Circular RNAs (circRNAs) have emerged as crucial cardiovascular regulators through gene expression modulation, microRNA sponging, and protein interactions. Their covalently closed structure confers exceptional stability, making them detectable in blood and tissues as potential biomarkers. This review explores current research examining circRNAs across cardiovascular diseases, including atherosclerosis, myocardial infarction, and heart failure. We highlight the control that circRNA exerts over endothelial function, smooth muscle switching, inflammatory recruitment, and cardiomyocyte survival. Key findings distinguish frequently disease-promoting circRNAs (circANRIL, circHIPK3) from context-dependent regulators (circFOXO3). Compartment-specific controllers include endothelial stabilizers (circGNAQ), smooth muscle modulators (circLRP6, circROBO2), and macrophage regulators (circZNF609), functioning as tunable rheostats across vascular compartments. Overall, the literature suggests that circRNAs represent promising tools in two translational avenues: (i) blood-based multimarker panels for precision diagnosis and (ii) targeted modulation of pathogenic circuits. Clinical translation will require precise cell-type targeting, efficient delivery to cardiovascular tissues, and rigorous mitigation of off-target effects.

Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as T2D. To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2Dparticipants from the Eastern Province of Saudi Arabia. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples based on diabetes status and glucose level. We observed overall positive enrichment within diabetics compared to healthy individuals and amongst diabetic participants; those with high glucose levels exhibited slightly more positive enrichment compared to those at lower risk of fasting hyperglycemia. In particular, the genus Firmicutes was upregulated in diabetic participants compared to non-diabetic participants, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. Based on diabetes status and glucose levels of Saudi participants, relatively stable differences in stool composition were perceived by differential abundance and alpha diversity measures. Author summary: The rates of Type 2 diabetes (T2D) in Saudi Arabia have risen dramatically in the last several decades due to socio-economic changes resulting in changes in dietary and sedentary lifestyles. This emergence has grown more rapidly and affects larger proportions of the population with estimates of T2D prevalence impacting 25% of the population. There is a paucity of microbiome data from Middle Eastern populations, and previous studies have been conducted on small sample sizes. Here we report on the first-ever characterization of gut microbiota T2D versus non-T2D and largest microbiome study ever conducted in a Middle Eastern country. The datasets from this study are important to create a regional reference T2D-microbiome catalogue which will propel the understanding of regional gut flora which are associated with T2D development. Based on T2D status and quantified glucose levels of Middle Eastern participants, relatively stable differences in stool composition were observed by differential abundance and alpha diversity measures. Comparing overlapping and varying patterns in gut microbiota with other studies is critical to assessing novel treatment options in light of a rapidly growing T2D health epidemic.

Left main (LM) coronary artery disease accounts for approximately 4–6% of all percutaneous coronary interventions (PCIs). There has been mounting evidence indicating the non-inferiority of LM PCI as a revascularization option, particularly for those with a low SYNTAX score. The EXCEL and NOBEL trials have shaped current guidelines. The European Society of Cardiology assigned a class 2a level of evidence B for isolated LM disease involving the shaft and ostium and a class IIb level of evidence B for isolated LM disease involving the bifurcation or additional two- or three-vessel disease and a SYNTAX score <32. However, data on the use of a single stent or an upfront two-stent strategy for distal LM disease are conflicting, wherein the EBC Main trial reported similar outcomes with a stepwise provisional approach and the DKCRUSH-V trial reported better outcomes with an upfront two-stent strategy using the ‘double-kissing’ crush technique. Although several studies have noted better immediate results with image-guided PCI, there are few data on outcomes in LM disease specifically. In fact, the uptake of imaging in the aforementioned landmark trials was only 40%. More importantly, the role of mechanical circulatory support (MCS) has been less well studied in LM PCI. Indiscriminate use of MCS for LM PCI has been noted in clinical practice. Trials evaluating the benefit of MCS in high-risk PCI demonstrated no benefit. This review highlights contemporary trials as they apply to current practice in LM PCI.

