Search Results (358)

Background and Objectives: Patients with atherosclerotic cardiovascular disease (ASCVD) remain at high risk of recurrent events. REALITY aims to analyse the actual levels of low-density lipoprotein cholesterol (LDL-C), the modalities of lipid-lowering therapies (LLT) used, and ASCVD patient outcomes in a real-world setting in Spain. Methods: REALITY is a retrospective observational study conducted using a healthcare database of 1.8 million patients representative of the Spanish population. The study included 26,976 patients with new or recurrent ASCVD events recruited from 2017 to 2019 and followed up for two years. Results: Management of ASCVD involved the utilisation of high-intensity (53%) or very high-intensity (36%) LLT. After two years, a decrease in total cholesterol (from 228.7 to 176.7 mg/dL), LDL-C (from 126.4 to 99.0 mg/dL), and triglycerides (from 216.7 to 163.7 mg/dL), accompanied by a moderate increase in HDL-C levels was observed. However, LDL-C goals of ESC/EAS guidelines were only reached by a minority of patients. Less than 15% of ASCVD patients achieved their LDL-C goals of <70, as stated in contemporary guidelines (3% if the present <55 mg/dL threshold in the ESC/EAS guidelines is considered). During the follow-up period, 9% of ASCVD patients died and 25% experienced a new ASCVD event. Conclusions: In the REALITY study, most patients did not achieve their target LDL-C goals despite receiving high- or very high-intensity LLT. Increasing the utilisation of extreme LLT is crucial to reducing recurrent ASCVD events and mitigating these patients’ high morbidity and mortality risk. Full article

Background: Coronary heart disease (CHD) remains a leading cause of death and has been associated with alterations in plasma lipoprotein particles and inflammation markers. This study aimed to evaluate and compare standard and advanced lipid parameters and inflammatory biomarkers in CHD cases and matched control subjects. We hypothesized that incorporating advanced lipid and inflammatory biomarkers into risk models would improve CHD risk prediction beyond the standard lipid measures. Methods: CHD cases (n = 227, mean age 61 years, 47% female) and matched controls (n = 526) underwent fasting blood collection while off lipid-lowering medications. Automated chemistry analyses were performed to measure total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-C (LDL-C), small dense LDL-C (sdLDL-C), apolipoproteins (apos) A-I and B, lipoprotein(a) (Lp(a)), high-sensitivity C-reactive protein (hsCRP), serum amyloid-A (SAA), myeloperoxidase (MPO), and apoA-I in HDL particles (via 2-dimensional electrophoresis and immunoblotting). Univariate, multivariate, and machine learning analyses compared the CHD cases with the controls. Results: The most significant percent differences between male and female cases versus controls were for hsCRP (+78%, +200%), MPO (+109%, +106%), SAA (+84%, +33%), sdLDL-C (+48%; +43%), Lp(a) (+43%,+70%), apoA-I in very large α-1 HDL (−34%, −26%), HDL-C (−24%, −27%), and apoA-I in very small preβ-1 HDL (+17%; +16%). Total C, non-HDL-C, and direct and calculated LDL-C levels were only modestly higher in the cases. Multivariate models incorporating advanced parameters were statistically superior to a standard model (C statistic: men: 0.913 vs. 0.856; women: 0.903 versus 0.838). Machine learning identified apoA-I in preβ-1-HDL, α-2-HDL, α-1-HDL, α-3-HDL, MPO, and sdLDL-C as the top predictors of CHD. Conclusions: This study introduces a novel approach to CHD risk assessment by integrating advanced HDL particle analysis and machine learning. By assessing HDL subpopulations (α-1, α-2, preβ-1 HDL), inflammatory biomarkers (MPO, SAA), and small dense LDL, we provide a more refined stratification model. Notably, preβ-1 HDL, an independent risk factor reflecting impaired cholesterol efflux from the artery wall, is highlighted as a critical marker of CHD risk. Our approach allows for earlier identification of high-risk individuals, particularly those with subtle lipid or inflammatory abnormalities, supporting more personalized interventions. These findings demonstrate the potential of advanced lipid profiling and machine learning to enhance CHD risk prediction. Full article

