Preterm birth, defined as delivery before 37 weeks of gestation, represents a global health concern linked to substantial cardiovascular risk later in life. Individuals born preterm, especially at earlier gestational ages, exhibit increased rates of hypertension, heart failure, and ischemic heart disease. The underlying mechanisms include disrupted fetal programming, impaired vascular remodeling, chronic neonatal inflammation, neuroendocrine immaturity, and epigenetic alterations. This review synthesizes current epidemiological evidence from large cohort studies and meta-analyses, integrating mechanistic insights from developmental biology. We discuss distinct prematurity categories—extremely preterm (< 28 weeks), very preterm (28–32 weeks), and moderate to late preterm (33–37 weeks)—highlighting their association with graded cardiovascular risk. Recent findings emphasize the role of non-transmitted parental genes and prenatal environmental toxic metal exposure as additional critical factors influencing fetal cardiovascular programming. A total of 57 articles, identified through a systematic search of PubMed, Embase, and Cochrane databases, were included to address these topics comprehensively. Early identification of preterm-born individuals as a high-risk cardiovascular group is essential for targeted screening, prevention, and interventions from childhood into adulthood. Future studies leveraging multi-omics and epigenetic approaches will further clarify these mechanisms, informing evidence-based guidelines to reduce cardiovascular morbidity associated with preterm birth.

Age-related atrial fibrillation (AF) is a common condition that has yet to be fully understood, with mechanisms to explain its development under investigation. Notably, cellular senescence, cardiac fibrosis, coronary ischemia, cardiac valvular disease, autonomic dysfunction, channelopathies, and immune system remodeling are processes that have been seen to occur with aging and ample evidence has shown their association with the development of AF. Despite robust therapeutic approaches, the incidence of AF continues to rise, suggesting that the dynamic, multi-faceted interactions leading to AF are incompletely understood. One of the newer mechanisms currently being investigated is the gut microbiome. Although more research is needed to understand its impact on the development of age-related AF and targets for therapies, the gut microbiome is a promising new avenue of research that may provide future benefits in AF prophylaxis or enhanced management. As the field works towards developing this knowledge, there are important questions to answer as to the optimal role of potential gut microbiome targeting therapies and their potential risks versus the benefits they provide. This commentary first summarizes the currently understood mechanisms contributing to age-related AF, which is then followed by an analysis of the current work investigating the role of the gut microbiome in the development of age-related AF, and concludes by highlighting notable questions to consider in future work on the role of the gut microbiome and its relationship to age-related AF.

L-Carnitine (LC) is integral to energy production and fatty acid metabolism, facilitating the transport of long-chain fatty acids into mitochondria for β-oxidation. It modulates metabolic pathways, including pyruvate dehydrogenase activity, proteolysis, and protein synthesis, while also having anti-inflammatory and antioxidant characteristics. LC can be commonly applied to win the battle against HIV and cancer cachexia. Also, it can be recruited with the aim of improving physical and cognitive functions in athletes and the elderly. Despite these benefits, long-term LC administration has been associated to cardiovascular risks due its conversion to trimethylamine-N-oxide (TMAO) by the gut microbiota. Elevated TMAO levels are linked to atherosclerosis, oxidative stress, and an increased risk of cardiovascular disease, diabetes, and chronic kidney disease. Managing TMAO levels using dietary treatments and gut microbiota-targeting techniques, such as probiotics, may reduce these risks. This comprehensive review presents the state-of-the-art information on LC’s dual role, emphasizing the balance between its therapeutic potential and the risks of prolonged supplementation. It aims to guide clinicians and researchers in optimizing LC’s benefits while addressing its long term cardiovascular safety concerns.