Rajab, Islam M.

e15520 Background: Fruquintinib is a highly selective tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, which play a critical role in angiogenesis and tumor growth. As a novel anti-angiogenic agent, Fruquintinib has demonstrated promising efficacy in the treatment of various advanced malignancies, including metastatic colorectal cancer. However, concerns about its cardiovascular safety have emerged, given that VEGFR inhibition is often associated with cardiovascular adverse events. Methods: We conducted a systematic search through PubMed, Scopus, Embase, and Web of Science to identify randomized controlled trials and cohort studies that assessed the safety of Fruquintinib compared with placebo in patients with metastatic colorectal and other cancers. The evaluated outcomes included hypertension, coronary artery disease, cerebrovascular accidents, peripheral artery disease, heart failure, thromboembolism, arrhythmias, aortic dissection, and superior vena cava syndrome. Two independent reviewers screened the titles/abstracts based on predefined inclusion and exclusion criteria, followed by a full-text review of potentially relevant studies. Any disagreements between the reviewers were resolved through consultation with a third reviewer to ensure the accuracy and consistency of the study selection. Results: Fifteen reports were included in our study. Out of 3832 patients taking Fruquintinib monotherapy, a total of 997 developed hypertension with a pooled estimate incidence of 0.329 (95% CI: 0.248, 0.410; P < 0.001). In comparison to placebo, Fruquintinib was associated with significantly higher odds of developing hypertension (OR: 6.856; 95% CI: 5.071, 9.268; P < 0.001). Compared to Regorafenib, Fruquintinib demonstrated an OR of 1.549 (95% CI: 0.804, 2.983; P = 0.191) for the development of hypertension. Additionally, patients taking Fruquintinib had a pooled estimate incidence of 0.041 (95% CI: 0.021, 0.060, P < 0.001) for thromboembolism development with an OR of 2.092 (95% CI: 0.813, 5.385; P = 0.126) compared to placebo. Other reported cardiovascular side effects included sinus tachycardia, superior vena cava syndrome, peripheral edema, heart failure, myocardial enzymes elevation, and vascular access complications. Conclusions: Our study found that Fruquintinib is associated with significant cardiovascular risks, with hypertension being the most common adverse event, while thromboembolism did not reach statistical significance. Therefore, close monitoring for treatment-related cardiovascular events should be considered in these patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, is increasingly recognized as a multisystem disorder with significant cardiovascular implications, particularly in its association with atrial fibrillation (AF). As the most common sustained cardiac arrhythmia, AF contributes to substantial morbidity and mortality, making it essential to explore its links with MASLD. The relationship between these conditions is underpinned by shared pathophysiological mechanisms, including systemic inflammation, insulin resistance, oxidative stress, and activation of the renin-angiotensin-aldosterone system. These processes drive atrial remodeling and electrical instability, predisposing individuals with MASLD to AF. Epidemiological studies further support this connection, showing an independent association between MASLD and an increased risk of AF, particularly in those with metabolic comorbidities such as obesity and type 2 diabetes. Beyond increasing AF susceptibility, MASLD may also influence disease progression and response to treatment, affecting anticoagulation safety, rhythm-control strategies, and the success of catheter ablation. Given these clinical implications, therapies targeting metabolic dysfunction—such as statins, renin-angiotensin-aldosterone system inhibitors, and structured lifestyle modifications—may offer dual benefits in mitigating both MASLD and AF risk. However, significant knowledge gaps remain regarding the causal direction of this association, the impact of MASLD severity on AF burden, and the most effective management strategies for patients with both conditions. Future research should prioritize longitudinal studies, mechanistic investigations, and randomized controlled trials to deepen our understanding of this relationship, ultimately guiding more personalized and integrated treatment approaches. Incorporating MASLD screening into cardiovascular risk assessment may enhance early detection and improve outcomes for at-risk populations.

Hyperuricemia, characterized by elevated serum uric acid levels, has been linked to cardiovascular diseases such as hypertension, atrial fibrillation, chronic kidney disease, heart failure, metabolic syndrome, and coronary artery disease. This relationship, however, is complex; while some studies indicate a strong association, others suggest that it may be influenced by confounding factors. The rising global prevalence of hyperuricemia underscores the necessity for a deeper understanding of its cardiovascular implications. Hyperuricemia results from an imbalance in uric acid production and excretion, driven by dietary factors, obesity, insulin resistance, and other conditions. Elevated uric acid levels contribute to cardiovascular risk through mechanisms such as inflammation, oxidative stress, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system. This review highlights the importance of ongoing research to clarify hyperuricemia’s role in cardiovascular disease and suggests that urate-lowering therapies, such as xanthine oxidase inhibitors, may confer cardiovascular benefits; however, evidence remains conflicting. The Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial indicated an increased risk of cardiovascular and all-cause mortality with febuxostat compared with allopurinol, raising safety concerns. In contrast, the Febuxostat versus Allopurinol Streamlined Trial (FAST) demonstrated that febuxostat was noninferior to allopurinol, with even lower all-cause mortality. These opposing findings emphasize the complexity of treatment decisions and the need for individualized management strategies for hyperuricemia. Clinical decisions should consider individual patient risks and characteristics. Ultimately, this comprehensive analysis aims to enhance prevention and management strategies for cardiovascular diseases related to hyperuricemia. The overview includes discussions on major studies such as the Framingham Heart Study, CARES, FAST, PRIZE, and FREED trials, examining their results. It explores whether hyperuricemia is a causal factor versus an associated risk factor and whether it serves as a marker or mediator of disease. Additionally, the review addresses novel biomarkers and predictive models, the management of hyperuricemia in the context of cardiovascular risk, the role of urate-lowering therapies in cardiovascular disease, variability in guidelines and recommendations, and the impact of hyperuricemia in special populations such as those with diabetes and chronic kidney disease. The cardiovascular risk associated with hyperuricemia across various demographics is also discussed. Furthermore, the review suggests that existing risk scores might be modified to include uric acid levels in patients with hyperuricemia.