Search Results (287)

Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV and the underlying molecular mechanisms remain poorly understood. The objective of this study therefore was to investigate the impact of RSV on key atherosclerosis-associated processes in monocytes, macrophages, endothelial cells, and smooth muscle cells in vitro, as well as in LDL receptor-deficient mice fed a high-fat diet in vivo. RSV produced beneficial changes in the plasma lipid profile and peripheral blood lymphoid cells in vivo. RSV also attenuated plaque inflammation by decreasing macrophage and T cell content and enhanced markers of plaque stability, with increased levels of smooth muscle cells and collagen content. In vitro, RSV inhibited chemokine-driven monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion. RNA-sequencing of the thoracic aorta revealed key genes and pathways mediating the antioxidant, anti-inflammatory and plaque-stabilising activities of RSV. These studies provide novel mechanistic insights on the anti-atherogenic actions of RSV and support further evaluation in human clinical trials. Full article

Low-density lipoprotein cholesterol (LDL-C) has traditionally been the primary biomarker used to assess cardiovascular risk. However, a substantial proportion of cardiovascular events occur in individuals with LDL-C levels within the normal range, highlighting the need for additional risk markers. Lipoprotein(a) [Lp(a)] has emerged as an independent and genetically determined cardiovascular risk factor that is not adequately captured by conventional lipid profiling. Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease, including coronary artery disease, ischemic stroke, and calcific aortic valve stenosis, and appear to be particularly relevant in the context of premature cardiovascular events. The pathogenicity of Lp(a) is driven by distinct mechanisms that extend beyond cholesterol transport. These include pro-atherogenic, pro-inflammatory, and pro-thrombotic effects mediated largely by oxidized phospholipids carried by the particle and by the structural properties of apolipoprotein(a), which interfere with fibrinolysis. Despite its strong and stable genetic determination, Lp(a) remains underrecognized and inconsistently measured in clinical practice, partly due to historical limitations in assay standardization and reporting. This minireview summarizes current knowledge on the pathophysiological mechanisms underlying elevated Lp(a), discusses its clinical implications for cardiovascular risk assessment, and highlights the importance of standardized Lp(a) measurement in routine practice, particularly in light of emerging Lp(a)-targeted therapies. Full article

Background/Objectives: Ankylosing Spondylitis (AS) is associated with increased cardiovascular disease risk due to chronic systemic inflammation. The Atherogenic Index of Plasma (AIP) and Systematic Coronary Risk Evaluation (SCORE) are valuable tools for cardiovascular risk assessment, while Klotho, an anti-aging protein with cardioprotective properties, may serve as a potential biomarker for cardiovascular health. Recent studies have shown that soluble α-Klotho contributes to vascular protection by increasing endothelial cell proliferation, reducing apoptosis, and enhancing angiogenic capacity, thereby helping to maintain microvascular integrity. We aimed to assess cardiovascular event risk in AS patients using AIP and SCORE and investigate the relationship between serum Klotho levels and these factors. Methods: A case–control study was conducted between August and September 2019. The study included 24 AS patients and 24 healthy controls aged 18 and above, with 13 females and 11 males. Results: No significant difference was found in serum Klotho levels between the AS and control groups in terms of SCORE and AI classifications. In the high-risk SCORE classification group, AI was found to be elevated at 0.42. In the AS group, Klotho levels were observed as 0.73 in the low-risk group, 0.60 in the moderate-risk group, and 0.61 in the high-risk group (p = 0.974). When evaluating HDL levels, Klotho was determined to be 7.29 ± 6.81 for HDL < 35 and 0.60 [0.33] for HDL ≥ 35 (p = 0.036). Conclusions: An AI exceeding 0.40 in the high-risk SCORE group and in patients with active disease according to the BASDAI score indicated an increased cardiovascular event risk in the AS group. Further studies are warranted regarding serum Klotho levels, HDL, and LDL subclasses in AS patients. Full article