Background: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the accumulation of fat in the liver without excessive alcohol consumption or other known liver diseases. MASLD is the most common liver disease in adolescents with obesity. The aims of this study were as follows: (i) to determine which index (waist circumference BMI, WHtR, VAI, METS-IR, METS-VF, HSI, FLI, or MetS_zscore) best explains the prevalence of MASLD in adolescents with obesity; (ii) to determine whether there was a specific index that was most strongly associated with MASLD; (iii) to assess which liver function indexes were most strongly correlated with MASLD. Methods: A total of 758 adolescents with severe obesity (BMI z-score > 2) admitted at the Division of Auxology, Istituto Auxologico Italiano, IRCCS, Piancavallo-Verbania for a 3-week multidisciplinary body weight reduction program were selected. Anthropometric parameters (stature, body mass, BMI, and waist and hip circumference) were collected, and body composition (lean and fat mass) was determined using the tetrapolar bioimpedance analysis (BIA) technique. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and C-reactive protein (CRP) were measured using standard techniques. MASLD was diagnosed based on abdominal ultrasound results. Results: WHtR (65.76%) was the most sensitive compared with other indexes. The HSI (AUC: 0.67 (0.63–0.71, 95% CI), p-value < 0.05) showed the best performance in predicting MASLD, with the threshold for having MASLD considered at 48.22. The indexes that showed the worst performance in predicting MASLD were the MetS z-score (AUC: 0.56 (0.52–0.60)) and the VAI (AUC: 0.57 (0.52–0.61)). ALT (OR: 2.92 (2.29–3.77); 95% CI) and AST (OR: 2.52 (2.03–3.20)) were the parameters with a stronger correlation with MASLD. Conclusions: The most sensitive index for diagnosing MASLD was the WHtR, based exclusively on anthropometric parameters. HSI was the index that correlated the most with MASLD, while the parameters of liver function (ALT and AST) were the most strongly correlated with the disease and its severity. Full article

Diabetes mellitus is a chronic, degenerative, and multifactorial disease characterized by hyperglycemia, and at least 537 million people suffered from diabetes in 2021. Agave durangensis Gentry, a species of agave native to the state of Durango, reports phenolic compounds, flavonols, flavonoids, and saponins and could be an alternative for the treatment of diabetes. The aim of this work was to identify the compounds in the leaves of Agave durangensis Gentry and their potential activity in diabetes. The leaf extract of Agave durangensis Gentry (EAD) was characterized by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), and different families of bioactive compounds were quantified by analytical methods. Probable pharmacological targets were identified in silico, and the inhibition of dipeptidyl peptidase-4 (DPP4) was validated in vitro. A model of hyperglycemia was established with streptozotocin in male Wistar rats, and we administered EAD intragastrically at a dose of 300 mg/kg, as well as combinations of the extract with metformin and sitagliptin over 30 days. Biochemical and histological parameters were analyzed. We identified thirty-six major compounds, where triterpenes represented 30% of the extract. Molecular docking showed that the extract could interact with α-glucosidases and DPP4 since a large number of compounds in the extract have a Δ G lower than that reported for the controls, and DPP4 inhibition was confirmed by in vitro assays. In vivo assays demonstrated that the administration of the extract was able to significantly decrease glucose levels by 56.75% and glycosylated hemoglobin by 52.28%, which is higher than that reported for sitagliptin with a decrease of 35.22%. In addition, the extract decreased triglycerides by 59.28% and very-low-density lipoprotein (VLDL) cholesterol by 60.27%, and when administered in combination with metformin, it decreased them more than when metformin was administered alone. For all the above reasons, Agave durangensis Gentry extract could be used for the development of phytomedicine for the treatment of diabetes. Full article

Background/Objectives: Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. Methods: The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. Results: The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin (−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. Conclusions: This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients. Full article

