The Role of Microbial Metabolites in the Progression of Neurodegenerative Diseases-Therapeutic Approaches: A Comprehensive Review.

The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood-brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.

Implications of Butyrate Signaling Pathways on the Motor Symptomatology of Parkinson's Disease and Neuroprotective Effects-Therapeutic Approaches: A Systematic Review.

Parkinson's Disease (PD) is a prevalent neurodegenerative disorder characterized by motor and non-motor symptoms. Emerging evidence suggests that gut microbiota alterations, specifically involving short-chain fatty acids (SCFAs) like butyrate, may influence PD pathogenesis and symptomatology. This Systematic Review aims to synthesize current research on the role of butyrate in modulating motor symptoms and its neuroprotective effects in PD, providing insights into potential therapeutic approaches. A systematic literature search was conducted in April 2024 across databases, including ScienceDirect, Scopus, Wiley, and Web of Science, for studies published between 2000 and 2024. Keywords used were "neuroprotective effects AND butyrate AND (Parkinson disease OR motor symptoms)". Four authors independently screened titles, abstracts, and full texts, applying inclusion criteria focused on studies investigating butyrate regulation and PD motor symptoms. A total of 1377 articles were identified, with 40 selected for full-text review and 14 studies meeting the inclusion criteria. Data extraction was performed on the study population, PD models, methodology, intervention details, and outcomes. Quality assessment using the SYRCLE RoB tool highlighted variability in study quality, with some biases noted in allocation concealment and blinding. Findings indicate that butyrate regulation has a significant impact on improving motor symptoms and offers neuroprotective benefits in PD models. The therapeutic modulation of gut microbiota to enhance butyrate levels presents a promising strategy for PD symptom management.

High-Risk Histopathological Features of Retinoblastoma following Primary Enucleation: A Global Study of 1426 Patients from 5 Continents.

PURPOSE: To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents. METHODS: Retrospective study of 1426 primarily enucleated RB eyes from five continents. RESULTS: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients. CONCLUSION: There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.

Comparative Analysis of Academic, Behavioral, and Psychophysiological Variables in Male and Female Vocational Training Students.

BACKGROUND/OBJECTIVES: The purpose of this study was to investigate whether or not there are notable differences between male and female vocational training students in terms of academic, behavioral, and psychophysiological characteristics. METHODS: A total of 411 vocational training students, 210 of whom were male and 201 of whom were female, participated in an online survey that assessed academic, behavioral, and psychophysiological patterns. RESULTS: In terms of extraversion and openness to experience, our research revealed that no statistically significant differences were noticed. When it came to agreeableness, however, significant differences were seen, with female students getting higher marks than male students. Furthermore, we found that there were significant gender differences in terms of neuroticism and conscientiousness, with female students achieving higher scores than male students. When compared to their male counterparts, females displayed higher performance in terms of academic success. They also demonstrated superior values in terms of reported stress, anxiety, and cognitive inflexibility. CONCLUSIONS: The findings of this study provide a more in-depth understanding of the numerous factors that have an impact on students engaging in vocational training. This will serve as a foundation for the development of individualized instructional and support programs.

Differences in the Evaluation of Malnutrition and Body Composition Using Bioelectrical Impedance Analysis, Nutritional Ultrasound, and Dual-Energy X-ray Absorptiometry in Patients with Heart Failure.

