associated fatty liver disease (MAFLD) also showed neutral results. CONCLUSION: Although there could be an association between Lp(a) levels and hepatic steatosis, the results of the studies published to date are contradictory and not definitive.

Relationship between epicardial adipose tissue, systemic inflammatory diseases, and subclinical atheromatosis: A systematic review.

BACKGROUND AND AIMS: Systemic inflammatory diseases could act as an unfavorable condition in which epicardial adipose tissue (EAT) becomes harmful to cardiovascular health. The objectives were: (a) to quantitatively compare the presence of EAT between patients with systemic inflammatory diseases and controls; (b) to analyze the association between EAT and subclinical atheromatosis in individuals with systemic inflammatory diseases. METHODS: Studies that have quantified EAT in a population with systemic inflammatory diseases compared to a control group, or that describe the association between EAT and the presence of subclinical atheromatosis in patients with systemic inflammatory diseases were included. A quantitative analysis was performed for the first objective. This systematic review was performed according to PRISMA guidelines. RESULTS: Twenty-one studies including 1448 patients with systemic inflammatory diseases, were considered eligible for this study. Patients with systemic inflammatory disease have a higher volume (MD: 10.4cm3 [1.8-19.1]; p<0.01), higher thickness (MD: 1.0mm [0.8-1.2]; p<0.01), and a statistically non-significant higher area (MD: 3.1cm2 [1.0-5.2]; p=0.46) of EAT compared to the control group. Most studies reported a significant association between EAT and subclinical atheromatosis in patients with different systemic inflammatory diseases. CONCLUSION: This study demonstrated that EAT is increased in patients with systemic inflammatory diseases compared with healthy controls, and that EAT measurement is closely correlated with subclinical atherosclerosis in these patients. The causality of this association should be tested in prospective studies.

The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto's thyroiditis (HT) and hyperthyroidism (Graves-Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described.

Plasma Lipoprotein(a) Levels in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

INTRODUCTION: The polycystic ovary syndrome (PCOS) may represent an important model of lipid alterations. Lipoprotein(a) [Lp(a)] has emerged as a new marker of cardiovascular risk. AIM: The main objective of this meta-analysis was to analyze the available evidence on Lp(a) levels in patients with PCOS compared to a control group. METHODS: This meta-analysis was performed according to PRISMA guidelines. A literature search was performed to detect studies that have quantified Lp(a) levels in women with PCOS compared to a control group. The primary outcome was Lp(a) levels expressed in mg/dL. Random effects models were used. RESULTS: Twenty-three observational studies including 2,337 patients were identified and considered eligible for this meta-analysis. In the overall analysis, the quantitative analysis showed that patients with PCOS have a higher Lp(a) levels (SMD: 1.1 [95% CI: 0.7 to 1.4]; I2=93%) compared to the control group. The results were similar in the analysis of the subgroups of patients according to body mass index (normal weight group: SMD: 1.2 [95% CI: 0.5 to 1.9], I2=95%; overweight group: SMD: 1.2 [95% CI: 0.5 to 1.8], I2=89%). Sensitivity analysis showed that the results were robust. CONCLUSIONS: This meta-analysis shows that women with PCOS had higher levels of Lp(a) compared to healthy women used as a control group. These findings were observed in both overweight and non-overweight women.

Population Status of Vitamin B12 Values in the General Population and in Individuals with Type 2 Diabetes, in Southwestern Colombia.

Vitamin B12 (B12) is necessary for the proper functioning of the central and peripheral nervous systems. Although there is no exact definition for B12 levels, a value of 200 pg/mL is compatible with deficiency, 200-299 pg/mL is considered borderline, and 300 pg/mL is considered normal. In population studies, the prevalence of B12 deficiency ranges between 2.9% and 35%. Furthermore, many medications, such as metformin [for type 2 diabetes mellitus (T2DM)], can cause B12 deficiency. The objectives of this study were to determine the population status of B12 in southwestern Colombia (and the status of B12 in subjects with T2DM). In the total population (participants with and without T2DM), the prevalence of B12 deficiency was 17.8%; that of borderline was 19.3%; and that of normal levels was 62.9%. The prevalence of deficiency increased with age and was significantly higher in those aged ≥60 years (p = 0.000). In T2DM subjects, the prevalence of deficiency was significantly higher concerning those without T2DM (p = 0.002) and was significantly higher in those who received >1 gm/day of metformin (p = 0.001). Thus, the prevalence of deficiency and borderline levels of B12 in our population was high, particularly in those >60 years of age. B12 deficiency was significantly higher in individuals with T2DM than in individuals without T2DM, especially among those receiving high doses of metformin.