Chronic hyperglycemia inflicts serious cellular damage by inducing oxidative stress through the excessive production of free radicals. This oxidative milieu may impair the cellular redox capacity and disrupt the insulin-like growth factor (IGF) system, thereby increasing the risk of cardiovascular complications. This study aimed to investigate plasma levels of components of the IGF system and antioxidant biomarkers in young adults with type 1 diabetes mellitus (T1DM) compared to age-matched healthy controls in Brazil. This study included 129 patients with T1DM (76 female, 53 male; mean age 26.97 ± 0.6 years) and 95 healthy controls (61 female, 34 male; mean age 27.35 ± 0.68 years). Young Brazilian adults with T1DM had significantly lower mean IGF-I and higher mean IGFBP-1 levels compared to healthy controls. The T1DM group showed a more atherogenic profile, characterized by a significantly elevated ApoB/ApoA1 ratio and increased oxidized LDL levels. However, a subset of patients with significantly better glycemic control exhibited serum IGF-I and IGFBP-1 levels within the normal range observed in controls, which may indicate the presence of residual functional beta-cell activity or reflect better glycemic control in this subgroup. Antioxidant components and oxidative stress biomarkers were significantly upregulated in the T1DM group compared to the control group, suggesting a compensatory adaptive response. No significant correlation was observed between biomarkers of oxidative stress and the IGF-system. Full article

Background/Objectives: Obesity is a major risk factor for cardiovascular disease (CVD), but traditional risk calculators such as Systematic COronary Risk Evaluation (SCORE2) may not fully capture the elevated risks in individuals with obesity, especially when metabolic health is considered. This study aimed to evaluate the effectiveness of QRESEARCH risk estimator version 3 (QRISK3) in estimating 10-year cardiovascular risk in individuals with varying obesity phenotypes compared to SCORE2. Methods: A total of 88 participants (25 men, 63 women; mean age 37.4 ± 11.8 years) were categorized into four obesity phenotypes according to metabolic and anthropometric criteria. The 10-year CVD risk was calculated using SCORE2 and QRISK3 algorithms. Functional cardiovascular assessment included blood pressure (BP) measurement and electrocardiogram (ECG) interpretation for conduction abnormalities and left ventricular hypertrophy (LVH). Biochemical analysis included carbohydrate metabolism (fasting glucose, postprandial glucose, HbA1c) and lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides, atherogenic index). Results: SCORE2 underestimated CVD risk (3–8%), whereas QRISK3 predicted higher values (6–16%), particularly in metabolically unhealthy phenotypes. LVH occurred in 26–45% of participants, with elevated BP and early subclinical ECG changes even in metabolically healthy obesity individuals. Carbohydrate metabolism disturbances were observed in metabolically unhealthy participants with normal or elevated BMI, while lipid abnormalities—including elevated total cholesterol, LDL-C, triglycerides, and atherogenic index—were prominent in these metabolically unhealthy phenotypes. Insulin resistance, assessed via the triglyceride–glucose index, exceeded reference ranges in all obesity phenotypes, with the highest values seen in metabolically unhealthy individuals. Conclusions: QRISK3 provides a more precise and thorough assessment of 10-year cardiovascular risk in individuals with obesity than SCORE2. These findings highlight the importance of incorporating anthropometric and metabolic data into cardiovascular risk assessments and support the clinical use of QRISK3 for more personalized risk stratification, especially in populations with obesity and metabolic disturbances. Early identification of high-risk individuals using QRISK3 could lead to more timely and targeted preventive interventions, improving long-term cardiovascular outcomes. Full article

Background/Objectives: Coronary artery disease (CAD) remains the leading cause of death primarily in patients over 65 years old, with an increasing incidence, especially in Eastern European countries. Primary and secondary prevention protocols are based on a large number of cardiovascular (CV) risk factors, but low-density lipoprotein cholesterol (LDL-C) remains the main treatment target and one of the central determinants of CV risk. Apolipoprotein B (apoB) is the main structural protein in all atherogenic lipoproteins, and, unlike LDL-C, which only reflects the cholesterol content of LDL, apoB directly quantifies the total number of all circulating atherogenic particles. Over the past decade, a growing amount of data has supported the utility of apoB for CV risk assessment; however, its superiority over LDL-C remains unclear. Our study aimed to investigate the predictive value of apoB for both the presence and the severity of CAD in a statin-treated cohort from an Eastern European hospital and to compare it with standard lipid biomarkers. Methods: A total of 121 statin-treated patients, who were evaluated using coronary angiography, were consecutively enrolled and subdivided into three groups: 52 patients with significant coronary artery disease (S-CAD), 36 patients with non-significant coronary artery disease (NS-CAD), and 33 patients without coronary atherosclerosis (N-CAD). Apolipoprotein B was measured at the moment of enrollment using the immunoturbidimetric assay. Results: The mean values of LDL-C, TC, non-HDL-C, and apoB increased progressively across the three studied groups. Unlike traditional lipid biomarkers, apoB levels differed significantly not only between N-CAD and S-CAD, but also between N-CAD and NS-CAD. The diagnostic superiority of apoB extended beyond group mean differences, as it also demonstrated the strongest correlation with CAD severity. ApoB showed a moderate correlation with the Gensini score (r = 0.43, p < 0.001), which was markedly higher compared to LDL-C, TC, or non-HDL-C, all of which presented only a weak correlation (r = 0.26, r = 0.23, and r = 0.28, respectively). Additionally, in a logistic regression analysis, apoB demonstrated the highest predictive power for the presence of significant CAD (per SD increase: OR 2.386, 95% CI 1.52–3.75, p = 0.000), and it was the only biomarker able to predict left main disease (per SD increase: OR 2.433, 95% CI 1.38–4.30, p = 0.002) and three vessel disease (per SD increase: OR 1.639, 95% CI 1.012–2.654, p = 0.044). Residual apoB was also calculated and remained significantly associated with the presence of coronary atherosclerosis. Conclusions: ApoB proved to be a reliable predictor for CAD, independent of LDL-C. Compared to standard lipid biomarkers, apoB was superior in detecting NS-CAD and showed a better correlation with the severity of CAD. Additionally, in our study, only apoB was significantly correlated with left main disease and three vessel disease. Full article