BACKGROUND: Although malnutrition is frequently observed in patients with heart failure (HF), this diagnosis should be performed carefully since HF itself is associated with increased inflammatory activity, which affects body weight, functionality, and some nutritional parameters; thus, its isolated interpretation can erroneously identify surrogate markers of severity as markers of malnutrition. In this context, we aimed to evaluate the prevalence of malnutrition using different classification systems and perform a comprehensive nutritional evaluation to determine the reliability of different diagnostic techniques. PATIENTS AND METHODS: Eighty-three patients with a recent hospital admission due to HF were evaluated. GLIM diagnosis criteria and subjective global assessment (SGA) were performed; a comprehensive anthropometric, functional, and biochemical nutritional evaluation was performed, in which bioelectrical impedance analysis (BIA), nutritional ultrasound, and dual-energy X-ray absorptiometry (DXA) were performed. Additionally, mortality and additional admissions due to HF were determined after a mean follow up of 18 months. RESULTS: Malnutrition according to the GLIM criteria (54%) accurately distinguished patients with impaired functionality, lower lean mass, skeletal mass index, and appendicular muscle mass (BIA), as well as lower trunk fat mass, trunk lean mass, fat-free mass (DXA), and decreased albumin and increased C-reactive protein serum levels. According to SGA, there were significant changes in body composition parameters determined by BIA, muscle ultrasound, and functional tests between well-nourished patients and patients with risk of malnutrition (53.7%) or who had malnutrition (7.1%), but not when the last two groups were compared. BIA and DXA showed strong correlations when evaluating muscle and fat mass in HF patients, but correlations with nutritional ultrasound were limited, as well as functional tests. A multivariate analysis showed that no significant association was observed between body composition and mortality, but preperitoneal fat was associated with an increased risk of new hospital admissions (OR: 0.73). CONCLUSIONS: GLIM criteria identified a lower percentage of patients with HF and malnutrition compared with SGA; thus, SGA could have a role in preventing malnutrition in HF patients. Nutritional evaluation with BIA and DXA in patients with HF showed reliable results of body composition parameters in HF, and both help with the diagnosis of malnutrition according to the GLIM or SGA criteria and could provide complementary information in some specific cases.

Psychological characteristics associated with chemsex among men who have sex with men: Internalized homophobia, conscientiousness and serostatus as predictive factors.

Background: Although significant progress has been made in the rights of the LGBTQ+ community, even today this population still faces stigma and discrimination that impacts their mental health. In the case of men who have sex with men, it has been demonstrated that the use of drugs in a sexual context (chemsex) is one of the coping mechanisms and means of escape to deal with these situations. Method: We assessed 284 native Spanish speakers' participants, 45,4 % were not engaged in sexualised drug use (n = 129) while 54,6 % were chemsex users (n = 155) using 18,7 % of them the injected via. The participants completed six questionnaires about life and sexual satisfaction, depression, anxiety, internalised homophobia and personality. Bivariate and multivariable logistic regression were performed to assess the associations between sexual behaviour-related and psychological variables. Kruskal-Wallis H test was used to analysed the impact on mental health of the administration via. Results: Aged, unprotected sexual relationships, positive serostatus, homonegativity and conscientiousness predicted the chemsex engagement. Furthermore, we found differences regarding the administration via. Conclusions: We conclude that mental health significantly correlates with the practice of chemsex, highlighting the importance of integrating mental health considerations into the prevention of risky sexual behaviors.

The Interplay of Sports and Nutrition in Neurological Health and Recovery.

This comprehensive review explores the dynamic relationship between sports, nutrition, and neurological health. Focusing on recent clinical advancements, it examines how physical activity and dietary practices influence the prevention, treatment, and rehabilitation of various neurological conditions. The review highlights the role of neuroimaging in understanding these interactions, discusses emerging technologies in neurotherapeutic interventions, and evaluates the efficacy of sports and nutritional strategies in enhancing neurological recovery. This synthesis of current knowledge aims to provide a deeper understanding of how lifestyle factors can be integrated into clinical practices to improve neurological outcomes.

Personalizing Nutrition Strategies: Bridging Research and Public Health.

In recent years, although life expectancy has increased significantly, non-communicable diseases (NCDs) continue to pose a significant threat to the health of the global population. Therefore, eating habits have been recognized as key modifiable factors that influence people's health and well-being. For this reason, it is interesting to study dietary patterns, since the human diet is a complex mixture of macronutrients, micronutrients, and bioactive compounds, and can modulate multiple physiological processes, including immune function, the metabolism, and inflammation. To ensure that the data we acquired were current and relevant, we searched primary and secondary sources, including scientific journals, bibliographic indexes, and databases in the last 15 years with the most relevant articles. After this search, we observed that all the recent research on NCDs suggests that diet is a critical factor in shaping an individual's health outcomes. Thus, cardiovascular, metabolic, mental, dental, and visual health depends largely on the intake, habits and patterns, and nutritional behaviors. A diet high in processed and refined foods, added sugars, and saturated fats can increase the risk of developing chronic diseases. On the other hand, a diet rich in whole, nutrient-dense foods, such as vegetables, fruits, nuts, legumes, and a high adherence to Mediterranean diet can improve health's people.

Lactiplantibacillus (Lactobacillus) plantarum as a Complementary Treatment to Improve Symptomatology in Neurodegenerative Disease: A Systematic Review of Open Access Literature.

