The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients\' quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.

OBJECTIVE: This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults.
METHODS: A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways.
RESULTS: The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein.
CONCLUSIONS: This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

Atherogenic dyslipidemia plays a critical role in the development of metabolic syndrome (MetS), being one of its major components, along with central obesity, insulin resistance, and hypertension. In recent years, the development of molecular genetics techniques and extended analysis at the genome or exome level has led to important progress in the identification of genetic factors (heritability) involved in lipid metabolism disorders associated with MetS. In this review, we have proposed to present the current knowledge related to the genetic etiology of atherogenic dyslipidemia, but also possible challenges for future studies. Data from the literature provided by candidate gene-based association studies or extended studies, such as genome-wide association studies (GWAS) and whole exome sequencing (WES,) have revealed that atherogenic dyslipidemia presents a marked genetic heterogeneity (monogenic or complex, multifactorial). Despite sustained efforts, many of the genetic factors still remain unidentified (missing heritability). In the future, the identification of new genes and the molecular mechanisms by which they intervene in lipid disorders will allow the development of innovative therapies that act on specific targets. In addition, the use of polygenic risk scores (PRS) or specific biomarkers to identify individuals at increased risk of atherogenic dyslipidemia and/or other components of MetS will allow effective preventive measures and personalized therapy.

Introduction: Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced a search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease; it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndromes, which include, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) at improving lipid profile parameters upon a 1-year follow up. Material and Methods: Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as the lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in a 1-year observation were analyzed. Results: Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL level decreases were observed along with an increase in high-density lipoprotein (HDL) cholesterol levels. Conclusions: Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

Innovative lipid-modifying agents are valuable resources to improve the control of atherogenic dyslipidemias and reduce the lipid-related residual cardiovascular risk of patients with intolerance or who are not fully responsive to a consolidated standard of care (statins plus ezetimibe). Moreover, some of the upcoming compounds potently affect lipid targets that are thus far considered \"unmodifiable\". The present paper is a viewpoint aimed at presenting the incremental metabolic and cardiovascular benefits of the emerging lipid-modulating agents and real-life barriers, hindering their prescription by physicians and their assumption by patients, which need to be worked out for a more diffuse and appropriate drug utilization.

OBJECTIVE: This study aimed to investigate the association between a combination of elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels and target lesion revascularization (TLR) following everolimus-eluting stent (EES) implantation. The adverse impact of clinical, lesion, and procedural characteristics on TLR in patients with elevated TG and reduced HDL-C levels was also assessed.
METHODS: We retrospectively collected data on 3,014 lesions from 2,022 consecutive patients, who underwent EES implantation at Koto Memorial Hospital. Atherogenic dyslipidemia (AD) is defined as a combination of non-fasting serum TG ≥ 175 mg/dL and HDL-C ＜40 mg/dL.
RESULTS: AD was observed in 212 lesions in 139 (6.9%) patients. The cumulative incidence of clinically driven TLR was significantly higher in patients with AD than in those without AD (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.43-3.73, P=0.0006). Subgroup analysis showed that AD increased the risk of TLR with the implantation of small stents (≤ 2.75 mm). Multivariable Cox regression analysis showed that AD was an independent predictor of TLR in the small EES stratum (adjusted HR 3.00, 95% CI 1.53-5.93, P=0.004), whereas the incidence of TLR was similar in the non-small-EES stratum, irrespective of the presence or absence of AD.
CONCLUSIONS: Patients with AD had a higher risk of TLR after EES implantation, and this risk was greater for lesions treated with small stents.

Combined dyslipidemia (CD), the predominant abnormal lipid pattern in children and adolescents, is characterized by moderate/severe triglyceride elevation with reduced high-density lipoprotein cholesterol. CD is prevalent, present in 30-50% of obese adolescents. Epidemiologic and lipid sub-population findings demonstrate CD to be highly atherogenic. In the short term, CD responds well to lifestyle change; long-term results are lacking.
Major longitudinal studies now confirm that CD in childhood predicts early cardiovascular disease events in adults. Targeted nutritional interventions can be safely and effectively introduced in young children. These findings support introduction of a new approach to CD management. New evidence supporting the atherosclerotic risk associated with CD and the effectiveness of lifelong diet interventions is reviewed and a new family-based primordial approach to CD beginning in infancy is proposed. Aligned with existing pediatric care recommendations, this has the potential to significantly decrease the development of CD.

