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.
Major clinical outcomes in patients with symptomatic versus asymptomatic atrial fibrillation: a Bayesian and frequentist meta-analysis
Abstract Background Although a rhythm control strategy is associated with an overall better prognosis in atrial fibrillation (AF), current guidelines suggest that only highly selected asymptomatic patients may be considered candidates for AF catheter ablation. Therefore, this study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. Methods A comprehensive search of Medline, the Cochrane Library, and Scopus was conducted up until September 30, 2024. Study selection, data extraction, and quality assessment were performed independently by three reviewers. Random-effects meta-analyses were used to pool the evidence. Results A total of 36 studies, comprising 217,850 participants, were included. Frequentist analysis revealed no significant difference between symptomatic and asymptomatic AF patients in terms of all-cause mortality [hazard ratio (HR) = 0.97, 95% confidence interval (CI)= (0.80, 1.17)], cardiovascular mortality (HR= 1.04, 95% CI= [0.72, 1.49]), thromboembolism (HR= 1.06, 95% CI= [0.87, 1.28]), stroke (HR= 1.06, 95% CI= [0.84, 1.34]), hospitalization (HR= 1.34, 95% CI= [0.89, 2.02]), and myocardial infarction (HR= 0.98, 95% CI= [0.70, 1.36]). However, symptomatic patients exhibited a 33% increased risk of new-onset heart failure (HR= 1.33, 95% CI= [1.19, 1.49]) and a 30% reduced risk of progression to permanent AF (HR= 0.70, 95% CI= [0.54, 0.89]). Bayesian analysis produced similar results, although the association between symptom status and new-onset heart failure was not statistically significant [HR = 1.27, 95% credible interval (CrI)= (0.76, 1.93); Bayes factor (BF10)= 1.2]. Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR]= 1.64, 95% CI= [1.33, 2.03]) and ablation therapy (OR= 1.47, 95% CI= [1.06, 2.05]) compared to their asymptomatic counterparts. Conclusions The risk of major clinical outcomes does not significantly differ between AF patients with and without symptoms. However, asymptomatic patients have a higher risk of progressing to permanent AF.
Major clinical outcomes in symptomatic vs. asymptomatic atrial fibrillation: a meta-analysis
Abstract Background and Aims Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. Methods Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. Results Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80–1.17], cardiovascular mortality (HR 1.04, 95% CI .72–1.49), thromboembolism (HR 1.06, 95% CI .87–1.28), stroke (HR 1.06, 95% CI .84–1.34), hospitalization (HR 1.34, 95% CI .89–2.02), and myocardial infarction (HR .98, 95% CI .70–1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19–1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54–.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76–1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33–2.03) and ablation therapy (OR 1.47, 95% CI 1.06–2.05) compared to asymptomatic cases. Conclusions The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF.