Raja, Adarsh

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.

Background: Hypertriglyceridemia, a common lipid disorder linked to increased risks of cardiovascular diseases and metabolic syndrome, remains a global health challenge. Traditional treatments, though widely used, often have limited efficacy and adverse effects. Olezarsen, a novel antisense oligonucleotide, targets apolipoprotein C-III and shows promise in significantly reducing triglyceride levels. Aim: To conduct a meta-analysis comparing Olezarsen with placebo in patients with hypertriglyceridemia. Methods: We performed an extensive literature search of PubMed, EMBASE, and Cochrane Library databases up to May 2024 to identify studies comparing Olezarsen and placebo in patients with hypertriglyceridemia, irrespective of comorbid cardiovascular disease. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs) for each. Results: Three randomized controlled trials (RCTs) with a total of 334 participants were included. Olezarsen significantly reduced triglyceride levels at 6 months (SMD: -1.69; 95% CI -2.22 to -1.17; P < 0.00001; Figure ) and 12 months (SMD: -1.64; 95% CI -2.22 to -1.07; P < 0.00001; Figure ). VLDL levels also decreased at 6 months (SMD: -1.95; 95% CI -2.38 to -1.51; P < 0.00001) and 12 months (SMD: -0.83; 95% CI -1.13 to -0.53; P < 0.00001). Lipid profile improvements included reductions in total cholesterol, non-HDL cholesterol, and apoB levels, with increases in HDL cholesterol and apoA-1. Adverse events were comparable between Olezarsen and placebo, although serious adverse events were significantly higher in the Olezarsen group (RR: 2.55; 95% CI 1.17 to 5.58; p = 0.02). Conclusion: Olezarsen demonstrates significant efficacy in reducing triglyceride and VLDL levels while improving overall lipid profiles in hypertriglyceridemia patients. Despite higher rates of serious adverse events, its overall safety profile remains acceptable.

Background: Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. Methods: We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. Results: In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: −6.01, 95% CI [−11.14, −0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: −537.17, 95% CI [−758.89, −315.45]), troponin T (MD: −1.71, 95% CI [−2.11, −1.32]), creatine phosphokinase-MB (MD: −2.96, 95% CI [−5.84, −0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. Conclusion: No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-β agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom’s use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) −4.61, 95% CI −6.77 to −2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74–3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20–4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.