Citations

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.

The evaluation of diffuse lung disease invariably involves chest computerized tomography (CT). The detailed information obtained is often equivalent to that from lung biopsies. It, however, involves exposure to ionising radiation which limits its repeated application in monitoring and follow up. Ultrasound techniques offer potentially safer/cheaper alternatives and lung ultrasound surface wave elastography (LUSWE) is a novel, noninvasive, and clinically feasible technique to quantify lung stiffness, an important biomechanical property that changes in diffuse fibrotic and infiltrative lung diseases. We have developed a sensitive, accurate and reproducible technique to measure changes in lung surface stiffness by using surface wave transmission speed and demonstrated its value in detecting and staging the degree of fibrosis in diffuse interstitial lung diseases, specifically idiopathic pulmonary fibrosis and progressive systemic sclerosis associated lung disease, as well as changes in heart failure. The technique consists of ultrasound detection of the propagation speed of a wave generated by the vibrations from an indenting shaker in multiple intercostal spaces to provide a representative assessment of both lungs. It offers the prospect of simple, radiation-free, repetitive assessment of changes in acute and chronic diffuse lung diseases with the potential for easy and rapid bedside use, all important considerations in clinical practice.

Objective: The objective of this study is to predict in vivo lung mass density for patients with interstitial lung disease using different gradient boosting decision tree (GBDT) algorithms based on measurements from lung ultrasound surface wave elastography (LUSWE) and pulmonary function testing (PFT). Methods: Age and weight of study subjects (57 patients with interstitial lung disease and 20 healthy subjects), surface wave speeds at three vibration frequencies (100, 150, and 200 Hz) from LUSWE, and predicted forced expiratory volume (FEV1% pre) and ratio of forced expiratory volume to forced vital capacity (FEV1%/FVC%) from PFT were used as inputs while lung mass densities based on the Hounsfield Unit from high resolution computed tomography (HRCT) were used as labels to train the regressor in three GBDT algorithms, XGBoost, CatBoost, and LightGBM. 80% (20%) of the dataset was used for training (testing). Results: The results showed that predictions using XGBoost regressor obtained an accuracy of 0.98 in the test dataset. Conclusion: The obtained results suggest that XGBoost regressor based on the measurements from LUSWE and PFT may be able to noninvasively assess lung mass density in vivo for patients with pulmonary disease.

Many lung diseases including interstitial lung disease (ILD) are associated with changes in the lung’s biomechanical properties. ILD comprises a number of serious diseases in which fibrosis stiffens and damages lung tissue. Most ILDs are typically distributed in the lung’s peripheral and subpleural regions. Pulmonary function test (PFT) and high-resolution computed tomography (HRCT) are used to assess ILD. Ultrasonography is not widely used for lung assessment because ultrasound cannot image deep lung tissue. We have developed lung ultrasound surface wave elastography (LUSWE) for measuring superficial lung wave speed. In LUSWE, a 0.1-s harmonic vibration is generated on the chest wall of a subject using a handheld vibrator. An ultrasound probe is aligned with the vibration excitation in the same intercostal space to measure the generated surface wave propagation on the lung. A human subject is examined in a sitting position. The lung is tested at the total lung volume and through six intercostal spaces. Significant differences of surface wave speed between patients and controls were found in 6 lung regions and for 3 excitation frequencies. A positive correlation between LUSWE and clinical tests including HRCT and PTF was found. LUSWE may complement the clinical standard HRCT for assessing ILD.

Abstract Aims Cardiac sarcoidosis (CS) often presents with ventricular arrhythmias, heart block, and cardiomyopathy. The prognosis of CS with contemporary management is uncertain. We estimated the impact of baseline and treatment variables on left ventricular ejection fraction (LVEF), ventricular assist device placement, heart transplant, and death. Methods and results We identified patients with CS seen from 1994–2014 at two large academic medical centres. All met the 2014 Heart Rhythm Society expert consensus criteria for diagnosis. From the 574 patients identified, 91 met inclusion criteria. Twenty-two (24.2%) were diagnosed by endomyocardial biopsy. Cardiomyopathy was the primary presentation in 47 patients (51.6%). Within 90 days of diagnosis, 41 patients (45.0%) received prednisone alone, 29 (31.9%) received alternative immunosuppression with or without prednisone, and 21 (23.1%) received no immunosuppression. During follow-up, 31 of 47 cardiomyopathy patients experienced improvement in LVEF, while 23 experienced decline in LVEF or clinical exacerbation, and 15 of 22 patients presenting with ventricular arrhythmia had recurrence. These results did not differ by treatment group. During a median follow-up of 44 months for our cohort, 14 patients reached the composite endpoint of ventricular assist device placement, heart transplant, or death. Survival without the composite outcome did not differ by treatment group, but was worse among patients presenting with cardiomyopathy (log-rank = 0.005). Conclusion In a large series of CS subjects, rates of ventricular arrhythmia and heart failure events remain high with no treatment regimen clearly associated with better outcome. Patients with cardiomyopathy at diagnosis were more likely to reach the composite endpoint.

Purpose: Optimal strategies to detect early interstitial lung disease (ILD) are unknown. ILD is frequently subpleural in distribution and affects lung elasticity. Lung ultrasound surface wave elastography (LUSWE) is a noninvasive method of quantifying superficial lung tissue elastic properties. In LUWSE a handheld device applied at the intercostal space vibrates the chest at a set frequency, and the lung surface wave velocity is measured by an ultrasound probe 5 mm away in the same intercostal space. We explored LUWSE’s ability to detect ILD and correlated LUSWE velocity with physiological, quantitative, and visual radiologic features of subjects with known ILD and of healthy controls. Materials and Methods: Seventy-seven subjects with ILD, mostly caused by connective tissue disease, and 19 healthy controls were recruited. LUSWE was performed on all subjects in 3 intercostal lung regions bilaterally. Comparison of LUSWE velocities pulmonary function testing, visual assessment, and quantitative analysis of recent computed tomographic imaging with Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) software. Results: Sonographic velocities were higher in all lung regions for cases, with the greatest difference in the lateral lower lung. Median velocity in m/s was 5.84 versus 4.11 and 5.96 versus 4.27 (P<0.00001) for cases versus controls, left and right lateral lower lung zones, respectively. LUSWE velocity correlated negatively with vital capacity and positively with radiologist and CALIPER-detected interstitial abnormalities. Conclusions: LUSWE is a safe and noninvasive technique that shows high sensitivity to detect ILD and correlated with clinical, physiological, radiologic, and quantitative assessments of ILD. Prospective study in detecting ILD is indicated.

A lung ultrasound surface wave elastography (LUSWE) technique is developed for assessing interstitial lung disease (ILD). In LUSWE, a 0.1 second harmonic vibration is generated on the chest wall of a subject using a handheld vibrator. An ultrasound probe is aligned with the vibration indenter in the same intercostal region to measure the generated surface wave speed of the lung. A human subject is examined in a sitting position. The lung is tested at the total lung volume. The upper anterior lungs are tested through the second intercostal space in the mid-clavicular line. The lower lateral lungs are tested in the mid-axillary line and the lower posterior lungs are tested in the mid-scapular line. In a prospective clinical study, we measure both lungs through the six intercostal regions for patients and healthy controls. The surface wave speed is measured at 100 Hz, 150 Hz, and 200 Hz. Significant differences of wave speed between patients and controls were found in all lung regions at all frequencies. We also found positive correlation between LUSWE and CT analyses. LUSWE is a safe and noninvasive technique for generating and measuring surface wave propagation on the lung. LUSWE may be useful for assessing ILD.