The Role of Triglycerides in Atherosclerosis: Recent Pathophysiologic Insights and Therapeutic Implications.

Triglycerides have long been recognized as a cardiovascular disease risk factor. However, their precise role in atherosclerosis and potential utility as a therapeutic target remains debated topics. This review aims to shed light on these aspects by exploring the complex relationship between triglycerides and atherosclerosis from pathophysiological and pharmacological perspectives. Triglycerides, primarily carried by chylomicrons and very low-density lipoproteins, play an essential role in energy storage and utilization. Dysregulation of triglyceride homeostasis and triglyceride- rich lipoproteins metabolism often leads to hypertriglyceridemia and subsequently increases atherosclerosis risk. Triglyceride-rich lipoproteins remnants interact with arterial wall endothelial cells, get retained in the subendothelial space, and elicit inflammatory responses, thereby accelerating atherogenesis. Despite the clear association between high triglyceride levels and increased cardiovascular disease risk, intervention trials targeting triglyceride reduction have produced mixed results. We discuss a range of triglyceride-lowering agents, from fibrates to omega-3 fatty acids, with a focus on their mechanism of action, efficacy, and major clinical trial outcomes. Notably, the role of newer agents, such as angiopoietin-like protein 3 and apolipoprotein C3 inhibitors, is also explored. We highlight the challenges and controversies, including the ongoing debate on the causal role of triglyceride in atherosclerosis and the discordant outcomes of recent clinical trials. The potential confounding effects of associated risk factors, such as elevated apolipoprotein B, insulin resistance, and metabolic syndrome, are considered. In conclusion, this review underscores the importance of a nuanced approach to understanding the role of triglycerides in atherosclerosis and their potential as a therapeutic target. Further research is needed to unravel the complex interplay between triglycerides, triglyceride-rich lipoproteins, and associated factors in atherosclerosis pathogenesis and refine triglyceride-targeted therapeutic strategies.

Echocardiographic Evaluation of Cardiac Masses.

PURPOSE OF REVIEW: Cardiac masses encompass a broad range of etiologies and are often initially revealed by echocardiography. The differential may change depending on the location of the mass and patients' medical history or presentation. It is important for clinicians to be aware of subtle visual characteristics on echocardiography in order to correctly diagnose the pathology. METHODS: Patients who underwent transthoracic echocardiography and were found to have one or more cardiac masses between January 1, 2020, and May 15, 2023, were reviewed. Their demographic data, clinical presentation, medical history, imaging, and follow-up information were collected from hospital electronic medical records, de-identified, and used to complete this review paper. A detailed review of cardiac masses divided by cardiac chamber accompanied by real-world echocardiographic images from patients in a large inner city public hospital. We hope that this systematic review of cardiac masses with real-world echocardiographic images will help clinicians note subtle echocardiographic characteristics to aid in the diagnosis and treatment of cardiac masses.

Tuberculous Pericarditis Presenting as Cardiac Tamponade: Role of Echocardiography.

Tuberculous pericarditis, a rare but potentially lethal manifestation of tuberculosis, poses diagnostic and therapeutic challenges in clinical practice. Its nonspecific clinical presentation often mimics other conditions, leading to delayed or missed diagnoses. We report a 25-year-old male with no past medical history, who presented with nonspecific symptoms such as fatigue, weight loss, body aches, and dyspnea. An electrocardiogram showed low voltage QRS complex with electrical alternans, and transthoracic echocardiography (TTE) showed large pericardial effusion with tamponade physiology with right ventricular diastolic collapse, the collapse of the right atrium and the inferior vena cava was dilated with a respiratory variation of less than 50%. The diagnosis of tuberculous pericarditis was made based on clinical presentation, imaging, and laboratory findings, including a positive QuantiFERON-TB gold test and pericardial fluid analysis, despite negative cultures. This case highlights the significance of considering tuberculosis in the differential diagnosis of pericardial effusion and underscores the role of imaging and laboratory investigations in diagnosis. Management of tuberculous pericarditis involves a combination of antituberculous chemotherapy, pericardiocentesis, and corticosteroids. Despite its rarity, tuberculous pericarditis carries a high mortality rate and can present as cardiac tamponade, as illustrated in our case. This underscores the need for high clinical suspicion, especially in high-risk populations, for timely diagnosis and initiation of treatment.

Cardiac Multimodality Imaging in Hypertrophic Cardiomyopathy: What to Look for and When to Image.

