Introduction:Stroke is a leading cause of morbidity and mortality in Saudi Arabia, with its incidence projected to double by 2030. Diabetes and smoking are major modifiable risk factors. This study assessed their association with stroke type and mortality in a tertiary stroke unit. Methods:We conducted a retrospective review of 336 adults admitted with acute ischemic or hemorrhagic stroke at King Fahad Hospital, Al Ahsa, between January 2023 and December 2024. Demographic characteristics, risk factors, stroke type, and mortality were analyzed using descriptive statistics and multivariable logistic regression. Results:Among 336 patients, 83.9% were younger than 65 years, 66.4% were male, and 86.6% had ischemic stroke. Overall mortality was 4.2%. Diabetes was present in 56.3% of patients, smoking in 21.4%, and both risk factors in 11.3%. Older age (>65 years) was independently associated with hemorrhagic stroke [odds ratio (OR) = 2.29, P = 0.041] and mortality (OR = 4.77, P = 0.013). Non-Saudi nationality was associated with higher odds of hemorrhagic stroke (OR = 2.52, P = 0.014) and mortality (OR = 9.64, P = 0.001). Diabetes independently increased mortality risk (OR = 5.49, P = 0.037). Smoking was not significantly associated with mortality because no deaths occurred among smokers. Conclusion:Ischemic stroke predominated, and mortality was independently associated with older age, non-Saudi nationality, and diabetes. Given the low number of deaths and limited adjustment for confounders, these findings should be interpreted cautiously and validated in larger multicenter setudies.
Metabolic syndrome (MetS) and cardiovascular-kidney-metabolic syndrome represent escalating global health challenges characterized by complex lipid derangements. While traditional lipid panels are standard, the atherogenic index of plasma (AIP) has emerged as a potentially superior marker for capturing the presence of small, dense low-density lipoprotein particles and overall cardiovascular risk. This systematic review evaluates the prognostic value and longitudinal risk prediction of AIP in patients with MetS and related metabolic disorders. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search was conducted across PubMed/MEDLINE, Scopus, Embase, and Web of Science through January 2026. Nine high-quality studies encompassing 197 279 patients were identified. Synthesis of the evidence consistently demonstrates that elevated baseline AIP is consistently and independently associated with major adverse cardiovascular events (hazard ratio: 1.07-1.19), acute myocardial infarction, and cardiovascular death. Longitudinal data reveal that cumulative AIP exposure significantly increases stroke risk (hazard ratio: 2.49) and coronary heart disease. Notably, in patients with diabetic kidney disease, a nonlinear 'U-shaped' association was identified, with a critical inflection point at 0.14, suggesting that both excessively high and low AIP levels correlate with increased mortality. AIP is an accessible and promising biomarker that warrants further comparative validation in predicting long-term cardiometabolic progression. These findings support further evaluation of AIP's role in clinical risk stratification, pending prospective validation and establishment of standardized thresholds across population subgroups.
BACKGROUND:Dilated cardiomyopathy (DCM) is associated with shifts in cardiac metabolism. However, those shifts vary widely across patients, likely reflecting the diverse underlying causes of the disease. Identifying metabolic subtypes, or metabotypes, in DCM patients could help tailor treatments to patient needs. Hence, having a practical approach to identify these metabotypes would be a significant advance toward precision medicine in DCM. METHODS:We present a systems biology approach to uncover metabotypes directly from widely available transcriptomic data. We use in silico metabolic modeling methods that we have optimized for cardiac research to predict metabolic function activities from enzyme expression, followed by a hierarchical clustering approach. To demonstrate its power, we applied our method to publicly available cardiac data from end-stage DCM patients (N=164) and nonfailing controls (N=160). RESULTS:We identified 2 distinct metabotypes in end-stage DCM patients. These metabotypes are characterized by unique metabolic changes, notably in calcium handling, amino acid oxidation, and the pentose phosphate pathway. Strikingly, 1 DCM metabotype showed greater metabolic divergence from healthy controls, suggesting a greater metabolic contribution to its underlying etiology-even though disease severity was similar between the 2 identified DCM metabotypes. Further transcriptome-wide analysis revealed immune-related differences between metabotypes, suggesting an underlying interplay between inflammation, the immune response, and metabolism. CONCLUSIONS:Our results imply the presence of distinct metabotypes in end-stage DCM. Our systems biology approach offers an exciting opportunity to uncover novel insights into DCM, paving the way for a deeper understanding of its progression and heterogeneity.
Cardiovascular outcome trials suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events in individuals with type 2 diabetes (T2DM), but the magnitude of benefit, including recent evidence from the landmark SOUL trial and oral formulations, remains uncertain. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (International Prospective Register of Systematic Reviews ID: CRD420251034652), searching PubMed, Embase, Cochrane CENTRAL, Scopus and ClinicalTrials.gov on 6 May 2025 for randomised controlled trials comparing GLP-1RAs with placebo or usual care in adults with T2DM and established atherosclerotic cardiovascular disease. Seven trials, including 56 191 participants (mean follow-up: 3.5 years), were analysed. GLP-1RAs reduced major adverse cardiovascular events by 11% [hazard ratio: 0.89, 95% confidence interval (CI): 0.83-0.96], all-cause mortality by 11% (hazard ratio: 0.89, 95% CI: 0.82-0.97) and hospitalisation for heart failure by 7% (hazard ratio: 0.93, 95% CI: 0.89-0.98), all with high-certainty evidence. Overall, GLP-1RAs - available in subcutaneous and oral formulations - provide clinically meaningful cardiovascular benefits in high-risk adults with T2DM.
BACKGROUND:Cardiorespiratory fitness (CRF) is a strong predictor of mortality and noncommunicable disease risk, but its underlying molecular mechanisms are poorly understood. In this study, we identified 2 signatures of CRF (1 metabolomic and 1 proteomic) from UK Biobank participants who completed a risk-stratified submaximal cycle ergometer test, with CRF estimated from the heart rate response to incremental workload. METHODS:These signatures were validated in an independent sample of UK participants with data on metabolomics (n=354 222) and proteomics (n=29 961) to investigate prospective associations with all-cause mortality and noncommunicable diseases. Prospective associations were evaluated using Cox proportional hazards models adjusted for age, sex, ethnicity, socioeconomic status, lifestyle factors (including smoking, alcohol intake, diet, and body mass index), and relevant medical history. RESULTS:Our findings reveal that higher CRF is characterized by downregulation of pathways related to inflammation, triglyceride metabolism, glycolysis, and vascular dysfunction, and upregulation of pathways related to cholesterol transport, apolipoprotein particle size, and cytoskeletal remodeling. Leveraging these insights, we developed 2 novel signatures of CRF (1 metabolomic and 1 proteomic) that robustly reflect CRF levels (R2: 0.50-0.60). Over an average of 9 years of follow-up, we observed 27 659 cases of all-cause mortality. Across the discovery and validation cohorts, we found that the metabolomic signature of CRF was strongly associated with a 39% to 54% lower risk of all-cause mortality and markedly reduced risk of type 2 diabetes (90% in both), cardiovascular disease (42%-47%), and colorectal cancer (33%-39%). Additionally, the proteomic signature of CRF was associated with a 17% lower risk of all-cause mortality, and with a 22% to 39% lower risk of type 2 diabetes and cardiovascular disease. CONCLUSIONS:Together, these findings indicate that circulating metabolites and proteins are associated with CRF and with subsequent risk of mortality and noncommunicable diseases.
