Patoulias, Dimitrios

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.

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.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

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.