Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals that promise improvement in the atheromatous plaque from a molecular point of view, because have actions on the exposure of the LDL-Receptor (LDL-R), on endothelial dysfunction, activation of macrophages, on lipid oxidation, formations on foam cells, and deposition extracellular lipids. Atheroma plaque reduction both as a result of LDL-Cholesterol (LDL-C) intensive lowering and reducing inflammation and other residual risk factors is an integral part of the management of atherosclerotic disease, and the use of valid therapeutic alternatives appear to be appealing avenues to solving the problem.

The objective was to evaluate the effects of 6 months of supplementation with Altilix^®, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix^® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix^® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (−2.40% (95% CI −3.79, −1.01); p < 0.001), waist circumference (−2.76% (95% CI −4.55, −0.96); p = 0.003), HbA1c (−0.95% (95% CI −1.22, −0.67); p < 0.001), plasma lipids, FLI (−21.83% (95% CI −27.39, −16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (−39.48% (95% CI −47.98, −30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix^® supplementation improved hepatic and cardio-metabolic parameters in MetS subjects. Altilix^® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.

Introduction: Diabetic dyslipidemia is frequent among patients with type 2 diabetes mellitus (T2DM) and is characterized by an increase in triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and small-dense (atherogenic) particles, and by a decrease in low high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 that are strongly related to insulin resistance. The increased flux of free fatty acids from adipose tissue to the liver aggravates hepatic insulin resistance and promotes all of aspects of the dyslipidemic state. Areas covered: Statins are the first-line agents for treatment while other lipid-lowering drugs (ezetimibe, fibrate and proprotein convertase subtilisin/kexin type 9) or novel anti-diabetic agents (dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon like peptide-1 receptor agonist (GLP-1RA), sodium/glucose cotransporter 2 inhibitors (SGLT2is)) or nutraceuticals (berberine, omega 3 fatty acid, red yeast rice) can be used alone or in combination. Expert Opinion: In patients with type 2 diabetes mellitus, lipid abnormalities should be identified and treated as part of the overall diabetic treatment, in order to prevent cardiovascular disease. The choice of drugs to be used is mainly based on the lipid profile and on the characteristic lipoprotein abnormalities; the use of new drugs for the treatment of hyperglycemia and lipids alteration in these patients can improve diabetic dyslipidemia.

Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix^® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix^® study in order to analyze the supplement’s effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and < 30 kg/m². All subjects received the Altilix^® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix^® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix^® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects.

Background: Metabolic syndrome is a clinical condition that deserves special attention because it puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering precision medicine, it would be advisable to evaluate the individual cardio-metabolic risk by estimating the coexistence of risk factors (abdominal obesity, low level of High-Density Lipoprotein Cholesterol, High Triglycerides, and small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could engrave on metabolism increasing cardiovascular mortality. Objective: To identify genetic and epigenetic biomarkers may assist in the possibility of helping follow-up strategies and other measures of prevention and in metabolic risk. Methods: We searched for studies that valued the combination between epigenetic biomarkers and all factors of cardio-metabolic risk. Results: Numerous researches have investigated the molecular start of metabolic alterations, focusing on the epigenetic mark, as methylation of DNA, histone modifications and non.coding RNAs. It has been found that DNA methylation is the most searched epigenetic sign in the human genome concerning the control of gene expression. Conclusion: For the screening, diagnosis, and prognosis of metabolic syndrome and the prescription of personalized medicine, the DNA methylation biomarkers specify for subjects have been recognized as an ensuring tool. While these results are promising, further investigations are needed to unravel the complicated synergic association of the genome, epigenome and the situations related to metabolic pathology.

Small, dense low-density lipoproteins (LDLs) are more susceptible to oxidation than their larger, more buoyant counterparts and therefore the biological modification of these LDL particles may, in part, be responsible for their atherogenic properties. Kotani et al. found that at multiple regression analysis there was an independent and significant inverse correlation between the mean LDL particle size and the oxidative stress status; notably, the authors adjusted not only for the traditional cardiovascular risk factors, but also for drug treatments. Higher levels of small, dense LDL concentrations significantly contribute to atherosclerosis, and lipoprotein size and subfractions may refine cardiovascular disease risk assessment.