Background/Objectives: Carnosine and exercise independently improve metabolic health, yet their combined effects on myokines and microbiota-derived metabolites remain underexplored. This study evaluated the synergistic impact of carnosine supplementation and exercise intensity on microbiota-derived metabolites, as well as skeletal muscle and myocardial expression of irisin and myonectin, focusing on lipid and glycemic regulation. Methods: A randomized post-test control study was conducted using 49 male Sprague Dawley rats (9 weeks old; 250.39 ± 1.85 g), divided into 7 groups: control (C), sham (S), moderate-intensity continuous training (MICT), high-intensity continuous training (HICT), carnosine (CA), MICT with carnosine (MICT_CA), and HICT with carnosine (HICT_CA). Interventions included treadmill-based moderate or high-intensity training and carnosine supplementation (100 mg/kg/day) for 5 weeks. Blood samples were collected post-decapitation; plasma was analyzed for lipid profile, glycemic parameters, and microbiota-derived metabolites using enzymatic and ELISA methods. Irisin and myonectin levels were assessed in plasma and myocardial and skeletal muscle tissues via ELISA and immunohistochemistry. Results: The HICT_CA group showed the lowest body weight, highest HDL-C, and lowest LDL-C, TC, TG, and atherogenic index. Irisin and myonectin levels in skeletal muscle and myocardium were also highest in HICT_CA. The trimethylamine N-oxide (TMAO) was lowest and S-equol highest in HICT_CA, whereas indoxyl sulfate (IS) peaked in HICT and was lowest in the C group. Principal component analysis revealed strong positive associations between HICT_CA and cardiometabolic biomarkers. Conclusions: High-intensity training combined with carnosine may reduce weight gain, improve lipid and glycemic profiles, and enhance myokines and microbiota-derived metabolites. Full article

Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide. According to the WHO, every year, there is an increase in the rate of death globally due to CVDs, stroke, and myocardial infarction. Several risk factors contribute to the development of CVDs, one of which is hypoxia, defined as a reduction in oxygen levels. This major stressor affects aerobic species and plays a crucial role in the development of cardiovascular disease. Research has uncovered the “hypoxia-inducible factors (HIFs) switch” and investigated the onset, progression, acute and chronic effects, and adaptations of hypoxia, particularly at high altitudes. The hypoxia signalling pathways are closely linked to natural rhythms such as the circadian rhythm and hibernation. In addition to genetic and evolutionary factors, epigenetics also plays an important role in postnatal cardiovascular responses to hypoxia. Oxidized LDL-C initiates atherosclerosis amidst oxidative stress, inflammation, endothelial dysfunction, and vascular remodelling in CVD pathogenesis. Anti-inflammatory and antioxidant biomarkers are needed to identify individuals at risk of cardiovascular events and enhance risk prediction. Among these, C-reactive protein (CRP) is a recognized marker of vascular inflammation in coronary arteries. Elevated pro-atherogenic oxidized LDL (oxLDL) expression serves as an antioxidant marker, predicting coronary heart disease in apparently healthy men. Natural antioxidants and anti-inflammatory molecules protect the heart by reducing oxidative stress, enhancing vasodilation, and improving endothelial function. For instance, the flavonoid quercetin exerts antioxidant and anti-inflammatory effects primarily by activating the Nrf2/HO-1 signaling pathway, thereby enhancing cellular antioxidant defense and reducing reactive oxygen species. Carotenoids, such as astaxanthin, exhibit potent antioxidant activity by scavenging free radicals and preserving mitochondrial integrity. The alkaloid berberine mediates cardiovascular benefits through activation of AMO-activated protein kinase (AMPK) and inhibition of nuclear factor kappa B [NF-kB] signalling, improving lipid metabolism and suppressing inflammatory cytokines. Emerging evidence highlights microRNAs (miRNAs) as potential regulators of oxidative stress via endothelial nitric oxide synthase (eNOS) and silent mating-type information regulation 2 homolog (SIRT1). While the exact mechanisms remain unclear, their benefits are likely to include antioxidant and anti-inflammatory effects, notably reducing the susceptibility of low-density lipoproteins to oxidation. Additionally, the interactions between organs under hypoxia signalling underscore the need for a comprehensive regulatory framework that can support the identification of therapeutic targets, advance clinical research, and enhance treatments, including FDA-approved drugs and those in clinical trials. Promising natural products, including polysaccharides, alkaloids, saponins, flavonoids, and peptides, as well as traditional Indian medicines, have demonstrated anti-hypoxic properties. Their mechanisms of action include increasing haemoglobin, glycogen, and ATP levels, reducing oxidative stress and lipid peroxidation, preserving mitochondrial function, and regulating genes related to apoptosis. These findings emphasise the importance of anti-hypoxia research for the development of effective therapies to combat this critical health problem. A recent approach to controlling CVDs involves the use of antioxidant and anti-inflammatory therapeutics through low-dose dietary supplementation. Despite their effectiveness at low doses, further research on ROS, antioxidants, and nutrition, supported by large multicentre trials, is needed to optimize this strategy. Full article

Obesity and overweight conditions, frequently accompanied by hypercholesterolemia, are major risk factors for cardiovascular disease. Lifestyle interventions remain the cornerstone of non-pharmacological treatment; however, their effectiveness in improving lipid profiles is limited. Intermittent hypoxic training (IHT) has recently emerged as a potential strategy to enhance metabolic outcomes. This study aimed to evaluate the effects of a 4-week intensive IHT program combined with a calorie-restricted diet on lipid profile and body composition in men with overweight or obesity and secondary hypercholesterolemia. Twenty physically inactive men (35.3 ± 5.4 years) were randomly assigned to either a hypoxic group (H, n = 10) or a normoxic control group (C, n = 10). Both groups followed the same training protocol and diet, differing only in environmental training conditions. Body composition, resting metabolic rate, and blood lipid parameters (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; non-high-density lipoprotein cholesterol, non-HDL-C; Triglycerides, TG) were assessed before and after the intervention. Compared with the C group, participants in the H group achieved significantly greater reductions in body mass (−5.4% vs. −2.6%, p < 0.05) and fat mass (−14.7% vs. −7%, p < 0.01). IHT also induced marked decreases in TC (−22.6%, p < 0.001), LDL-C (−25.8%, p < 0.001), non-HDL-C (−26.5%, p < 0.001), and TG (−31.4%, p < 0.01), along with a significant improvement in the atherogenic index of plasma (AIP, −24.4%, p < 0.05). In contrast, the C group showed only non-significant downward trends. No significant changes in HDL-C were observed in either group. These findings suggest that IHT combined with dietary restriction produces more favorable changes in lipid profile and body composition than normoxic training. IHT may therefore represent a promising adjunct to conventional lifestyle-based interventions in the management of obesity-related hypercholesterolemia. Full article