The liver plays a crucial role in maintaining lipid homeostasis by converting toxic free fatty acids into VLDL, which the body uses for energy. Even minor changes in VLDL formation and secretion can result in serious health conditions such as atherosclerosis and non-alcoholic fatty liver disease. Despite the importance of VLDL, the proteins and signaling pathways involved in its regulation remain largely unknown. This study aims to develop a novel methodology to study intracellular VLDL transport events and explore the role of liver fatty acid-binding protein (LFABP) in VLDL transport and secretion. Current methods to study VLDL are often tedious, time-consuming, and expensive, underscoring the need for an alternative approach. We designed a new immunofluorescence-based assay to track the formation and secretion of VLDL in cells over time using fluorescently tagged TopFluor oleic acid. Confocal microscopy confirmed that TopFluor oleic acid enters hepatocytes and colocalizes with the ER, Golgi, and plasma membrane. Additionally, the collection of cell culture media revealed that TopFluor was incorporated into VLDL particles, as confirmed by fluorescence readings and ApoB100 immunoblots. This novel assay provides a valuable tool for further research into the mechanisms of VLDL regulation and the development of potential therapeutic targets for related diseases. Utilizing this assay, we identified LFABP as a key regulatory protein in post-Golgi VLDL trafficking. Our data suggest that LFABP plays a crucial role in this process, and its functional impairment leads to reduced VLDL secretion. Full article

There is growing evidence linking growth differentiation factor 15 (GDF15) to both metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular (CV) risk. Nevertheless, the potential relationship between circulating levels of GDF15 and key features of MASLD being predisposed to atherosclerotic CV disease is not fully unveiled. The aim of this study was to deepen into the role of circulating GDF15 levels on metabolic-associated liver injury and atherosclerotic CV disease. We determined the serum GDF15 levels in 156 participants of a metabolic patient-based cohort, and cross-sectionally explored its associations with liver injury and an advanced atherosclerotic lipoprotein profile assessed by nuclear magnetic resonance (¹H-NMR). Additionally, we prospectively evaluated the association between GDF15 levels at baseline and incident atherosclerotic CV disease after a 10-year follow-up. GDF15 was related to liver injury and inflammatory hallmarks, and it increased the likelihood for liver steatosis independently of confounding factors. Likewise, GDF15 was positively associated with an atherogenic profile, particularly with the number of very-low-density lipoproteins (VLDL) particles and its cholesterol and triglyceride content, and with an indicator of subclinical atherosclerosis (i.e., carotid intima–media thickness (cIMT)). The baseline serum GDF15 levels were higher in the patients with atherosclerotic CV disease (10.6%) after a 10-year follow-up than in the individuals without CV disease. Altogether, this study provides new insights into the role of GDF15 in both MASLD and CV disease. Full article

Background/Objectives. An elevated body mass index (BMI) has been added to the new American Heart Association atherosclerotic cardiovascular disease (ASCVD) risk model. Our goal in this study was to examine the relationships between BMI and traditional and non-traditional ASCVD risk factors. Methods. We measured levels of blood glucose, insulin, lipids, lipoproteins, sterols, fatty acids, markers of inflammation and oxidative stress, and hormones in 226,000 middle-aged and elderly subjects (55% women) and associated those parameters to BMI in 5 groups (BMI 20–25, 25.1–30, 30.1–35, 35.1–40, and >40 kg/m²). Results. BMI and age were inversely correlated in both sexes. All of the traditional and non-traditional ASCVD risk markers, except low-density lipoprotein cholesterol (LDL-C), changed significantly in unfavorable ways in both sexes with increasing BMI. The largest changes were observed in the high sensitivity C-reactive protein, which increased 6- and 8-fold, and insulin, which increased 4- and 3-fold between the lowest and highest BMI groups in men and women, respectively. Although the LDL-C levels changed little, small dense LDL-C and triglyceride levels increased significantly with increasing BMI. Markers of cholesterol synthesis were positively associated with BMI, while markers of cholesterol absorption and omega-3 fatty acids were inversely associated with BMI. Concentrations of high-density lipoprotein cholesterol (HDL-C) and the athero-protective, large-size HDL particles were also inversely associated with BMI. Our analysis indicated that the associations between an elevated BMI and unfavorable changes in major ASCVD risk factors were independent of age in both sexes. Moreover, we observed that ASCVD risk factors started changing unfavorably with increasing BMI even in the normal weight range (BMI 20–25 kg/m²). Conclusions. An elevated BMI is associated with unfavorable changes in traditional and non-traditional ASCVD risk factors independent of age. Therefore, maintaining a normal BMI, preferably by an active lifestyle, and, if necessary, weight-managing medication, is very important to avoid developing conditions leading to ASCVD. Full article