This systematic review addresses the use of Lactiplantibacillus (Lactobacillus) plantarum in the symptomatological intervention of neurodegenerative disease. The existence of gut microbiota dysbiosis has been associated with systemic inflammatory processes present in neurodegenerative disease, creating the opportunity for new treatment strategies. This involves modifying the strains that constitute the gut microbiota to enhance synaptic function through the gut-brain axis. Recent studies have evaluated the beneficial effects of the use of Lactiplantibacillus plantarum on motor and cognitive symptomatology, alone or in combination. This systematic review includes 20 research articles (n = 3 in human and n = 17 in animal models). The main result of this research was that the use of Lactiplantibacillus plantarum alone or in combination produced improvements in symptomatology related to neurodegenerative disease. However, one of the studies included reported negative effects after the administration of Lactiplantibacillus plantarum. This systematic review provides current and relevant information about the use of this probiotic in pathologies that present neurodegenerative processes such as Alzheimer's disease, Parkinson's disease and Multiple Sclerosis.

Sporting Mind: The Interplay of Physical Activity and Psychological Health.

The symbiotic relationship between sports practice and psychological well-being has, in recent times, surged to the forefront of academic and public attention. The aim of this narrative review is to comprehensively explore the intricate pathways linking physical engagement in sports to its subsequent impacts on mental health and synthesize the multifarious effects of sports on psychological health, offering insights for integrating physical and psychological strategies to enhance well-being. From neurobiological underpinnings to therapeutic applications, this comprehensive manuscript provides an in-depth dive into the multifaceted world of sports and psychology. Highlighting evidence-based interventions, this review aspires to offer actionable insights for practitioners, athletes, and individuals alike, advocating for a holistic approach to mental well-being. This manuscript highlights the profound impact of sports on mental health, emphasizing its role in emotional regulation, resilience, cognitive function, and treating psychological conditions. It details how sports induce neurochemical changes, enhance brain functions like memory and learning, and aid against cognitive decline. This review also notes the benefits of regular exercise in mood improvement, stress management, and social skill enhancement, particularly when combined with mindfulness practices. It underscores the importance of considering cultural and gender perspectives in sports psychology, advocating for an integrated physical-psychological approach to promote overall well-being.

Corrigendum: Deep brain stimulation neuromodulation for the treatment of mood disorders: obsessive compulsive disorder and treatment resistant depression.

[This corrects the article DOI: 10.3389/fpsyt.2021.764776.].

Basis of preventive and non-pharmacological interventions in asthma.

Asthma is one of the most common atopic disorders in all stages of life. Its etiology is likely due to a complex interaction between genetic, environmental, and lifestyle factors. Due to this, different non-pharmacological interventions can be implemented to reduce or alleviate the symptoms caused by this disease. Thus, the present narrative review aimed to analyze the preventive and non-pharmacological interventions such as physical exercise, physiotherapy, nutritional, ergonutritional, and psychological strategies in asthma treatment. To reach these aims, an extensive narrative review was conducted. The databases used were MedLine (PubMed), Cochrane (Wiley), Embase, PsychINFO, and CinAhl. Asthma is an immune-mediated inflammatory condition characterized by increased responsiveness to bronchoconstrictor stimuli. Different factors have been shown to play an important role in the pathogenesis of asthma, however, the treatments used to reduce its incidence are more controversial. Physical activity is focused on the benefits that aerobic training can provide, while physiotherapy interventions recommend breathing exercises to improve the quality of life of patients. Nutritional interventions are targeted on implement diets that prioritize the consumption of fruits and vegetables and supplementation with antioxidants. Psychological interventions have been proposed as an essential non-pharmacological tool to reduce the emotional problems associated with asthma.

Validation of Modaplex POLE mutation assay in endometrial carcinoma.