Background/Objectives: Overweight and obesity are associated with insulin resistance, atherogenic dyslipidemia, and low-grade inflammation. We evaluated analytical safety and within-person metabolic changes under the Adaptive Ketogenic–Mediterranean Protocol (AKMP) in real-world practice. Methods: Single arm, prospective pre–post cohort. We enrolled 112 adults; 105 completed 14 weeks of AKMP (12 in nutritional ketosis ≤ 20 g carbohydrate/day + 2 of gradual reintroduction). Fasting venous samples were analyzed in accredited laboratories (glycolipid profile, hepatic–renal function, inflammatory markers; insulin, thyroid hormones, cortisol). HOMA-IR, TyG, and remnant cholesterol (RC) were calculated; body composition was measured by segmental bioimpedance. Paired analyses were used, with hierarchical gatekeeping for the conditional co-primary outcome and prespecified Δ~Δ correlations. Results: HOMA-IR −52.8% (Δ −1.80; p < 0.001) and RC −35.1% (Δ −10.64 mg/dL; p < 0.001); fasting glucose −13.7 mg/dL, insulin −5.9 μU/L; TyG −0.23 and TG/HDL-c −1.21 (all p < 0.001). Lipids: TG −35.1% and LDL-c −11.2%; HDL-c remained stable. Anthropometry: weight −14.85 kg (−14.7%) and trunk fat −4.88 kg (−22.2%) (p < 0.001). Safety: no serious adverse events; GGT −47.0%, eGFR +11.0%, and CRP −24.6% (p < 0.001). Prespecified correlations supported the internal consistency of the glycolipid axis (e.g., ΔHOMA-IR~ΔTyG; ΔRC~ΔHOMA-IR). Conclusions: In adults with overweight or obesity, the AKMP was associated with improvements in the glucose–insulin axis, atherogenic profile (RC, TG/HDL-c, TG), and body composition, while maintaining a favorable safety profile. The protocol appears feasible in clinical practice and monitorable with routine laboratory tests, although randomized controlled trials are needed to confirm causality and long-term sustainability. Full article

Atherogenic dyslipidemia (AD) is a high-risk phenotype for cardiovascular disease, characterized by elevated triglycerides, increased small dense low-density lipoprotein cholesterol (sdLDL-C), and frequently coexisting hypertension. Although FTO gene variants have been implicated in lipid dysregulation, their role in AD among Latin American women remains poorly defined. We conducted a case–control study in 219 working perimenopausal women (97 AD cases and 122 controls). Sociodemographic, clinical, and biochemical variables were assessed. Three FTO SNPs (rs9939609, rs9940128, and rs8050136) were genotyped. Associations were evaluated using logistic regression models adjusted for age and BMI, with gene–environment interactions tested for smoking. Linkage disequilibrium (LD) and haplotype analyses were also performed. Women with AD exhibited significantly higher triglycerides, LDL-C, and sdLDL-C, along with increased hypertension prevalence, but no differences in BMI or glycemia. Multivariable models identified LDL-C (aOR ≈ 8), triglycerides, sdLDL-C, and systolic blood pressure as the strongest determinants of AD. The rs8050136 AA genotype was associated with a fourfold higher risk (aOR = 4.12; 95% CI: 1.49–11.95, p = 0.007). Smoking independently doubled AD risk (aOR = 2.33) and amplified the effect of rs8050136. Adjusted haplotype analysis revealed that the A-A-A (aOR = 5.33; 95% CI: 1.42–20.00) and A-G-A combinations (aOR = 2.54; 95% CI: 1.01–6.38) were significantly associated with AD. FTO polymorphisms, particularly rs8050136 and the A-A-A and A-G-A haplotypes, contribute independently and supra-additively to AD risk. The observed gene–environment interaction with smoking emphasizes the multifactorial nature of AD and supports genotype-based risk stratification and targeted preventive strategies in precision cardiovascular medicine. Full article

Background: The incidence of acute myocardial infarction (AMI) in young adults has been steadily rising, emphasizing the need for new biomarkers to improve risk stratification. Lipoprotein(a) (Lp(a)), a genetically determined lipoprotein with pro-atherogenic and pro-thrombotic properties, has gained increasing attention in this context. Methods: We evaluated serum Lp(a) levels in young patients with AMI and compared them with healthy controls. Associations between elevated Lp(a) levels (≥30 mg/dL) and coronary artery disease patterns were analyzed separately for STEMI and NSTEMI presentations. Results: Elevated Lp(a) levels were significantly more common in young patients with AMI compared with healthy controls. Importantly, Lp(a) ≥ 30 mg/dL was strongly associated with multivessel coronary artery disease in NSTEMI, conferring more than a fourfold increased risk. In STEMI, the effect was weaker and largely influenced by concomitant factors such as diabetes and elevated LDL cholesterol. Conclusions: These findings highlight key pathophysiological differences between infarct phenotypes and position Lp(a) as a particularly relevant biomarker in young NSTEMI patients. The systematic assessment of Lp(a) may enhance coronary risk stratification and support more tailored secondary prevention strategies. Full article