BACKGROUND: In normal circumstances, AT secretes anti-inflammatory adipokines (AAKs) which regulates lipid metabolism, insulin sensitivity, vascular hemostasis, and angiogenesis. However, during obesity AT dysfunction occurs and leads to microvascular imbalance and secretes several pro-inflammatory adipokines (PAKs), thereby favoring atherogenic dyslipidemia and insulin resistance. Literature suggests decreased levels of circulating AAKs and increased levels of PAKs in obesity-linked disorders. Importantly, AAKs have been reported to play a vital role in obesity-linked metabolic disorders mainly insulin resistance, type-2 diabetes mellitus and coronary heart diseases. Interestingly, AAKs counteract the microvascular imbalance in AT and exert cardioprotection via several signaling pathways such as PI3-AKT/PKB pathway. Although literature reviews have presented a number of investigations detailing specific pathways involved in obesity-linked disorders, literature concerning AT dysfunction and AAKs remains sketchy. In view of the above, in the present contribution an effort has been made to provide an insight on the AT dysfunction and role of AAKs in modulating the obesity and obesity-linked atherogenesis and insulin resistance.
METHODS: \"Obesity-linked insulin resistance\", \"obesity-linked cardiometabolic disease\", \"anti-inflammatory adipokines\", \"pro-inflammatory adipokines\", \"adipose tissue dysfunction\" and \"obesity-linked microvascular dysfunction\" are the keywords used for searching article. Google scholar, Google, Pubmed and Scopus were used as search engines for the articles.
CONCLUSIONS: This review offers an overview on the pathophysiology of obesity, management of obesity-linked disorders, and areas in need of attention such as novel therapeutic adipokines and their possible future perspectives as therapeutic agents.

Arterial stiffness is a recognized predictor of cardiovascular morbidity and death. It is an early indicator of arteriosclerosis and is influenced by numerous risk factors and biological processes. The lipid metabolism is crucial and standard blood lipids, non-conventional lipid markers and lipid ratios are associated with arterial stiffness. The objective of this review was to determine which lipid metabolism marker has a greater correlation with vascular aging and arterial stiffness. Triglycerides (TG) are the standard blood lipids that have the strongest associations with arterial stiffness, and are often linked to the early stages of cardiovascular diseases, particularly in patients with low LDL-C levels. Studies often show that lipid ratios perform better overall than any of the individual variables used alone. The relation between arterial stiffness and TG/HDL-C has the strongest evidence. It is the lipid profile of atherogenic dyslipidemia that is found in several chronic cardio-metabolic disorders, and is considered one of the main causes of lipid-dependent residual risk, regardless of LDL-C concentration. Recently, the use of alternative lipid parameters has also been increasing. Both non-HDL and ApoB are very well correlated with arterial stiffness. Remnant cholesterol is also a promising alternative lipid parameter. The findings of this review suggest that the main focus should be on blood lipids and arterial stiffness, especially in individuals with cardio-metabolic disorders and residual cardiovascular risk.

Treatment with mirtazapine, a widely prescribed antidepressant, has been linked to weight gain and dyslipidemia. Whether dyslipidemia occurs secondary to increased appetite due to antidepressant treatment, or due to direct pharmacological effects of mirtazapine is unknown. The aim of this analysis is to complement our previously published results of the effect of mirtazapine on metabolism and energy substrate partitioning from a proof-of-concept, open-label clinical study (ClinicalTrials.gov NCT00878540) in 12 healthy males (20-25 years). We report the effect of a seven-day administration of mirtazapine 30 mg per day on weight and lipid metabolism in healthy men under highly standardized conditions with respect to diet, physical activity and day-night-rhythm and under continuous clinical observation. After a 7-day administration of mirtazapine 30 mg, we observed a statistically significant increase in triglyceride levels (mean change + 4.4 mg/dl; 95% CI [- 11.4; 2.6]; p = 0.044) as well as TG/HDL-C ratio (mean change + 0.2; 95% CI [- 0.4; 0.1]; p = 0.019) and a decrease in HDL-cholesterol (mean change - 4.3 mg/dl; 95% CI [2.1; 6.5]; p = 0.004), LDL-cholesterol (mean change - 8.7 mg/dl; 95% CI [3.8; 13.5]; p = 0.008), total cholesterol (mean change - 12.3 mg/dl; 95% CI [5.4; 19.1]; p = 0.005), and non-HDL-C (mean change - 8.0 mg/dl; 95% CI [1.9; 14.0]; p = 0.023). Notably, weight (mean change - 0.6 kg; 95% CI [0.4; 0.8]; p = 0.002) and BMI (mean change - 0.2; 95% CI [0.1; 0.2]; p = 0.002) significantly decreased. No change in waist circumference (mean change - 0.4 cm; 95% CI [- 2.1; 2.9]; p = 0.838) or waist-to-hip-ratio (mean change 0.0; 95% CI [- 0.0; 0.0]; p = 0.814) was observed. This is the first study showing unfavorable changes in lipid metabolism under mirtazapine in healthy individuals despite highly standardized conditions including dietary restriction, and despite the observation of a decrease of weight. Our findings support the hypothesis that mirtazapine has direct pharmacological effects on lipid metabolism. ClinicalTrials.gov: NCT00878540.