Spontaneous coronary artery dissection is becoming an important cause of acute coronary syndrome, particularly among young women. Its association with female gender, pregnancy, and postpartum period and emotional stress differentiate it from atherosclerotic heart disease. In recent years, there has been more awareness and improved diagnostic and management capabilities, which in turn has increased the diagnostic yield, although knowledge gaps remain. In the present case, a 36-year-old female, who was at 1-month postpartum period, presented with ventricular fibrillation and cardiac arrest. The clinical course was associated with pulmonary hemorrhage. The patient had no current atherosclerotic risk factors, only a family history of sudden cardiac arrest in her mother and sister. She underwent a coronary angiogram, which revealed spontaneous coronary artery dissection (SCAD) in both the left anterior descending and left circumflex artery. Percutaneous coronary intervention was performed but the clinical course was associated with pulmonary hemorrhage. Bronchopulmonary lavage was performed as a diagnostic and therapeutic intervention, and she was discharged in good health. SCAD is an important differential diagnosis in young females presenting with acute coronary syndrome or cardiac arrest. Early recognition and diagnosis are important to decrease the high mortality rate of this disease.

Plasma circular RNAs (circRNAs) are stable RNA molecules found in blood, which makes them potential noninvasive biomarkers for acute myocardial infarction (MI). The aim of this study was to describe the plasma circRNA profile in patients with acute MI and to identify circRNA markers that may help detect heart injury and reflect the biological processes involved. We compared plasma samples from patients with acute MI and healthy controls using total RNA sequencing with unique molecular identifiers (UMIs). After sequencing, reads were processed through quality control, alignment, duplicate removal, and circRNA detection. Differential expression was analyzed after adjusting for age, sex, smoking, and technical factors. Several circRNAs were significantly different between MI cases and controls and were able to separate the two groups in principal component and receiver operating characteristic analyses. Among the most increased circRNAs were hsa-PASK_0004, hsa-STXBP3_0002, hsa-RCAN3_0002, and hsa-RANBP9_0044, while hsa-HIF1A_0002, hsa-SUZ12_0049, hsa-PNRC1_0001, and hsa-RAB2A_0002 were decreased. Several candidates showed AUC values above 0.7. Pathway analysis linked the host genes of these circRNAs to inflammation, platelet activation, coagulation, and cardiomyocyte stress responses. Overall, these findings suggest that circulating circRNAs may serve as useful blood-based markers of MI and provide insight into the molecular changes that accompany acute MI.

Background: Stroke remains a leading cause of death and long-term disability worldwide. Sleep disturbances are increasingly recognized as potential factors influencing recovery after stroke. Therefore, in this study we examined the associations of sleep disturbances and metabolic markers with post-stroke outcomes. Methods: We conducted a retrospective study of adult patients with stroke-related presentations. The primary analysis included 270 patients with follow-up mRS data. Extracted variables included demographics, vascular risk factors, stroke subtype, imaging findings, sleep features, and selected laboratory markers. Functional outcome was classified as favorable, mRS 0–2, or unfavorable, mRS 3–6. Recurrent stroke burden was analyzed as 0–1 versus ≥2 documented events. Associations and predictive performance were assessed using group comparisons, LASSO logistic regression, and random forest models with repeated 10-fold cross-validation. Results: Among 270 stroke patients, 214 (79.3%) had favorable outcomes and 56 (20.7%) had unfavorable outcomes. Sleep disturbances were common, especially nocturnal awakenings (59.6%), increased sleep apnea risk (44.4%), circadian rhythm disturbances (28.9%), and insomnia (23.7%). Unfavorable outcomes were linked to older age, cardio-aortic embolism, large vessel/cortical stroke, abnormal vascular imaging, insomnia, and lower HDL. In LASSO analysis, age, steno-occlusive/atherosclerotic imaging, cardio-aortic embolism, and insomnia predicted unfavorable outcome, while HDL was protective. For recurrent stroke, small artery occlusion and hypertension with diabetes were retained. In predictive modeling, the best random forest model showed good discrimination AUC values of 0.791 ± 0.0126. Conclusions: Poorer stroke outcomes were associated with vascular factors, insomnia, and low HDL; recurrent events were mainly associated with small artery occlusion.