The TCGA-based molecular classification of endometrial cancer has emerged as an important tool to stratify patients according to prognosis. A simplified scheme has been proposed, by using immunohistochemistry for p53, MSH6, and PMS2 and a molecular test for POLE mutations (NGS or Sanger sequencing, techniques that are not available in many centers worldwide). In this study, we validate a novel method that allows simultaneous analysis of multiple pathogenic POLE mutations. The Modaplex technology integrates polymerase chain reaction and capillary electrophoresis. The design of this study encompassed 4 different steps: (1) a retrospective-pilot phase, with 80 tumors, balancing the four molecular subgroups. (2) A retrospective phase of 25 tumors obtained between 2016 and 2020, and 30 tumors obtained between 2000 and 2015. (3) An inter-laboratory corssavalidation step with 19 cases (belonging to phases 1 and 2). (4) A prospective cohort of 123 tumors, of unknown POLE status, with simultaneous validation by Sanger sequencing. A total of 258 samples were analyzed. In the first and second phases, the test showed positive/negative predictive values of 100%, by correctly identifying POLE mutation status in 79/79 and 55/55 cases. Phase 3 showed 100% of inter-laboratory consistency. Phase 4 showed 16 positive samples out of the 123 prospective cases. Overall, the test has revealed sensitivity and specificity of 100%, identifying a total of 47 POLE-mutated tumors. We have shown that this technique allows faster and easier identification of multiple pathogenic POLE mutations with high robustness and confidence when comparing to other tests such as Sanger sequencing.

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach-A Comprehensive Narrative Review.

The comprehensive narrative review conducted in this study delves into the mechanisms of communication and action at the molecular level in the human organism. The review addresses the complex mechanism involved in the microbiota-gut-brain axis as well as the implications of alterations in the microbial composition of patients with neurodegenerative diseases. The pathophysiology of neurodegenerative diseases with neuronal loss or death is analyzed, as well as the mechanisms of action of the main metabolites involved in the bidirectional communication through the microbiota-gut-brain axis. In addition, interventions targeting gut microbiota restructuring through fecal microbiota transplantation and the use of psychobiotics-pre- and pro-biotics-are evaluated as an opportunity to reduce the symptomatology associated with neurodegeneration in these pathologies. This review provides valuable information and facilitates a better understanding of the neurobiological mechanisms to be addressed in the treatment of neurodegenerative diseases.

Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities.

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated in the pathogenesis of various brain diseases, including neurodegenerative disorders, stroke, and psychiatric illnesses. This review paper provides a comprehensive overview of the intricate relationship between mitochondria and brain disease, focusing on the underlying pathological mechanisms and exploring potential therapeutic opportunities. The review covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, mitochondrial dynamics, calcium dysregulation, and reactive oxygen species generation in the context of brain disease. Additionally, it discusses emerging strategies targeting mitochondrial dysfunction, including mitochondrial protective agents, metabolic modulators, and gene therapy approaches. By critically analysing the existing literature and recent advancements, this review aims to enhance our understanding of the multifaceted role of mitochondria in brain disease and shed light on novel therapeutic interventions.

Impact of reflex locomotion and the Bobath concept on clinical and biomolecular parameters in people with multiple sclerosis: study protocol for a randomized controlled trial.

Introduction: Multiple sclerosis (MS) is a progressive disease with a fluctuating and unpredictable course that has no curative treatment at present. One of its main characteristics is the variety of signs and symptoms that produce a high percentage of patients who present alterations in balance and gait during the development of the disease, decreased muscle strength, spasticity, or decreased pimax. Rehabilitative therapy, especially physiotherapy, is the main course of the treatment of these alterations using reflex locomotion and the Bobath concept as a form of kinesitherapy that activates the preorganized circuits of the central nervous system. Objective: The objective of this study is to evaluate the reflex locomotion and Bobath concept effects on balance, spasticity, reaction time, respiratory parameters, and lacrimal biomolecular markers. Methods and analysis: This is a randomized controlled trial on the effectiveness of two neurorehabilitation techniques in patients with multiple sclerosis conducted at the University of Salamanca. The research will take place at the Faculty of Nursing and Physiotherapy, University of Salamanca. The study will be conducted from June 2023 to June 2024. The reflex locomotion group will receive individual sessions of therapy (n = 27), and the Bobath concept group (n = 27) will receive the same number of sessions. Both groups will receive two sessions per week for 12 months. The measurement variables will be the Berg Balance Scale, the Tardieu Scale, the Cognitfit Program, Maximum Inspiratory Pressure, and Lacrimal Biomarkers. Ethics and dissemination: This study has been approved by the Ethics Committee of the University of Salamanca on March 2023 (ref: 896). Limitations: The main limitations of this study are the selection and number of patients, the delay in implementing the therapy within the initially scheduled period, inadequate sample collection, and inadequate sample processing. Trial registration number: ClinicalTrials.gov; identifier: NCT05558683.