Disrupted clearance of amyloid beta (Aβ) from the brain enhances its aggregation and formation of amyloid plaques in Alzheimer’s disease. The most abundant protein constituent of circulating high-density lipoprotein (HDL) particles, apoA-I, readily crosses the blood–brain barrier from periphery circulation, exhibits low-micromolar binding affinity for soluble, neurotoxic forms of Aβ, and modulates Aβ aggregation and toxicity in vitro. Its highly conserved N-terminal sequence, ⁴²LNLKLLD⁴⁸ (‘LN’), has been proposed as a binding region for Aβ. However, high-resolution structural characterisation of the mechanism of HDL–Aβ interaction is very difficult to attain. Molecular dynamics simulations were conducted to investigate for the first time the interaction of Aβ and the ‘LN’ segment of apoA-I. Favourable binding of Aβ by HDLs was found to be driven by hydrophobic and hydrogen-bonding interactions predominantly between the ‘LN’ segment of apoA-I and Aβ. Preferential binding of Aβ may proceed in small, protein-rich HDLs whereby solvent-exposed hydrophobic ‘LN’ segments of apoA-I interact specifically with Aβ, stabilising it on the HDL surface in a possibly non-amyloidogenic conformation, facilitating effective Aβ clearance. These findings rationalise the potentially therapeutic role of HDLs in reducing Aβ aggregation and toxicity, and of peptide mimics of the apoA-I interacting region in blocking Aβ aggregation. Full article

Background/Objectives: Metabolic syndrome is a significant public health issue, particularly in urbanizing regions like the Peruvian Amazon, where lifestyle changes have increased the prevalence of metabolic disorders. This study aimed to develop and validate a simple, cost-effective diagnostic model for early detection of metabolic syndrome in the urban population of San Juan Bautista, Iquitos. Methods: A cross-sectional study was conducted with 251 adults aged over 18 years. Data collection included anthropometric measurements, body composition analysis, and biochemical assessments. Logistic regression analyses identified key predictors of metabolic syndrome, and clinical decision trees were developed to enhance diagnostic accuracy. Results: The prevalence of metabolic syndrome was 47.9%. Systolic blood pressure, triglycerides, and very-low-density lipoprotein cholesterol were the strongest predictors. The most effective diagnostic model, combining very-low-density lipoprotein cholesterol and systolic blood pressure, achieved a sensitivity of 91.6% and a specificity of 78.5%, demonstrating high diagnostic accuracy. Conclusions: The proposed model offers a practical, low-cost tool for early detection of metabolic syndrome in resource-limited urban settings. However, its findings are limited by the small sample size and the lack of external validation, requiring further studies to confirm its generalizability and applicability to other populations. Its implementation in primary healthcare could facilitate timely interventions, reducing the risk of chronic diseases in vulnerable populations. Full article