Background: Plaque protrusion after stent implantation is frequently observed in acute coronary syndrome (ACS) patients, yet studies on its long-term progression and clinical significance are limited. Methods: Seventy-eight ACS patients underwent optical coherence tomography (OCT)-guided PCI and follow-up OCT at 1 year. A total of 101 protruding lesions were classified into atherogenic neointima (AN) and non-AN groups based on OCT findings. Qualitative and quantitative assessments of protruding plaque, including irregularity and plaque intensity, were conducted. Results: AN developed in 17% of irregular protrusion (IP) lesions, whereas no smooth protrusion progressed to AN. Lesions in the AN group showed greater increases in protruding plaque volume (2.80 ± 0.46 mm² vs. 0.67 ± 0.16 mm², p < 0.001) and diameter stenosis (16.5% vs. 10.1%, p = 0.02). Follow-up LDL levels were higher in the AN group compared with the non-AN group (76.9 vs. 61.2 mg/dL, p = 0.02), despite similar baseline levels. Conclusions: Low-intensity IP after stent implantation in ACS patients carries a high risk of progression to AN, particularly under poor LDL control. Aggressive lipid-lowering therapy may mitigate this risk. Full article

Objective: This study aimed to compare the effects of empagliflozin and dapagliflozin on classical lipid parameters—including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)—as well as on atherogenic risk indices, including the atherogenic index of plasma (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), atherogenic coefficient (AC), and triglyceride-glucose index (TyG), in patients with heart failure and a history of coronary artery bypass grafting (CABG). To our knowledge, this is the first study to comprehensively evaluate these parameters in this high-risk population. Methods: This single-center, retrospective study included 484 patients with preserved ejection fraction heart failure and prior CABG who were treated with sodium–glucose cotransporter-2 (SGLT2) inhibitors. Patients were allocated to empagliflozin (n = 201) or dapagliflozin (n = 283) groups. All patients were receiving statin therapy. Lipid parameters and atherogenic indices were evaluated at baseline and after 12 weeks of treatment. Results: Both empagliflozin and dapagliflozin significantly reduced TC and LDL-C at 12 weeks (p < 0.001). No significant changes were observed in HDL-C or TG. Both agents produced significant improvements in CRI-I, CRI-II, AC, and TyG index (all p < 0.001), while AIP remained unchanged. Dapagliflozin achieved a greater reduction in TC (p = 0.044). Conclusions: This study represents the first direct comparison of empagliflozin and dapagliflozin on lipid profiles and atherogenic indices in patients with heart failure and prior CABG. Both agents significantly improved TC, LDL-C, and atherogenic indices. Dapagliflozin achieved a greater reduction in TC compared with empagliflozin, but overall both drugs demonstrated favorable and largely comparable effects. Beyond improvements in absolute values, both agents also contributed to favorable shifts in risk categories of lipid-derived indices. These findings suggest that clinical decision-making between empagliflozin and dapagliflozin may rely on factors other than lipid modulation. Larger multicenter prospective trials are warranted to confirm these results and clarify their long-term cardiovascular implications. Full article

Background: Dyslipidaemia promotes atherosclerotic plaque formation. Plaques that are vulnerable to rupture have a higher proportion of inflammatory (M1:CD86) macrophages in their cap. Many plaque macrophages are derived from blood monocytes which have been exposed to elevated blood lipid levels. Here, we explored whether the inflammatory state of monocyte-derived macrophages is associated with blood lipid levels and assessed whether oxidised low-density lipoprotein (oxLDL) directly induces some of the observed changes. Method: Blood was collected from 20 individuals. Lipid profiles were measured, and monocytes differentiated into macrophages. Macrophage inflammatory state was assessed by flow cytometry for phenotypic markers (e.g., CD86 and CD163) and cytokine production: TNF, IL-1β, and IL-6. Furthermore, monocytes were isolated from 6 normo-lipidaemic individuals and cultured with oxLDL, followed by stimulation with LPS/IFNγ and assessment of the cytokine response. Results: The inflammatory phenotype acquired by macrophages (ex vivo) was related to levels of in vivo circulating lipids. Correlations for CD86/CD163 were found with CVD risk markers; most strongly with triglycerides (TG) and TG/HDL-C, but also with cholesterol/HDL-C and ApoB/ApoA1 and inversely with LDL particle size. Functionally, macrophage production of inflammatory cytokines (TNF and IL-1β) correlated with oxLDL levels and inversely with ApoA1. Macrophages differentiated from monocytes cultured with oxLDL produced significantly higher IL-1β but lower IL-10 (in response to LPS/IFNγ), compared to control cells. Conclusions: Monocyte-derived macrophages adopt an inflammatory phenotype relative to the levels of circulating lipid factors that are characteristic of atherogenic dyslipidaemia (such as high TG, TG/HDL-C and low LDL particle size), but not LDL-C. Full article