Search Results (17)

Clinical trial results indicate that statin therapy aimed at normalising the lipid profile can prevent and reduce the risk of cardiovascular events. Both LDL and HDL consist of several subfractions, with only the smallest and densest subfractions being the most atherogenic. We examine the effect of Atorvastatin treatment not only on basic lipid profile parameters but also atherogenic lipoprotein subfractions and 25(OH)D levels in patients after the first acute myocardial infarction. The study population had not previously received lipid-lowering medications. Serum 25(OH)D concentration was determined by direct competitive immunochemiluminescent assays. Lipoprotein subfractions, including VLDL, IDL-C, IDL-B, and IDL-A, as well as LDL1, LDL2 (large LDL), and LDL3-7 (sdLDL), were measured in serum (Lipoprint^® system). Almost all patients had 25(OH)D deficiency. Atorvastatin primarily reduced strongly atherogenic sdLDL and decreased the less atherogenic large LDL subfractions. A statistically significant reduction in VLDL cholesterol and IDL fractions was also observed. Analysing LDL subfractions provides a more detailed insight into lipid metabolism and enables the identification of patients with a more atherogenic phenotype. LDL subfractions may thus become not only more accurate prognostic biomarkers but also targets for lipid-lowering therapy. Vitamin D deficiency is associated with atherogenic dyslipidaemia, particularly high levels of sdLDL. Full article

Affecting approximately 25% of the global population, steatotic liver disease (SLD) poses a significant health concern. SLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis and fibrosis with a risk of severe liver complications such as cirrhosis and hepatocellular carcinoma. SLD is associated with obesity, atherogenic dyslipidaemia, and insulin resistance, increasing cardiovascular risks. As such, identifying SLD is vital for cardiovascular disease (CVD) prevention and treatment. Bile acids (BAs) have critical roles in lipid digestion and are signalling molecules regulating glucose and lipid metabolism and influencing gut microbiota balance. BAs have been identified as critical mediators in cardiovascular health, influencing vascular tone, cholesterol homeostasis, and inflammatory responses. The cardio-protective or harmful effects of BAs depend on their concentration and composition in circulation. The effects of certain BAs occur through the activation of a group of receptors, which reduce atherosclerosis and modulate cardiac functions. Thus, manipulating BA receptors could offer new avenues for treating not only liver diseases but also CVDs linked to metabolic dysfunctions. In conclusion, this review discusses the intricate interplay between BAs, metabolic pathways, and hepatic and extrahepatic diseases. We also highlight the necessity for further research to improve our understanding of how modifying BA characteristics affects or ameliorates disease. Full article

(1) Background: Dyslipidaemia and insulin resistance are major risk factors for coronary artery disease (CAD). This study investigated the relationship between plasma atherogenic index (PA-I), triglyceride-glucose index (TGI) and other lipid ratios with the presence and prediction of CAD among different age categories. (2) Methods: The study included 223 participants diagnosed with CAD and those with normal coronary arteries (normal group) by coronary computed tomography angiography (CCTA). Participants were categorised by age and sex: premature CAD (PCAD) for men under 55 and women under 65, and older groups as elderly. (3) Results: PA-I, Lipid Combined Index, Castelli Risk Indices, and TGI were significantly higher in the PCAD group compared to the control group (p < 0.05). ROC analysis showed that a PA-I cut-off of 0.41 had a sensitivity of 62% and a specificity of 58% for predicting PCAD, while a TGI cut-off of 8.74 had a sensitivity of 68% and a specificity of 62%. In the elderly, no significant differences in these indices were found between the CAD and normal groups. (4) Conclusions: Traditional lipid profiles and non-traditional lipid indices such as PA-I and TGI show significant differences in predicting CAD in younger populations but not in older groups. TGI and PA-I may be promising biomarkers for the prediction of PAD, although further validation is needed. Full article

