Butler, Javed

Background: Chronic kidney disease (CKD) has been linked to elevated inflammatory biomarkers, yet few studies have evaluated these associations using iothalamate-based measures of kidney function, highlighting the need for further research. Research question: Is CKD associated with elevated inflammatory markers when defined by measured glomerular filtration rate (mGFR) and urinary albumin-to-creatinine ratio (UACR)? Methods: Participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort were included if they had data available for at least one inflammatory marker at visit 2. 17 inflammatory markers were assessed, including C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), serum amyloid A, intercellular and vascular adhesion molecules (ICAM, VCAM), E-selectin, P-selectin, monocyte chemoattractant protein (MCP), myeloperoxidase (MPO), receptor for advanced glycation end products (RAGE), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2). Kindey function was assessed using the urinary clearance of iothalamate. CKD was defined as mGFR < 60 mL/min/1.73 m 2 or UACR ≥ 30 mg/g. To further assess whether associations persisted without albuminuria, we also defined CKD solely by mGFR < 60 mL/min/1.73 m 2 . Generalized estimating equations (GEE) were used to assess associations between CKD status and inflammatory markers, accounting for familial clustering. Exponentiated beta coefficients from GEE models were used to present geometric mean (GM) ratios of each biomarker by CKD status, adjusted for demographics, lifestyle factors, cardiovascular risk factors, and medication use. Results: Among 1,010 participants (mean age 61 ± 10 years; 67% women; 48% Black adults), 207 were classified as having CKD. After adjusting for potential confounders, individuals with CKD had significantly higher levels of hsCRP, VCAM, TNFR1, and TNFR2 compared to those without CKD (GM ratios > 1; p < 0.05), while the remaining inflammatory markers showed no significant differences ( Figure 1 ). Importantly, these elevations remained significant when CKD was defined by mGFR alone ( Figure 2 ). Conclusion: Our findings suggest that CKD, defined by mGFR, is associated with specific inflammatory biomarkers, underscoring the need for mechanistic studies to investigate these associations.

Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased risk of diabetic retinopathy (DR) and nonarteritic anterior ischemic optic neuropathy (NAION). The risk of sight-threatening complications associated with GLP-1 RAs is underexamined. Objective To investigate whether the use of GLP-1 RAs in patients with T2D is associated with the development of DR, NAION, or DR complications. Design, Setting, and Participants This retrospective cohort study of adults (aged ≥18 years) with T2D and a recent hemoglobin A 1c level of 6.5% or higher was conducted between January 1, 2015, and September 30, 2022, using the TriNetX database. The cohort was divided into 2 groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals received prescriptions for a GLP-1 RA. The statistical analysis was conducted on October 10, 2024. Exposures At least 2 prescriptions of a GLP-1 RA given 6 months apart. Main Outcomes and Measures Cox proportional hazard regression models were used to evaluate the primary outcome: association between GLP-1 RAs and the risk of incident DR, NAION, or sight-threatening complications over a 2-year follow-up period. Results After PSM, 185 066 individuals (mean [SD] age, 59.0 [12.5] years; 93 389 females [50.5%]) were prescribed GLP-1 receptor agonists. Use of GLP-1 RAs was associated with an increased incidence of DR (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11), while no statistically significant difference was observed in the risk of NAION (HR, 1.26; 95% CI, 0.94-1.70). In a subgroup analysis of 32 695 patients with preexisting DR, GLP-1 RAs were not associated with progression to proliferative DR (HR, 1.06; 95% CI, 0.97-1.15) or diabetic macular edema (HR, 0.98; 95% CI, 0.95-1.01) but were associated with a lower occurrence of vitreous hemorrhages (HR, 0.74; 95% CI, 0.68-0.80), neovascular glaucoma (HR, 0.78; 95% CI, 0.68-0.88), or blindness (HR, 0.77; 95% CI, 0.73-0.82). Conclusions and Relevance In this cohort study of individuals with T2D, GLP-1 RA use was associated with a modestly increased risk of incident DR; however, fewer patients experienced sight-threatening DR complications, including blindness, even among those with preexisting DR. These findings suggest that all patients with T2D treated with GLP-1 RAs, regardless of preexisting DR, should be regularly screened and monitored for potential complications of T2D.

Abstract Heart failure with reduced or preserved ejection fraction is associated with elevated left atrial pressure at rest due to fluid overload or during exercise, leading to pulmonary venous congestion. Even with available treatments, heart failure hospitalizations remain high, and improvements in quality-of-life scores and functional capacity are modest. Thus, there is growing interest in non-pharmacological methods to decompress the left atrium and improve heart failure symptoms and outcomes. Left-to-right shunts have emerged as a potential therapeutic option to reduce left atrial hypertension, improve quality of life, and impact long-term outcomes. This nascent field carries both potential therapeutic promise and many unanswered questions. Recent data have questioned whether the effects of this therapy vary based on the left ventricular ejection fraction, pulmonary vascular resistance, and/or right ventricular structure and function. This review discusses the basis for left-to-right shunt therapies, synthesizes past and ongoing clinical trials, and offers future directions.

Background We sought to study the prevalence of high‐sensitivity troponin and its association with cardiac structure and outcomes in ambulatory and hospitalized patients with heart failure with a preserved ejection fraction ( HF p EF ). Methods and Results A post hoc analysis utilized data from HF p EF patients: DOSE (Diuretic Optimization Strategies Evaluation) and CARRESS ‐ HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) enrolled patients hospitalized with acute HF p EF , and RELAX (Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) enrolled ambulatory patients with HF p EF . High‐sensitivity troponin I (hs‐TnI) was measured in hospitalized patients at baseline, at 72 to 96 hours, on day 7, and on day 60. In ambulatory patients hs‐TnI was measured at baseline and at week 24. In the ambulatory cohort, correlations between hs‐TnI and cardiac structure and function were assessed. The association between hs‐TnI and a 60‐day composite of emergency room visits, readmissions, and death was assessed for hospitalized patients using multivariable Cox proportional hazard models. The study population included 139 hospitalized and 212 ambulatory patients with HF p EF and hs‐TnI measured at baseline. The median (25th, 75th percentiles) baseline troponin was 17.6 (11.1, 41.0) ng/L in hospitalized patients and 9.5 (5.3, 19.7) ng/L in ambulatory patients ( P <0.001). The prevalence of elevated hs‐TnI (>99% percentile upper reference limit was 86% in hospitalized patients and 53% among ambulatory patients, with stable elevation in ambulatory patients during follow‐up. HF p EF patients with a hs‐TnI above the median were older with worse left ventricular hypertrophy and diastolic dysfunction. Continuously valued hs‐TnI (per doubling) was associated with increased risk of composite end point (adjusted hazard ratio 1.20, 95% confidence interval 1.00‐1.43; P =0.042). Conclusions Hs‐TnI is commonly elevated among both hospitalized and ambulatory patients with HF p EF . Increased hs‐TnI levels are associated with worse cardiac structure and increased risk of adverse events.