Neuro-Vulnerability in Energy Metabolism Regulation: A Comprehensive Narrative Review.

This comprehensive narrative review explores the concept of neuro-vulnerability in energy metabolism regulation and its implications for metabolic disorders. The review highlights the complex interactions among the neural, hormonal, and metabolic pathways involved in the regulation of energy metabolism. The key topics discussed include the role of organs, hormones, and neural circuits in maintaining metabolic balance. The review investigates the association between neuro-vulnerability and metabolic disorders, such as obesity, insulin resistance, and eating disorders, considering genetic, epigenetic, and environmental factors that influence neuro-vulnerability and subsequent metabolic dysregulation. Neuroendocrine interactions and the neural regulation of food intake and energy expenditure are examined, with a focus on the impact of neuro-vulnerability on appetite dysregulation and altered energy expenditure. The role of neuroinflammation in metabolic health and neuro-vulnerability is discussed, emphasizing the bidirectional relationship between metabolic dysregulation and neuroinflammatory processes. This review also evaluates the use of neuroimaging techniques in studying neuro-vulnerability and their potential applications in clinical settings. Furthermore, the association between neuro-vulnerability and eating disorders, as well as its contribution to obesity, is examined. Potential therapeutic interventions targeting neuro-vulnerability, including pharmacological treatments and lifestyle modifications, are reviewed. In conclusion, understanding the concept of neuro-vulnerability in energy metabolism regulation is crucial for addressing metabolic disorders. This review provides valuable insights into the underlying neurobiological mechanisms and their implications for metabolic health. Targeting neuro-vulnerability holds promise for developing innovative strategies in the prevention and treatment of metabolic disorders, ultimately improving metabolic health outcomes.

Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review.

The Western diet is a modern dietary pattern characterized by high intakes of pre-packaged foods, refined grains, red meat, processed meat, high-sugar drinks, candy, sweets, fried foods, conventionally raised animal products, high-fat dairy products, and high-fructose products. The present review aims to describe the effect of the Western pattern diet on the metabolism, inflammation, and antioxidant status; the impact on gut microbiota and mitochondrial fitness; the effect of on cardiovascular health, mental health, and cancer; and the sanitary cost of the Western diet. To achieve this goal, a consensus critical review was conducted using primary sources, such as scientific articles, and secondary sources, including bibliographic indexes, databases, and web pages. Scopus, Embase, Science Direct, Sports Discuss, ResearchGate, and the Web of Science were used to complete the assignment. MeSH-compliant keywords such "Western diet", "inflammation", "metabolic health", "metabolic fitness", "heart disease", "cancer", "oxidative stress", "mental health", and "metabolism" were used. The following exclusion criteria were applied: (i) studies with inappropriate or irrelevant topics, not germane to the review's primary focus; (ii) Ph.D. dissertations, proceedings of conferences, and unpublished studies. This information will allow for a better comprehension of this nutritional behavior and its effect on an individual's metabolism and health, as well as the impact on national sanitary systems. Finally, practical applications derived from this information are made.

The Impact of Anorexia Nervosa and the Basis for Non-Pharmacological Interventions.

Anorexia nervosa is a psychiatric disorder with an unknown etiology that is characterized by an individual's preoccupation with their weight and body structure while denying the severity of their low body weight. Due to the fact that anorexia nervosa is multifaceted and may indicate the coexistence of genetic, social, hormonal, and psychiatric disorders, a description of non-pharmacological interventions can be used to ameliorate or reduce the symptoms of this condition. Consequently, the purpose of the present narrative review is to describe the profile's context in the anorexic person as well as the support they would require from their family and environment. In addition, it is aimed at examining preventative and non-pharmacological interventions, such as nutritional interventions, physical activity interventions, psychological interventions, psychosocial interventions, and physical therapy interventions. To reach the narrative review aims, a critical review was conducted utilizing both primary sources, such as scientific publications, and secondary sources, such as bibliographic indexes, web pages, and databases. Nutritional interventions include nutritional education and an individualized treatment for each patient, physical activity interventions include allowing patients to perform controlled physical activity, psychological interventions include family therapy and evaluation of the existence of other psychological disorders, psychosocial interventions include management of the relationship between the patient and social media and physical therapy interventions include relaxation massages and exercises to relieve pain. All these non-pharmacological interventions need to be individualized based on each patient's needs.

Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.

There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.