Shahid Karim

Background: Obstructive sleep apnea (OSA)–chronic obstructive pulmonary disease overlap syndrome has been linked to worse cardiovascular outcomes. Preserved ratio impaired spirometry (PRISm) is recognized as an early stage of chronic obstructive pulmonary diseas. However, whether the coexistence of OSA and PRISm confers increased cardiovascular risk remains unknown. Methods: Using data from the Sleep Heart Health Study, participants were categorized into 4 groups according to OSA and PRISm status. The primary outcome was major adverse cardiovascular and cerebrovascular events. The secondary outcome was cardiovascular disease mortality. Multivariable Cox regression models were used to evaluate the association of these groups with the risk of cardiovascular outcomes. Results: During a median follow‐up of 11.45 years, the incidence of major adverse cardiovascular and cerebrovascular events was 17.00% in non‐OSA with normal lung function, 27.52% in non‐OSA with PRISm, 25.28% in OSA with normal lung function, and 49.40% in OSA with PRISm. After multivariable adjustment, compared with non‐OSA with normal lung function, the adjusted hazard ratios (HRs) for major adverse cardiovascular and cerebrovascular events were 1.20 (95% CI, 0.82–1.75) in non‐OSA with PRISm, 1.04 (95% CI, 0.89–1.21) in OSA with normal lung function, and 1.52 (95% CI, 1.08–2.12) in OSA with PRISm. Corresponding HRs for CVD mortality were 2.02 (95% CI, 1.26–3.24), 1.05 (95% CI, 0.81–1.35), and 2.17 (95% CI, 1.41–3.34), respectively. A significant sex interaction was observed ( P for interaction=0.009), with the association present only in women. Conclusions: The coexistence of OSA and PRISm is independently associated with increased risk of adverse cardiovascular outcomes. This association is observed predominantly in women.

Chronic kidney disease is a major global health burden, and renal fibrosis represents the common pathological endpoint of progressive kidney injury. Fibrosis is driven by complex interactions among injured epithelial cells, activated fibroblasts, endothelial cells, immune cells, and the extracellular matrix, ultimately leading to irreversible loss of renal function. Although animal models and conventional two-dimensional cell cultures have advanced our understanding of fibrogenic mechanisms, their limited human relevance and physiological complexity restrict translational application. Human pluripotent-stem-cell-derived kidney organoids have emerged as promising three-dimensional models that partially recapitulate renal development, nephron-like organization, and multicellular composition. Recent studies have applied kidney organoids to model renal injury and fibrotic remodeling induced by cytokines, hypoxia, nephrotoxins, genetic defects, and metabolic stress. These systems enable investigation of epithelial damage, inflammatory signaling, fibroblast activation, extracellular matrix deposition, and therapeutic responses in a human cellular context. However, current models remain limited by developmental immaturity, incomplete vascularization, lack of urinary drainage, protocol variability, and simplified fibrosis induction. This review summarizes experimental models of renal fibrosis, kidney organoid generation and characterization, organoid-based fibrosis modeling, and future strategies to improve their translational value.

Sleep is an active period of profound autonomic fluctuation, cycling between the parasympathetic dominance of nonrapid eye movement sleep and the sympathetic/parasympathetic volatility of rapid eye movement sleep. Sleep-disordered breathing, a spectrum of disorders marked by recurrent ventilatory instability and intermittent hypoxia during sleep, particularly obstructive sleep apnea, pathologically amplifies this volatility, transforming sleep into a nightly cascade of severe autonomic and hemodynamic stress. The cardinal features of sleep-disordered breathing, intermittent hypoxia, recurrent arousals, and marked intrathoracic pressure swings, act synergistically to drive chronic, 24-hour sympathetic overactivity, chemoreflex sensitization, and maladaptive neuroplasticity. These effects are mediated at a cellular level by oxidative stress, systemic inflammation, endothelial dysfunction, and neuroendocrine dysregulation. This persistent autonomic reset provides a direct mechanistic link to cardiovascular consequences. It is likely a primary driver of hypertension, blunting the nocturnal blood pressure dip and promoting sustained 24-hour sympathoexcitation. It fosters a proarrhythmic substrate for atrial fibrillation through mechanical stress, which drives atrial remodeling and autonomic conflict. Furthermore, sleep-disordered breathing contributes to myocardial ischemia by increasing myocardial oxygen demand and promoting a prothrombotic state. Beyond chronic disease, sleep-related autonomic shifts can act as acute triggers for malignant arrhythmias in individuals with vulnerable substrates, such as inherited channelopathies, a risk that may be significantly amplified by comorbid sleep-disordered breathing. This review delineates the critical neural and cellular pathways connecting sleep, autonomic dysregulation, and cardiovascular risk.

Establishes a robust long-term human adipocyte organoid culture system maintained for over 90 days. Recapitulates key features of OSA-related intermittent hypoxia in human adipocytes in vitro. Demonstrates IH-induced adipocyte aging, including ultrastructural damage and epigenetic reprogramming. Identifies impaired adipogenesis and insulin signaling under intermittent hypoxia. Provides a physiologically relevant platform for mechanistic studies and drug screening.

Background: Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is a well‐established indicator of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). However, its association with electrocardiographic (ECG) abnormalities and the risk of atrial fibrillation (AF) remains uncertain.Objectives: To investigate the association between the presence and burden of LGE with ECG characteristics, including precordial voltage, depolarization and repolarization abnormalities, and the incidence of AF in adults with HCM.Methods: We conducted a retrospective cohort study of 144 adults with HCM with CMR and 12‐lead ECG within 30 days of each other. LGE was quantified as a percentage of LV mass and categorized as absent, < 5%, or ≥ 5%. ECG parameters, including QRS voltage, repolarization abnormalities, and LVH criteria, were analyzed. Incident AF was assessed during a median follow‐up of 6.6 years.Results: LGE was present in 96 (67%) patients, with 21 (22%) having ≥ 5% LGE. There were no significant differences in precordial voltage between patients with and without LGE across Sokolow‐Lyon, Cornell, and Romhilt‐Estes criteria. However, T‐wave inversion was more common in leads I (41% vs. 19%, p = 0.009), aVL (50% vs. 31%, p = 0.033), and V4 (41% vs. 23%, p = 0.035) in patients with LGE. Patients with ≥ 5% LGE had a significantly lower median LVEF (64% vs. 74%, p = 0.003). Additionally, LGE presence was not associated with an increased risk of incident AF (HR 1.8, 95% CI 0.6–5.3, p = 0.308).Conclusion: In contrast to pediatric HCM, LGE is associated with specific ECG repolarization abnormalities, particularly T‐wave inversion in lateral leads, but does not significantly affect precordial voltage in adults.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and sleep disordered breathing (SDB) is a treatable risk factor that has been seen to occur concurrently, and is known to propagate mortality and morbidity in a number of cardiovascular disease states including heart failure, and indeed hypertrophic cardiomyopathy. In this review, we summarize past studies that explored the simultaneous occurrence of HCM and SDB, and the pathophysiology of SDB in relation to heart failure, arrhythmias, cardiac ischemia and pulmonary hypertension in HCM. The current therapeutic modalities, with the effect of obstructive sleep apnea (OSA) treatment on HCM, are then discussed along with potential future directions.