Metabolic syndrome (MetS) is a significant health problem. The co-occurrence of obesity, carbohydrate metabolism disorders, hypertension and atherogenic dyslipidaemia is estimated to affect 20–30% of adults worldwide. Researchers are seeking solutions to prevent and treat the conditions related to MetS. Preventive medicine, which focuses on modifiable cardiovascular risk factors, including diet, plays a special role. A diet rich in fruits and vegetables has documented health benefits, mainly due to the polyphenolic compounds it contains. Anthocyanins represent a major group of polyphenols; they exhibit anti-atherosclerotic, antihypertensive, antithrombotic, anti-inflammatory and anticancer activities, as well as beneficial effects on endothelial function and oxidative stress. This review presents recent reports on the mechanisms involved in the protective effects of anthocyanins on the body, especially among people with MetS. It includes epidemiological data, in vivo and in vitro preclinical studies and clinical observational studies. Anthocyanins are effective, widely available compounds that can be used in both the prevention and treatment of MetS and its complications. Increased consumption of anthocyanin-rich foods may contribute to the maintenance of normal body weight and modulation of the lipid profile in adults. However, further investigation is needed to confirm the beneficial effects of anthocyanins on serum glucose levels, improvement in insulin sensitivity and reduction in systolic and diastolic blood pressure. Full article

Dyslipidaemia is a modifiable risk factor commonly associated with diabetes mellitus and prediabetes, with a major impact on the early development of atherosclerotic cardiovascular disease. Various studies have tried to identify the key treatment targets, their optimal values according to patients’ CV risk, and the most efficient yet safe therapeutic agents which, alongside lifestyle changes, would improve lipid levels and reduce cardiovascular mortality and morbidity. Currently, there are multiple pharmacologic options that can be used in the management of dyslipidaemia, such as statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, n-3 polyunsaturated fatty acids or fibrates, to name only a few, while many other are under development. In the current setting of a continuously increasing population of patients with metabolic disorders, this review aims to summarise current knowledge regarding lipid disorders and the recommendations of recent guidelines in treating dyslipidaemia in patients with diabetes mellitus or prediabetes. Full article

Metabolic syndrome (MS) is a growing disorder affecting thousands of people worldwide, especially in industrialised countries, increasing mortality. Oxidative stress, hyperglycaemia, insulin resistance, inflammation, dysbiosis, abdominal obesity, atherogenic dyslipidaemia and hypertension are important factors linked to MS clusters of different pathologies, such as diabesity, cardiovascular diseases and neurological disorders. All biochemical changes observed in MS, such as dysregulation in the glucose and lipid metabolism, immune response, endothelial cell function and intestinal microbiota, promote pathological bridges between metabolic syndrome, diabesity and cardiovascular and neurodegenerative disorders. This review aims to summarise metabolic syndrome’s involvement in diabesity and highlight the link between MS and cardiovascular and neurological diseases. A better understanding of MS could promote a novel strategic approach to reduce MS comorbidities. Full article

Background: Atherogenic dyslipidaemia (AD) and lipid triad (LT) are characterised by high triglyceride levels together with low HDL and normal or high LDL cholesterol and are favoured by a persistent state of insulin resistance (IR), which increases the release of free fatty acids from abdominal adipose tissue. This alteration in the lipid profile favours the accelerated development of atherosclerosis, which is the most important cause of morbidity and mortality in all countries in the developed and developing world. One of the elements that plays a major role in the genesis of AD is IR. The aim of this study was to determine the relationship between variables that assess atherogenic risk (AD and LT) and scales that assess the risk of presenting insulin resistance. Methods: A descriptive cross-sectional study of 418,343 workers was conducted to evaluate atherogenic dyslipidaemia and lipid triad; a relationship with three insulin resistance risk scales (Triglycerides/HDL, TyG index, METS-IR) was established. The usefulness of IR risk scales for predicting AD and LT was calculated by applying ROC curves, obtaining the area under the curve (AUC) and cut-off points with their sensitivity, specificity, and Youden index. Multivariate analysis was performed by binary logistic regression. Results: The prevalence of high-risk values for insulin resistance with all of the scales is much higher in people with AD and LT compared to those without. The ROC curves present us with an AUC with the three insulin resistance risk scales for the two dyslipidaemias studied with figures ranging between 0.856 and 0.991, which implies that the results are good/very good. Conclusions: A relationship between atherogenic dyslipidaemia and the three insulin resistance risk scales assessed is revealed, with higher IR mean values and prevalence in people with atherogenic dyslipidaemia and lipid triad. The three scales make it possible to adequately classify the presence of AD and LT. The highest AUC is presented by the triglycerides/HDL scale, with a result close to 1. METS-IR is the most recommended formula to estimate insulin resistance. Full article