Background: Cytochrome P450 2B6 (CYP2B6) is a sexually dimorphic, anti-obesity CYP enzyme responsible for the metabolism of xeno- and endobiotics, including the metabolism of polyunsaturated fatty acids (PUFAs) into 9-hydroxyoctadecadienoic acid (9-HODE) and 9-hydroxyoctadecatrienoic acid (9-HOTrE). However, humanized CYP2B6 transgenic (hCYP2B6-Tg) mice are sensitive to diet-induced hepatic steatosis despite their resistance to obesity. The purpose of this study was to determine if 9-HODE, 9-HOTrE, or other factors contribute to the sexually dimorphic steatosis observed in hCYP2B6-Tg mice. Results: Cyp2b9/10/13-null (Cyp2b-null) mice were injected with either 9-HODE or 9-HOTrE for 2 days and were then subjected to a fasting period of 20 h to induce steatosis. Serum lipids were moderately increased, especially in females, after 9-HODE (triglycerides (TGs), very low-density lipoproteins (VLDLs)) and 9-HOTrE (high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), cholesterol) treatment. No change in hepatic lipids and few changes in hepatic gene expression were observed in mice treated with either oxylipin, suggesting that these oxylipins had minimal to moderate effects. Therefore, to further investigate CYP2B6’s role in steatosis, hCYP2B6-Tg and Cyp2b-null mice were subjected to a 20 h fast and compared. Both male and female hCYP2B6-Tg mice exhibited increased steatosis compared to Cyp2b-null mice. Serum cholesterol, triglycerides, HDLs, and VLDLs were increased in hCYP2B6-Tg males. Serum triglycerides and VLDLs were decreased in hCYP2B6-Tg females, suggesting the greater hepatic retention of lipids in females. Hepatic oxylipin profiles revealed eight perturbed oxylipins in female hCYP2B6-Tg mice and only one in males when compared to Cyp2b-null mice. RNA-seq also demonstrated greater effects in females in terms of the number of genes and gene ontology (GO) terms perturbed. There were only a few overlapping GO terms between sexes, and lipid metabolic processes were enriched in hCYP2B6-Tg male mice but were repressed in hCYP2B6-Tg females compared to Cyp2b-nulls. Conclusions: hCYP2B6-Tg mice are sensitive to fasting-mediated steatosis in males and females, although the responses are different. In addition, the oxylipins 9-HODE and 9-HOTrE are unlikely to be the primary cause of CYP2B6’s pro-steatotic effects. Full article

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) and obesity contribute to vascular dysfunction through oxidative stress, heightening cardiovascular risk. Oral supplementation with L-citrulline (L-cit), a precursor of L-arginine (L-arg) and nitric oxide, and high-intensity interval training (HIIT) may improve vascular function and cardiometabolic health. Objectives: This study aimed to evaluate the combined effects of L-cit supplementation and HIIT on arterial stiffness, body composition, glucose metabolism, lipid profile, and blood pressure (BP) in adolescents with MASLD and obesity. Methods: In this double-blind, placebo-controlled, randomized clinical trial (ClinicalTrials.gov (NCT05778266), 44 adolescents (15–19 years) with MASLD and obesity were assigned to HIIT + L-cit (n = 14), HIIT + placebo (n = 14), or L-cit (n = 15) for 12 weeks. HIIT sessions (85% and 60% peak heart rate during intense and recovery periods) occurred thrice weekly. Training volume progressively increased, and participants performed 20 min of HITT per session in the last 8 weeks. Results: Outcomes included pulse wave velocity (PWV), augmentation index (Aix75), VO2peak, body composition, BP, glucose and lipid profiles, and hepatic steatosis. Compared to L-cit, HIIT + L-cit improved non-high-density lipoprotein cholesterol (p = 0.04), very-low-density lipoprotein cholesterol (p = 0.01), triglycerides (p = 0.02), and VO2peak (p = 0.001). No significant between-group changes were found in PWV, AIx75, hepatic steatosis, and body composition. HIIT + placebo improved VO2peak (p = 0.002), and L-cit decreased the degree of steatosis (p = 0.038). Conclusions: HIIT + L-cit supplementation enhanced lipid profile and cardiorespiratory fitness, while HIIT + placebo improved cardiorespiratory capacity, and L-cit alone decreased hepatic steatosis. Thus, L-cit could be an adjuvant strategy to manage obesity-related MASLD in adolescents. Full article

Lipoprotein(a) [Lp(a)] is a well-established causal risk factor for cardiovascular diseases (CVDs), as reported by multiple Mendelian randomization studies and large epidemiological studies. When elevated Lp(a) is combined with other risk factors, most notably elevated low-density lipoprotein cholesterol (LDL-C), a synergistic atherogenic effect has been reported. However, the current literature is conflicting regarding how Lp(a) interacts in the context of controlled LDL-C levels (e.g., <70 mg/dL) and whether reducing LDL-C can modify the atherogenic effect of Lp(a). In some studies, elevated Lp(a) was still significantly associated with a higher risk of cardiovascular events, despite controlled levels of LDL-C. In contrast, multiple studies have reported attenuation of the cardiovascular risk mediated by elevated Lp(a) with lower LDL-C levels. Moreover, the relationship between Lp(a) and triglycerides, high-density lipoprotein, and very low-density lipoprotein remains unclear. In this literature review, we summarize and discuss the current evidence regarding the interactions between Lp(a) and other lipid molecules, how they contribute to the pathogenesis of CVD, and future perspectives, particularly in the current era where promising targeted Lp(a)-lowering therapies are under development. Full article

