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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 Funding Acknowledgements Type of funding sources: None. Immunomodulatory effect of different statin regimens on regulatory T-cells among patients with acute coronary syndrome: a systematic review and network meta-analysis of randomized clinical trials Introduction In patients with acute coronary syndrome (ACS), studies suggest that statin therapy, besides its role in reducing the progression of atherosclerosis through its pharmacological effect, plays a pivotal role in controlling the pathogenesis of ACS through the anti-inflammatory effects of suppressor regulatory T cells (Tregs). Purpose We conducted a network meta-analysis (NMA) to determine the effects of low-dose conventional statin therapy (CST) (20 mg/day or less) and high-dose intensive statin therapy (IST) (40 mg/day or more) on the frequency of Tregs and their associated cytokines (IFN-γ, IL-10, TGF-β), compared to placebo. Methods The PubMed, Cochrane Library, and EMBASE databases were searched for randomized clinical trials (RCTs) to identify relevant articles published until June 2021. We pooled data extracted from the included studies using the standardized mean difference (SMD). A random-effects model was used to conduct this NMA. Heterogeneity was evaluated using Cochran's Q- and the I2-test. GRADE(Grading of Recommendations, Assessment, Development and Evaluations) was used to assess the study's quality. Data analysis was conducted using R software. Results A total of 505 patients were enrolled in the 5 RCTs. The NMA indicated a significant increase in Treg frequency in the CST group compared with the control group (SMD 1.77; 95% CI: 0.77 – 2.76; P-value = 0.0005) and a larger increase in the Treg frequency associated with the IST group compared with the control group (SMD 2.12; 95% CI: 1.15 – 3.10; P-value < 0.0001). However, there was significant heterogeneity and inconsistency among the included studies (τ2 = 0.6096; τ = 0.7808; I2 = 91.2% [80.5%; 96.0%]). When compared to the placebo, both CST and IST increased levels of secreted IL-10 (SMD 2.69; 95% CI: 2.07 – 3.31; P-value < 0.0001 and (SMD 2.14; 95% CI: 1.76 – 2.52; P-value < 0.0001), respectively. In comparison to the control group, CST was associated with increased levels of TGF-β (SMD 3.83; 95% CI: 0.63 – 7.0; P-value = 0.0189). This association was not seen in the IST group. IFN-γ levels decreased significantly in both the IST and CST groups (SMD -1.52; 95% CI: -1.94 – -1.10; P-value < 0.0001) and (SMD -2.34; 95% CI: -2.73 – -1.95; P-value < 0.0001) respectively. Conclusions Our study suggests that both high and low dose statin groups showed increased Treg frequency compared to the placebo group. IST showed larger benefits. Statin therapy also increased IL-10 and TGF-β cytokine levels and decreased IFN-γ levels. Therefore, statins have the potential to be the main treatment to reduce the incidence of cardiovascular events and improve cardiac function in patients with ACS through immunomodulatory effect on Treg.

Introduction: Intracranial hemorrhage (ICH) is associated with high mortality rate of 30-52% despite current advances in management. New cardiovascular abnormalities (CA), such as EKG or cardiac biomarker abnormalities ensue in ICH and are postulated to be due to hypothalamic injury and catecholamine surge. These CA are thought to portend a poor prognosis. Methods: We evaluated clinical studies reporting CA in ICH and assessing their effect on mortality. Studies without a control group, pediatric, and non-English literature were excluded. We extracted data on demographics, comorbidities and mortality [in-hospital (IHM), 30 day (30M) and 90 day (90M)]. CA data included EKG changes (bradycardia, atrial fibrillation, bundle branch blocks, QTc prolongation, ST-segment depression, and ST-segment elevation), biomarker elevation (troponin-T (TnT), CK-MB and BNP), and wall motion abnormalities (WMA). Unadjusted and adjusted rates for CA and pooled risk ratio (RR) with 95% CI were calculated using Mantel-Haenszel random effects model for mortality. Results: We reviewed 453 studies, of which 26 met our inclusion criteria. Heterogeneity varied from moderate to severe depending on the outcome chosen. Of a total 5580 patients, 2796 (50.1%) had sub-arachnoid hemorrhage (SAH), 1633 ICH (29.3%) and 1151 (20.6%) both. The incidence of CA is presented in Table 1. Of these 26 studies, 19 evaluated the influence of new CA on mortality. IHM was noted in 175/566 (30.9%) and 491/2496 (19.7%) patients with and without CA, respectively. In addition, 30M and 90M were noted in 18/38 (47.4%) vs. 14/136 (10.3%) and 90/175 (51.4%) vs. 247/1139 (21.7%) patients with and without CA, respectively. CA was associated with worse IHM (RR 2.03, 95% CI 1.58-2.62, p<0.001), 30M (RR 3.18, 95% CI 1.86-5.42, p<0.001) and 90M (RR 2.11, 95% CI 1.44-3.08, p<0.001) in patients with ICH compared to those who did not have CA. Conclusion: CA are common in patients with ICH and are associated with worse IHM, 30M and 90M.

Background: The role of B-type natriuretic peptide (BNP) is less understood in the risk stratification of patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), especially in patients with normal left ventricular ejection fraction (LVEF). Methods: This retrospective study from 2008 to 2012 evaluated all adult patients with AECOPD having BNP levels and available echocardiographic data demonstrating LVEF ≥40%. The patients were divided into groups 1, 2, and 3 with BNP ≤ 100, 101 to 500, and ≥501 pg/mL, respectively. A subgroup analysis was performed for patients without renal dysfunction. Outcomes included need for and duration of noninvasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, reintubation at 48 hours, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed P < .05 was considered statistically significant. Results: Of the total 1145 patients, 550 (48.0%) met our inclusion criteria (age 65.1 ± 12.2 years; 271 [49.3%] males). Groups 1, 2, and 3 had 214, 216, and 120 patients each, respectively, with higher comorbidities and worse biventricular function in higher categories. Higher BNP values were associated with higher MV use, NIV failure, MV duration, and ICU and total LOS. On multivariate analysis, BNP was an independent predictor of higher NIV and MV use, NIV failure, NIV and MV duration, and total LOS in groups 2 and 3 compared to group 1. B-type natriuretic peptide continued to demonstrate positive correlation with NIV and MV duration and ICU and total LOS independent of renal function in a subgroup analysis. Conclusion: Elevated admission BNP in patients with AECOPD and normal LVEF is associated with worse in-hospital outcomes and can be used to risk-stratify these patients.

Pneumocystis jirovecii is responsible for P. jirovecii pneumonia (PJP) in immunocompromised individuals, with a recent rise of cases noted in non-HIV patients. A middle-aged man presented with new-onset cough, fever, hypoxia and tachypnoea. He was on a tapering course of dexamethasone for amiodarone-induced thyrotoxicosis. He developed worsening airspace disease necessitating mechanical ventilation. Bronchoalveolar lavage (BAL) fluid was positive for P. jirovecii and he was managed with trimethoprim/sulfamethoxazole and pentamidine, but succumbed to cardiorespiratory arrest. One-third of PJP cases occur in non-HIV patients, and have a higher morbidity and mortality. Most immunocompromised patients typically exhibit PJP during a corticosteroid taper. The accurate dose, duration or frequency of steroid use in not well established. Diagnosis of PJP in this population is more challenging due to lower BAL yield with alternate modalities such as serum/BAL β-d-glucan and PCR enhancing the yield. Further studies are needed to highlight PJP prophylaxis in patients with steroid use.