Obstructive sleep apnoea (OSA) is associated with cardiovascular and metabolic comorbidities, including hypertension, dyslipidaemia, insulin resistance and atherosclerosis. Strong evidence suggests that OSA is associated with an altered lipid profile including elevated levels of triglyceride-rich lipoproteins and decreased levels of high-density lipoprotein (HDL). Intermittent hypoxia; sleep fragmentation; and consequential surges in the sympathetic activity, enhanced oxidative stress and systemic inflammation are the postulated mechanisms leading to metabolic alterations in OSA. Although the exact mechanisms of OSA-associated dyslipidaemia have not been fully elucidated, three main points have been found to be impaired: activated lipolysis in the adipose tissue, decreased lipid clearance from the circulation and accelerated de novo lipid synthesis. This is further complicated by the oxidisation of atherogenic lipoproteins, adipose tissue dysfunction, hormonal changes, and the reduced function of HDL particles in OSA. In this comprehensive review, we summarise and critically evaluate the current evidence about the possible mechanisms involved in OSA-associated dyslipidaemia. Full article

Dyslipidaemia leads to proatherogenic oxidative lipid stress that promotes vascular inflammation and thrombosis, the pathologies that underpin myocardial infarction, stroke, and deep vein thrombosis. These prothrombotic states are driven, at least in part, by platelet hyperactivity, and they are concurrent with the appearancxe of oxidatively modified low-density lipoproteins (LDL) in the circulation. Modified LDL are heterogenous in nature but, in a general sense, constitute a prototype circulating transporter for a plethora of oxidised lipid epitopes that act as danger-associated molecular patterns. It is well-established that oxidatively modified LDL promote platelet activation and arterial thrombosis through a number of constitutively expressed scavenger receptors, which transduce atherogenic lipid stress to a complex array of proactivatory signalling pathways in the platelets. Stimulation of these signalling events underlie the ability of modified LDL to induce platelet activation and blunt platelet inhibitory pathways, as well as promote platelet-mediated coagulation. Accumulating evidence from patients at risk of arterial thrombosis and experimental animal models of disease suggest that oxidised LDL represents a tangible link between the dyslipidaemic environment and increased platelet activation. The aim of this review is to summarise recent advances in our understanding of the pro-thrombotic signalling events induced in platelets by modified LDL ligation, describe the contribution of individual platelet scavenger receptors, and highlight potential future challenges of targeting these pathways. Full article

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis. Full article

Cardiovascular disease (CVD) is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE) associated with atherosclerosis. The interplay between dyslipidaemia and inflammation—mechanisms that drive atherosclerosis—were investigated retrospectively in adolescent JSLE patients using lipoprotein-based serum metabolomics in patients with active and inactive disease, compared to healthy controls (HCs). Data was analysed using machine learning, logistic regression, and linear regression. Dyslipidaemia in JSLE patients was characterised by lower levels of small atheroprotective high-density lipoprotein subsets compared to HCs. These changes were exacerbated by active disease and additionally associated with significantly higher atherogenic very-low-density lipoproteins (VLDL) compared to patients with low disease activity. Atherogenic lipoprotein subset expression correlated positively with clinical and serological markers of JSLE disease activity/inflammation and was associated with disturbed liver function, and elevated expression of T-cell and B-cell lipid rafts (cell signalling platforms mediating immune cell activation). Finally, exposing VLDL/LDL from patients with active disease to HC lymphocytes induced a significant increase in lymphocyte lipid raft activation compared to VLDL/LDL from inactive patients. Thus, metabolomic analysis identified complex patterns of atherogenic dyslipidaemia in JSLE patients associated with inflammation. This could inform lipid-targeted therapies in JSLE to improve cardiovascular outcomes. Full article

Cardiovascular disease (CVD) is the leading cause of death in Type 1 Diabetes (T1D). The molecular basis for atherosclerosis in T1D is heavily influenced by hyperglycaemia and its atherogenic effects on LDL. Ongoing research into the distinct pathophysiology of atherosclerosis in T1D offers exciting opportunities for novel approaches to calculate CVD risk in patients with T1D and to manage this risk appropriately. Currently, despite the increased risk of CVD in the T1D population, there are few tools available for estimating the risk of CVD in younger patients. This poses significant challenges for clinicians in selecting which patients might benefit from lipid-lowering therapies over the long term. The current best practice guidance for the management of dyslipidaemia in T1D is generally based on evidence from patients with T2D and the opinion of experts in the field. In this review article, we explore the unique pathophysiology of atherosclerosis in T1D, with a specific focus on hyperglycaemia-induced damage and atherogenic LDL modifications. We also discuss the current clinical situation of managing these patients across paediatric and adult populations, focusing on the difficulties posed by a lack of strong evidence and various barriers to treatment. Full article

Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pathways were upregulated in the MUO group. Among these miRNAs, hsa-miR-6796-5p and hsa-miR-4697-3p, which regulate oxidative stress, showed significant correlations with glucose, triglycerides, HbA1c and HDLc. Our results provide evidence of a pattern of differentially expressed miRNAs in obesity according to MetS, and identify those related to insulin resistance and lipid metabolism pathways. Full article

Background: Dyslipidaemia is well recognised in obstructive sleep apnoea (OSA) and could contribute to the development of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) predicts cardiovascular morbidity and mortality better than the individual lipid levels. The aim of this study was to investigate the AIP in patients with OSA in relation with disease severity. Methods: Four hundred sixty-one patients with OSA and 99 controls participated in this study. AIP was assessed in the morning following a diagnostic sleep study. The association between lipid values and OSA were adjusted for age, gender, and body mass index. Results: Patients with OSA had higher AIP and triglyceride, and lower high-density lipoprotein cholesterol (HDL-C) levels (all p < 0.05). AIP significantly correlated with the Epworth Sleepiness Scale score (ρ = 0.19), the apnoea-hypopnoea index (ρ = 0.40) and oxygen desaturation index (ρ = 0.43, all p < 0.05). However, there was no relationship between the AIP and markers of sleep quality such as total sleep time, sleep period time, sleep efficiency, arousal index or percentage of REM sleep (all p > 0.05). AIP was not a better predictor for self-reported cardiovascular disease or diabetes than HDL-C. Conclusions: AIP is elevated in OSA and is related to disease severity. However, it does not seem to have an additional clinical value compared to HDL-C. Full article

Non-alcoholic fatty liver disease (NAFLD) is characterized by an atherogenic dyslipidaemia and an increased cardiovascular risk. Remnant lipoprotein cholesterol (RLP-C) is emerging as a novel cardiovascular risk factor, but its predictive value in patients with NAFLD is unknown. We investigated factors affecting RLP-C levels, and the association with major adverse cardiovascular and cerebrovascular events (MACCE) in NAFLD. A prospective observational cohort study was carried out including 798 unselected patients with cardio-metabolic diseases screened by ultrasound for the presence of NAFLD. Fasting RLP-C (mg/dL) was calculated as total cholesterol—(HDL (high-density lipoprotein) + LDL (low-density-lipoprotein)). Primary endpoint of the follow-up study was a combined endpoint of MACCE. Patients with NAFLD (79.2%) had higher median fasting RLP-C in comparison to those without (27.0 vs. 20.0 mg/dL, respectively p < 0.001). Metabolic syndrome, NAFLD, age above median, and female sex were independently associated to fasting RLP-C above the median. In patients with NAFLD, values of RLP-C were associated with liver disease severity, as shown by the increasing value of RLP-C across tertiles of aspartate aminotransferase (AST) (p = 0.002) and gamma-glutamyl transpeptidase (GGT) (p < 0.001). Furthermore, levels of RLP-C and Hamaguchi score, were significantly correlated (r = 0.193, p < 0.001). During a median follow-up of 32 months (interquartile range: 14.2–51.7, 1700 person-years), 41 MACCE (2.41%/year) were registered in 596 NAFLD patients. The rate of events was higher in NAFLD patients with RLP-C above the median compared to those below (log-rank test p = 0.040). Age (hazard ratio (HR) 1.039, 95% confidence interval (CI), 1.005–1.074, p = 0.024), previous cardiovascular events (HR 2.210, 95% CI, 1.052–4.643, p = 0.036), female sex (HR 0.454, 95% CI, 0.208–0.989, p = 0.047) and RLP-C above the median (HR 2.202, 95% CI, 1.132–4.285, p = 0.020) were associated with MACCE. In conclusion, we found that NAFLD was independently associated with higher circulating RLP-C, and that high RLP-C levels were predictive of MACCE in patients with NAFLD. Full article