Namin, Sara Montazeri

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.

Introduction: Resistant and uncontrolled hypertension pose persistent clinical and public health challenges. Renal denervation, a catheter-based procedure targeting renal sympathetic nerves, has emerged as a promising approach to lower blood pressure by reducing sympathetic overactivity. Hypothesis: A systematic review and meta-analysis of sham-controlled trials investigated whether renal denervation results in sustained blood pressure reduction across short-, medium-, and long-term follow-up. Methods: We searched PubMed, Embase, CENTRAL, and Web of Science through March 2025. The protocol was registered in PROSPERO (CRD420251015937). Randomized, sham-controlled trials of renal denervation in resistant/uncontrolled hypertension were included. Primary outcomes were ambulatory blood pressure (daytime, nighttime, and 24-hour); secondary outcomes included office and home blood pressure measurements. Follow-up durations were categorized into three groups: less than 6 months, 6–12 months, and greater than 12 months. Risk of bias was assessed using RoB-2. Results: Twenty trials (25 reports) with 2,167 RDN patients and 1,744 sham controls were included. Most trials had a low risk of bias. RDN significantly reduced 24-hour SBP (–3.29 mmHg, 95% CI: –5.91 to –0.67) and DBP (–1.42 mmHg, 95% CI: –2.29 to –0.55), despite high heterogeneity (I2 > 90%). Daytime DBP showed a significant reduction (–2.90 mmHg, 95% CI: –4.39 to –1.41), while other BP measures were less consistent. Home SBP was significantly reduced (–5.04 mmHg, 95% CI: –8.50 to –1.58). At 6–12 months, 24-hour SBP reduction persisted (–3.36 mmHg, 95% CI: –5.71 to –1.01), but DBP effects were nonsignificant. Long-term follow-up revealed nonsignificant changes in systolic blood pressure and diastolic blood pressure. Conclusions: Renal denervation modestly lowers BP in the short term (<6 months). Mid-term SBP reduction persists, but diastolic and long-term effects are inconsistent. These findings highlight the need for refined patient selection, optimized techniques, and longer follow-up trials.

ABSTRACTBackgroundComparisons of outcomes after transcatheter aortic valve replacement with balloon‐expandable (BEV) versus self‐expanding (SEV) valves are limited.HypothesisThis study aimed to compare clinical and hemodynamic outcomes of BEV and SEV at short‐term (30 days), midterm (1 year), and long‐term (> 1 year) endpoints.MethodsPubMed, Embase, Scopus, and Cochrane Library databases were searched until July 2024 for randomized controlled trials. Random‐effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences, and 95% confidence intervals (CI).ResultsA total of 10 studies comprising 4325 patients (2295 BEV, 2030 SEV) were included. In short‐term, cardiovascular (RR: 0.56, 95% CI: 0.36–0.87) and all‐cause mortality (RR: 0.54, 95% CI: 0.35–0.81) were lower in the BEV group. Risk of moderate to severe paravalvular leak (PVL) was lower among BEV patients in short‐term (RR: 0.28, 95% CI: 0.17–0.49) and long‐term (RR: 0.28, 95% CI: 0.1–0.79). A limited number of studies showed a greater risk of clinical valve thrombosis on BEV in midterm and long‐term. The need for permanent pacemaker implantation was lower in BEV at both short‐term (RR: 0.56, 95% CI: 0.37–0.87), and midterm (RR: 0.78, 95% CI: 0.64–0.94). The SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient at all endpoints.ConclusionsBEV is associated with reduced risk of clinical outcomes in short‐term; however, most differences diminish in longer evaluations, except for moderate to severe PVL, which remains elevated for SEV. SEVs had better hemodynamic results and lower risk of clinical valve thrombosis.

Background: The research on the outcomes of transcatheter aortic valve replacement with balloon-expandable valves (BEV) and self-expanding valves (SEV) are limited. Hypothesis: This study aims to compare the clinical and hemodynamic outcomes of BEV and SEV at short-term (30 days), mid-term (1 year), and long-term (>1 year) endpoints. Methods: PubMed, Embase, Scopus, and Cochrane Library databases were searched up to April 25, 2024, for randomized controlled trials (RCTs). Random-effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences (MD) and 95% confidence interval (CI) for binary and continuous outcomes, respectively. Results: A total of 11 RCTs comprising 4,325 patients (2,295 BEV, 2,030 SEV) were included. At short-term, the risk of cardiovascular (RR: 0.56, 95% CI: 0.36-0.87) and all-cause mortality (RR: 0.54, 95% CI: 0.35-0.81) were lower in the BEV group. However, no differences were noted between the two treatment modalities in longer follow-ups despite the lower risk of moderate to severe paravalvular leak (PVL) among BEV patients. The risk of stroke was comparable between two groups across all three follow-up endpoints, albeit a limited number of studies suggesting the BEV group showed a greater risk of clinical valve thrombosis in mid-term and long-term assessments. The need for permanent pacemaker implantation was lower in BEV arm in short-term (RR: 0.56, 95% CI: 0.37-0.87) and mid-term (RR: 0.78, 95% CI: 0.64-0.94). Yet, this difference was not observed in long-term follow-ups. Conversely, the SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient from short-term (MD: 0.17, 95% CI: 0.07-0.26 and MD: 3.71, 95% CI: 2.64-4.78, respectively) to long-term (MD: 0.25, 95% CI: 0.17-0.32 and MD: 3.73, 95% CI: 3.19-4.27, respectively) periods. Conclusions: BEV is associated with reduced risk of clinical outcomes at short-term; however, most differences diminish in longer evaluations, except for moderate to severe PVL. Conversely, SEV is linked to better hemodynamic outcomes and a lower risk of clinical valve thrombosis across all follow-up durations.