Background/Objectives: This study assessed the proportion of secondary cardiovascular prevention patients who achieved low-density lipoprotein (LDL) cholesterol targets as per the 2019 ESC/EAS Dyslipidemia Guidelines. We also evaluated whether lipid-lowering therapies (LLTs) were adjusted in patients not meeting targets and analyzed the likelihood of these modifications achieving recommended levels. Methods: A multicenter, cross-sectional observational study retrospectively reviewed medical records of 1909 outpatients in 9 Italian cardiac rehabilitation/secondary prevention clinics from January 2023 to June 2024. Inclusion criteria included prior atherosclerotic cardiovascular disease (ASCVD) and recent LDL-cholesterol levels. Data included demographics, ASCVD presentation, lipid profiles, and LLTs. Patients at very high risk had LDL targets of ≤55 mg/dL, or ≤40 mg/dL for recurrent events within 2 years. Clinicians’ approaches to LLT modification in patients not at target were recorded, with LLT efficacy estimated based on percentage distance from LDL-cholesterol targets. Results: Of the 1909 patients, 41.3% met the LDL-cholesterol target. Predictors of achieving targets included male gender, cardiac rehabilitation, recent acute coronary syndrome, diabetes, and triple therapy (statin + ezetimibe + PCSK9 inhibitors). Conversely, a target of ≤40 mg/dL, lack of therapy, and monotherapy were negative predictors. Among 1074 patients not at target, LLT modifications were proposed for 48.6%. Predictors of LLT modification included recent ASCVD events, cardiac rehabilitation, and greater percentage distance from the LDL target, while advanced age and an LDL target of ≤40 mg/dL were negative predictors. However, only 42.3% of modified therapies were predicted to be effective in reaching LDL targets. Conclusions: Despite 2019 ESC/EAS guidelines, a significant proportion of high-risk patients did not achieve LDL targets, and proposed LLT modifications were often insufficient. More intensive LLT regimens are needed to improve outcomes in this population. Full article

Background/Objectives: This systematic review and meta-analysis aimed to investigate the effect of prebiotics, alone or as part of synbiotics, on cardiometabolic parameters in polycystic ovary syndrome (PCOS) women. Methods: Databases, including PubMed, Scopus, ISI Web of Science, Embase, and the Cochrane Central Register of Controlled Trials, were searched for relevant randomized-controlled trials (RCTs) until 12 December 2024. Changes in mean ± standard deviations were extracted and combined using a random-effects model. Bias was assessed using Cochrane risk of bias and evidence quality with GRADE. Results: Twenty RCTs with 1271 participants were included. Results showed high-quality evidence supporting prebiotics’ effects, alone or as part of synbiotics, in reducing body-mass index [n = 853; weighted-mean difference (WMD): −0.510, 95%CI: −0.669, −0.351 kg/m²] and diastolic blood pressure (WMD: −2.218, 95%CI: −4.425, −0.010 mmHg), moderate-quality evidence for weight, waist-to-hip ratio, and triglycerides improvements, and low or very-low-quality evidence for waist circumference (WC), fat mass, fasting plasma glucose, fasting insulin, low-density lipoprotein (LDL), total cholesterol (TC), high sensitive-C reactive protein, total testosterone, follicle-stimulating hormone and free androgen index improvements. Subgroup analyses revealed possible reduction in LDL with prebiotics, as well as possible decreases in WC, TC, and total testosterone with synbiotics. Dietary approaches to stop hypertension diet improved insulin sensitivity. Conclusions: This study suggests that prebiotics may beneficially affect several cardiometabolic parameters in PCOS women. Approximately one-third of the results were based on moderate-to-high-quality evidence. This study highlights the need for future well-designed, larger RCTs with longer treatment duration to strengthen the evidence base and guide clinical decision-making. Full article