Tanashat, Mohammad

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

ABSTRACTBackground and ObjectiveSeladelpar is an oral, once‐daily medication that improves cholestasis through its selective peroxisome proliferator‐activated receptor (PPAR‐δ) agonism. It shows promising efficacy in treating primary biliary cholangitis (PBC) patients.MethodsA systematic review and meta‐analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Cochrane, Scopus, and WOS until July 19th, 2025. Dichotomous outcomes were reported using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI).ResultsThree RCTs with 499 patients were included. Seladelpar was significantly associated with an increased ALP normalization (RR: 21.12 with 95% CI [4.14, 107.58], p < 0.01), biochemical response (RR: 3.06 with 95% CI [2.00, 4.70], p < 0.01), and decreased pruritus NRS score change (MD: −1.47 with 95% CI [−2.73, −0.21], p = 0.02). Seladelpar was also significantly associated with a decreased incidence of pruritus (RR: 0.54 with 95% CI [0.31, 0.94], p = 0.03) but with an increased incidence of headache (RR: 3.37 with 95% CI [1.11, 10.23], p = 0.03). However, there was no significant difference between seladelpar and placebo regarding the incidence of any adverse events (RR: 0.96 with 95% CI [0.87, 1.06], p = 0.43).ConclusionSeladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse effects. This makes seladelpar a promising addition to the treatments available for PBC.Trial Registration: PROSPERO: CRD42024521208

Abstract Background While the cardioprotective effects of glucagon-like peptide -1 (GLP-10) agonists are well-documented in diabetic patients, their impact on cardiovascular outcomes in patients with obesity without diabetes mellitus remains debated. Purpose This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of GLP-1 on cardiovascular outcomes in patients with obesity without diabetes mellitus. Methods A systematic review and meta-analysis synthesizing RCTs were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 26th, 2023. Dichotomous data were pooled using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Results We included 19 RCTs with a total of 32,884 patients. There was no difference between GLP-1 agonists and placebo regarding cardiovascular mortality (RR: 0.85, 95% CI [0.71- 1.01], P= 0.07). However, GLP-1 agonists significantly decreased the incidence of all-cause mortality (RR 0.83, 95% CI 0.72 to 0.94, p &lt; 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63 to 0.96, p = 0.02), and myocardial infarction (RR 0.73, 95% CI 0.62 to 0.87, p &lt; 0.0001). Also, GLP-1 agonists significantly increased the incidence of any adverse events (RR 1.11, 95% CI 1.05 to 1.16, p &lt; 0.0001), with no difference regarding the incidence of serious adverse events. Conclusion GLP-1 agonists not only demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, but also effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.

Abstract Background Previous studies have suggested that pre-treatment of coronary artery calcification with rotational atherectomy (RA) prior to stent deployment can enhance procedural success, but this does not necessarily translate into improved clinical outcomes. Recently, the Orbital Atherectomy (OA) system has been introduced into clinical practice to enhance lesion preparation. Purpose Our study aims to evaluate the safety and efficacy of both RA and OA as pre-treatment strategies before stent deployment in patients with coronary artery calcification. Methods We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies. These were identified through systematic PubMed, Web of Science, Scopus, Embase, and Cochrane searches until January 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using Stata version 17. Results Our analysis included eleven studies encompassing 81,873 patients. No significant difference was observed between RA and OA in terms of major adverse cardiovascular events (MACE) (RR: 0.81 with 95% CI [0.64, 1.02], P= 0.07). However, OA was significantly associated with a decreased incidence of all-cause mortality (RR: 0.60 with 95% CI [0.52, 0.70], P&lt; 0.01), target vessel revascularization (TVR) (RR: 0.43 with 95% CI [0.22, 0.82], P= 0.01), coronary artery bypass grafting (CABG) (RR: 0.78 with 95% CI [0.62, 0.97], P= 0.03), and fluoroscopy time (MD: -3.93 with 95% CI [-7.39, -0.48], P= 0.03). There was no significant difference between RA and OA in cardiac death (RR: 2.65 with 95% CI [0.94, 7.51], P= 0.07), target lesion revascularization (TLR) (RR: 0.57 with 95% CI [0.23, 1.41], P= 0.22), myocardial infarction (RR: 0.79 with 95% CI [0.62, 1.01], P= 0.06), stent thrombosis (RR: 0.33 with 95% CI [0.09, 1.23], P= 0.10), stroke (RR: 0.76 with 95% CI [0.57, 1.01], P= 0.06), re-admission (RR: 0.76 with 95% CI [0.48, 1.19], P= 0.23), vessel closure (RR: 0.78 with 95% CI [0.18, 3.33], P= 0.74), procedural duration (MD: -5.43 with 95% CI [-21.71, 10.84], P= 0.51), length of hospital stay (MD: 0.21 with 95% CI [-0.47, 0.90], P= 0.54), and contrast amount (MD: -3.68 with 95% CI [-9.37, 2.01], P= 0.21). Conclusion Both RA and OA as pre-treatment strategies before stent deployment demonstrate similar outcomes for numerous cardiovascular events. However, OA is associated with lower rates of all-cause mortality, TVR, CABG, and fluoroscopy time.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed, EMBASE, WOS, SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5 : 2 diet significantly improved liver stiffness (MD, −0.32; 95% CI, −0.55 to −0.09; P < 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, −39.83; 95% CI, −64.78 to −14.87; P < 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction (P < 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.