Relationship between lipoprotein(a) levels, cardiovascular outcomes and death in patients with chronic kidney disease: a systematic review of prospective studies.

INTRODUCTION AND AIM: In the general population, high levels of lipoprotein(a) (Lp(a)) are an independent risk factor for atherosclerotic cardiovascular diseases. However, the information available in patients with chronic kidney disease (CKD) is less robust. The main objective of this updated systematic review of prospective studies was to analyze the association between elevated Lp(a) levels and cardiovascular outcomes or death in patients with CKD. METHODS: The PRISMA guidelines were used to carry out this systematic review. Randomized clinical trials or prospective observational studies that evaluated the association between Lp(a) levels and cardiovascular outcomes or death in CKD patients were searched in the current literature. RESULTS: Fifteen studies including 12,260 individuals were identified and considered eligible for this systematic review. In total, 14 prospective cohorts and one post-hoc analysis of a randomized clinical trial were analyzed. Eight studies evaluated hemodialysis patients, one study analyzed patients on peritoneal dialysis, while six studies evaluated subjects with different stages of CKD. Median follow-up duration ranged from 1 to 8.6 years. Our findings showed that elevated Lp(a) values were associated with a higher risk of cardiovascular events or death in most studies, despite adjusting for traditional risk factors. CONCLUSION: The findings of this systematic review show that there is a positive association between Lp(a) levels and fatal and non-fatal cardiovascular events in patients with CKD.

Analyses of familial chylomicronemia syndrome in Pereira, Colombia 2010-2020: a cross-sectional study.

BACKGROUND AND AIM: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations in genes involved in chylomicron metabolism. On the other hand, multifactorial chylomicronemia syndrome (MCS) is a polygenic disorder and the most frequent cause of chylomicronemia, which results from the presence of multiple genetic variants related to chylomicron metabolism, in addition to secondary factors. Indeed, the genetic determinants that predispose to MCS are the presence of a heterozygous rare variant or an accumulation of several SNPs (oligo/polygenic). However, their clinical, paraclinical, and molecular features are not well established in our country. The objective of this study was to describe the development and results of a screening program for severe hypertriglyceridemia in Colombia. METHODS: A cross-sectional study was performed. All patients aged >18 years with triglyceride levels ≥500 mg/dL from 2010 to 2020 were included. The program was developed in three stages: 1. Review of electronic records and identification of suspected cases based on laboratory findings (triglyceride levels ≥500 mg/dL); 2. Identification of suspected cases based on laboratory findings that also allowed us to exclude secondary factors; 3. Patients with FCS scores <8 were excluded. The remaining patients underwent molecular analysis. RESULTS: In total, we categorized 2415 patients as suspected clinical cases with a mean age of 53 years, of which 68% corresponded to male patients. The mean triglyceride levels were 705.37 mg/dL (standard deviation [SD] 335.9 mg/dL). After applying the FCS score, 2.4% (n = 18) of patients met the probable case definition and underwent a molecular test. Additionally, 7 patients had unique variants in the APOA5 gene (c.694 T > C; p. Ser232Pro) or in the GPIHBP1 gene (c.523G > C; p. Gly175Arg), for an apparent prevalence of familial chylomicronemia in the consulting population of 0.41 per 1.000 patients with severe HTG measurement. No previously reported pathogenic variants were detected. CONCLUSION: This study describes a screening program for the detection of severe hypertriglyceridemia. Although we identified seven patients as carriers of a variant in the APOA5 gene, we diagnosed only one patient with FCS. We believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

Relationship of Subclinical Hypothyroidism on Epicardial Adipose Tissue: A Systematic Review and Meta-Analysis.

Accumulation of epicardial adipose tissue (EAT) and Subclinical hypothyroidism (SH) are associated with increased cardio-metabolic risk. The objective of this study was to quantitatively compare EAT thickening between patients with SH and healthy controls. Therefore, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases; we analyzed a group of observational studies who compare the EAT changes between SH vs control groups. A total of 9 studies were included in the final analysis, for a total of 424 patients with SH and 330 controls. Random or fixed effects models were used. Pooled analysis revealed that HS increased EAT (MD: 1.0 mm [0.40; 1.50]; P < 0.01). This meta-analysis suggests that the amount of EAT is significantly increased in SH patients. EAT might be a marker of cardiovascular risk in patients with SH.