Hypertrophic cardiomyopathy (HCM), now recognized as a common cardiomyopathy of complex genomics and pathophysiology, is defined by the presence of left ventricular hypertrophy of various morphologies and severity, significant hemodynamic consequences, and diverse phenotypic, both structural and clinical, profiles. Advancements in cardiac multimodality imaging, including echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography, with and without angiography have greatly improved the diagnosis of HCM, and enable precise measurements of cardiac mass, volume, wall thickness, function, and physiology. Multimodality imaging provides comprehensive and complementary information and hasemerged as the bedrock for the diagnosis, clinical assessment, serial monitoring, and sudden cardiac death risk stratification of patients with HCM. This review highlights the role of cardiac multimodality imaging in the modern diagnosis and management of HCM.

Statin-Induced Necrotizing Autoimmune Myositis.

Statins are the most frequently prescribed medications for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The United States Preventative Services Task Force recommends that clinicians selectively offer a statin for the primary prevention of ASCVD for adults aged 40 - 75 years with one or more cardiovascular disease risk factors and an estimated 10-year risk of a cardiovascular event of 10% or greater. Despite their ubiquity, it is estimated that approximately 6-10% of patients remain intolerant due to muscle aches. Here, we present a case of a 71-year-old female that was taking atorvastatin for a year and presented to the emergency room with proximal muscle aches and weakness. Laboratory values were significant for an elevated creatinine kinase of 4,166 U/L (reference range, 20 - 180). Her magnetic resonance imaging was significant for edema in bilateral lower extremity proximal muscles. Serology revealed a high anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody, confirming the diagnosis of statin-induced necrotizing autoimmune myositis. A muscle biopsy of the right vastus lateralis revealed necrotic muscle fibers. During her hospital course, she was treated with intravenous methylprednisolone, mycophenolate mofetil, and tacrolimus. Her symptoms gradually improved, and she was discharged after 14 days with a rheumatology follow-up. This is an exceedingly rare complication of statin use and has only recently received increasing attention. Here we present our experience with this disease.

Impact of Aging on Urinary Natriuretic Peptides in Nocturia and Nocturnal Polyuria.

PURPOSE: The pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP. METHODS: Patients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and <65 years old. Urine samples were collected and analyzed for natriuretic peptide (NT-proANP, NT-proBNP, and NT-proCNP) levels. Peptide levels were compared between patients with and without nocturia/NP and within age subgroups; correlation to the NP index (NPi) was determined. RESULTS: Compared to patients without nocturia (N=15), patients with nocturia (N=36) had higher median levels of urinary NT-proANP (15.8 pmol/mmol Cr vs. 10.9 pmol/mmol Cr, P=0.016) and NT-proBNP (6.3 pmol/mmol Cr vs. 4.5 pmol/mmol Cr, P=0.021), but showed no differences in NT-proCNP (2.4 pmol/mmol Cr vs. 2.5 pmol/mmol Cr, P=0.967). Patients ≥65 years old with nocturia had higher NT-proANP (29.8 pmol/mmol Cr vs. 11.0 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 5.0 pmol/mmol Cr, P<0.001) than patients <65 years old. Additionally, patients with NP (N=30) showed higher urinary NT-proANP (19.6 pmol/mmol Cr vs. 10.5 pmol/mmol Cr, P<0.001) and NT-proBNP (6.7 pmol/mmol Cr vs. 4.7 pmol/mmol Cr, P=0.020) compared to patients without NP (N=21). NP patients ≥65 years had higher NT-proANP (29.8 pmol/mmol Cr vs. 12.5 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 4.4 pmol/mmol Cr, P=0.004) than patients <65 years old. NPi positively correlated with urinary NT-proANP (RS=0.417, P=0.002) and NT-proBNP (RS=0.303, P=0.031), but not with NT-proCNP (RS=-0.094, P=0.510). CONCLUSION: Since urinary NT-proANP and NT-proBNP were greater in aged patients with nocturia and NP, natriuretic peptides may contribute to the pathophysiology of these conditions and further research should aim to explore them as targets for management.

Rates and mechanisms of bacterial mutagenesis from maximum-depth sequencing.

In 1943, Luria and Delbrück used a phage-resistance assay to establish spontaneous mutation as a driving force of microbial diversity. Mutation rates are still studied using such assays, but these can only be used to examine the small minority of mutations conferring survival in a particular condition. Newer approaches, such as long-term evolution followed by whole-genome sequencing, may be skewed by mutational 'hot' or 'cold' spots. Both approaches are affected by numerous caveats. Here we devise a method, maximum-depth sequencing (MDS), to detect extremely rare variants in a population of cells through error-corrected, high-throughput sequencing. We directly measure locus-specific mutation rates in Escherichia coli and show that they vary across the genome by at least an order of magnitude. Our data suggest that certain types of nucleotide misincorporation occur 10(4)-fold more frequently than the basal rate of mutations, but are repaired in vivo. Our data also suggest specific mechanisms of antibiotic-induced mutagenesis, including downregulation of mismatch repair via oxidative stress, transcription­replication conflicts, and, in the case of fluoroquinolones, direct damage to DNA.