Effect of glucagon-like peptide-1 (GLP-1) analogues on epicardial adipose tissue: A meta-analysis.

BACKGROUND AND AIMS: Glucagon-like peptide-1 (GLP-1) analogues reduce body fat and cardiovascular events in patients with type 2 diabetes. Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and coronary events in type 2 diabetes. METHODS: A systematic review and meta-analysis were performed from Glucagon-like peptide-1 analogues therapy on type 2 diabetes patients, reporting data from changes in EAT, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. RESULTS: It has been found a limited number of studies, a total of 4 studies (n = 160 patients with GLP-1 analogues therapy) were included in the final analysis. Pooled analysis revealed that GLP-1 analogues reduce EAT (MD: 1.83 mm [-2.50; -1.10]; P < 0.01). Compared with the patients before the treatment, the patients after the treatment had a smaller HbA1c (MD -1.10%[-1.80; -0.30]; p = 0.0143) and body mass index was reduced (MD -2.20 kg/m2[-3.70; -0.60]; p = 0.0058), GLP-1 therapy reduced low-density lipoprotein levels (MD-13.53 mg/dL [-21.74; -5.31]; p = 0.001) and reduced triglycerides levels significantly (MD -18.32 -28.20 mg/dL; -8.50); p = 0.0003). CONCLUSIONS: This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with Glucagon-like peptide-1 analogues.

Epicardial Adipose Tissue Ceramides Are Related to Lipoprotein Lipase Activity in Coronary Artery Disease: Unfolding a Missing Link.

BACKGROUND: Epicardial adipose tissue (EAT) contributes to coronary artery disease (CAD). EAT presents a specific lipidomic signature, showing increased ceramides and other proinflammatory lipids content. Besides, LPL (lipoprotein lipase) activity in EAT would contribute to its expansion, supplying fatty acids to the tissue. Our aim was to evaluate the relations between LPL activity, regulators of LPL, and ceramides in EAT from CAD patients. METHODS: We studied patients undergoing coronary bypass graft (CAD, n=25) and patients without CAD (no CAD, n=14). EAT and subcutaneous AT (SAT) were obtained, tissue LPL activity and its regulator's expression (ANGPTL4, GPIHBP1 [glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1], and PPARγ [peroxisomal proliferator-activated receptor γ]) were assessed. Tissue lipidomes were evaluated by UHPLC-MS, in positive and negative ionization modes. RESULTS: LPL activity was higher in EAT from CAD (P<0.001), and in EAT than SAT in both groups (P<0.001). ANGPTL4 levels were lower, GPIHBP1 and PPARγ levels were higher in EAT from CAD (P<0.001). In both groups, EAT exhibited more ceramide (P=0.01), directly associated with LPL activity, being the strongest association with Cer18:1/24:1 (P<0.001). EAT Cer18:1/16:0 to Cer18:1/24:0 and Cer18:1/24:1 to 18:1/24:0 ratios were higher in CAD (P=0.03; P<0.001, respectively), the latter directly associated with LPL activity (r=0.63, P<0.001) GPIHBP1 levels (r=0.68, P<0.001), and inversely to EAT ANGPTL4 expression (r=-0.49, P=0.03). Pairwise partial correlation network showed associations among bioactive lipids and LPL and its regulators (P<0.001 in all cases). CONCLUSIONS: The association between LPL activity, total ceramide, and the atherogenic ceramide ratios highlights the importance of the enzyme and these bioactive lipids contributing to the different metabolic profile of EAT in CAD.

Effectiveness of Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy on Lipid Levels in Type 2 Diabetes: a Meta-analysis.

INTRODUCTION: Obesity and its co-morbidities, including type 2 diabetes (T2DM) and dyslipidemia, are accompanied by excess cardiovascular morbi-mortality. Aside from excess low density lipoprotein-cholesterol (LDL-C), atherogenic dyslipidemia (AD), mainly characterized by elevated triglycerides and decreased high density lipoprotein-cholesterol (HDL-C) levels, is often present in T2DM obese patients. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), has become a reference treatment in that population. However, the respective effects of RYGB vs SG on lipid metabolism in T2DM patients have been rarely studied. METHODS: A meta-analysis of randomized controlled trials, comparing the effects of RGYBG vs SG on lipid metabolism 12 months after surgery in T2DM patients, was performed. RESULTS: Four studies including a total of 298 patients (151 patients in the RYGB and 147 patients in the SG group) were examined. Despite a greater decrease in body mass index and greater improvement in glycemic control in RYGB compared to SG. RYGB vs SG was more effective in reducing total cholesterol, LDL-C, and non-HDL-C levels (mean difference [MD] -26.10 mg/dL, 95 % CI -38.88 to -13.50, p<0.00001; [MD] -20.10 mg/dL, 95 % CI -27.90 to -12.20, p<0.00001 and MD 31.90 mg/dl, 95 % CI -46.90 to -16.80, p<0.00001, respectively). CONCLUSIONS: The superiority of RYGB vs SG in reducing LDL-C, with an effect comparable to a moderate-intensity statin, suggests RYBG should be favored in hypercholesterolemic T2DM patients in order to further reduce cardiovascular risk.

Selective effect of laparoscopic Roux-en-Y gastric bypass on lipid metabolism. / Efecto selectivo de bypass gástrico laparoscópico en Y de Roux sobre el metabolismo lipídico.

INTRODUCTION: Bariatric surgery (BS) has shown to reduce cardiovascular morbidity and mortality in obesity. The BS has improved the dyslipidemia of the insulin resistant patient, our objective was to evaluate if there was a difference in the lipid profile between the laparoscopic roux-en-Y gastric bypass (RYGB) technique vs. the sleeve gastrectomy (SG) technique at 18 months of follow-up. METHODS: An observational, open, prospective study of morbidly obese patients who underwent bariatric surgery at 18-month follow-up. Anthropometric analysis, body composition, energy expenditure at rest, glucose, insulin, HbA1c, LDL, HDL, TG and CT were performed. RESULTS: Absence baseline differences were found in the proportion of patients with hypertension, diabetes, steatosis, and sex between the RYGB vs SG groups. A reduction of TG was observed at 6 months in favor of RYGB vs SG: 108.60±34.86 vs. 124.59±44.58, P = 0.044), however, a decrease in both LDL levels was found at 12 and 18 months in favor of the RYGB vs. SG group: 96.23±24.33 vs. 107.83±28.88, P = 0.025; 90.98±20.62 vs 106.22±31.48, P = 0.003; the decrease in CT was observed only at 18 months in favor of the RYGB vs. SG group: 171.39±25.058 vs. 186.89±31.81, P = 0.005. CONCLUSIóN: RYBG has shown to be more effective in reducing LDL and CT levels compared to SG, which provides an additional benefit of RYGB in relation to the lipid profile of the patient.

Challenges in familial chylomicronemia syndrome diagnosis and management across Latin American countries: An expert panel discussion.

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by extremely high triglyceride levels due to impaired clearance of chylomicrons from plasma. This paper is the result of a panel discussion with Latin American specialists who raised the main issues on diagnosis and management of FCS in their countries. Overall FCS is diagnosed late on the course of the disease, is characterized by heterogeneity on the occurrence of pancreatitis, and remains a long time in care of different specialists until reaching a lipidologist. Pancreatitis and secondary diabetes are frequently seen, often due to late diagnosis and inadequate care. Molecular diagnosis is unusual; however, loss of function variants on the lipoprotein lipase gene are apparently the most frequent etiology. A founder effect of the glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gene has been described in the northeast of Brazil. Low awareness of the disease amongst health professionals contributes to inadequate care and an inadequate patient journey.

Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis.

(1) Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) reduce adipose tissue and cardiovascular events in patients with type 2 diabetes (T2D). Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and obstructive coronary disease events in patients with T2D. (2) We performed a systematic review and meta-analysis of SGLT2-i therapy on T2D patients, reporting data on changes in EAT after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A random effects or fixed effects model meta-analysis was then applied. (3) Results: A total of three studies (n = 64 patients with SGLT2-i, n = 62 with standard therapy) were included in the final analysis. SGLT2 inhibitors reduced EAT (SMD: -0.82 (-1.49; -0.15); p < 0.0001). An exploratory analysis showed that HbA1c was significantly reduced with SGLT2-i use, while body mass index was not significantly reduced with this drug. (4) Conclusions: This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with SGLT2-i treatment.

Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism.

BACKGROUND: Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism. OBJECTIVE: We aimed to examine the direct and/or indirect role of GH on TRL metabolism. METHODS: We investigated the effect on fasting and postprandial hepatic-TRL and intestinal-TRL metabolism of short-term (one month) withdrawal of GH in 10 GH-deficient adults. RESULTS: After GH withdrawal, we found a reduction in fasting plasma TRL concentration (significant decrease in TRL-TG, TRL-cholesterol, TRL-apoB-100, TRL-apoC-III and TRL-apoC-II) but not in postprandial TRL response. This reduction was due to fewer fasting TRL particles without a change in TG per particle and was not accompanied by a change in postprandial TRL-apoB-48 response. Individual reductions in TRL correlated strongly with increases in insulin sensitivity and decreases in TRL-apoC-III. CONCLUSION: In this relatively short term 'loss of function' human experimental model, we have shown an unanticipated reduction of hepatic-TRL particles despite increase in total body fat mass and reduction in lean mass. These findings contrast with the atherogenic dyslipidemia previously described in chronic GH deficient states, providing a new perspective for the role of GH in lipoprotein metabolism.

Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression.

BACKGROUND: Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, these studies were mostly small and their results were not always robust. The objectives were: (1) to define if a dual lipid-lowering therapy (statin + non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in low density lipoprotein cholesterol (LDL-C) and non-high-density-lipoprotein cholesterol (non-HDL-C) levels and atherosclerosis regression. METHODS: A meta-analysis including trials of non-statin lipid-lowering therapy, reporting LDL-C, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up was performed. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed. RESULTS: Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [- 4.0 mm3 (CI 95% -5.4 to - 2.6)]; I2 = 0%]. The findings were similar in the stratified analysis according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors). In the meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 1.0 mm3 and 1.1 mm3 regressions in TAV. CONCLUSION: These data suggests the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in a significant regression of TAV. Reduction of coronary atherosclerosis observed with non-statin lipid-lowering therapy is associated to the degree of LDL-C and non-HDL-C lowering. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment).

Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease.

OBJECTIVE: Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS: CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.

Impact of Lipid-Lowering Therapy on Mortality According to the Baseline Non-HDL Cholesterol Level: A Meta-Analysis.

INTRODUCTION: Previous report showed that more intensive lipid-lowering therapy was associated with less mortality when baseline LDL-C levels were > 100 mg/dL. Non-HDL-C is a better predictor of cardiovascular risk than simpler LDL-C. AIM: The objective of this meta-analysis was to define the impact of lipid-lowering therapy on the reduction of total and cardiovascular mortality by different baseline levels of non-HDL-C. METHODS: We performed a meta-analysis including randomized, controlled clinical trials of lipid-lowering therapy, reporting mortality with a minimum of 6 months of follow-up, searching in PubMed/Medline, EMBASE and Cochrane Clinical Trials databases. The random-effects model and meta-regression were performed. RESULTS: Twenty nine trials of lipid-lowering drugs, including 233,027 patients, were considered eligible for the analyses. According to the baseline non-HDL-C level, the results on cardiovascular mortality were: (1) ≥ 190 mg/dL: OR 0.63 (95% CI 0.53-0.76); (2) 160-189 mg/dL: OR 0.82 (95% CI 0.75-0.89); (3) 130-159 mg/dL: OR 0.71 (95% CI 0.52-0.98); (4) < 130 mg/dL: OR 0.95 (95% CI 0.87-1.05). When evaluating mortality from any cause, the results were the following: (1) ≥ 190 mg/dL: OR 0.70 (95% CI 0.61-0.82); (2) 160-189 mg/dL: OR 0.91 (95% CI 0.83-0.98); (3) 130-159 mg/dL; OR 0.88 (95% CI 0.77-1.00); (4) < 130 mg/dL: OR 0.98 (95% CI 0.91-1.06). The meta-regression analysis showed a significant association between baseline non-HDL-C and mortality. CONCLUSIONS: In these meta-analyses, lipid-lowering therapy was associated with reduction in the risk of all-cause and cardiovascular mortality when baseline non-HDL-C levels were above than 130 mg/dL.