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A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features.

ABSTRACT: Cardiovascular diseases are a public health concern; they remain the leading cause of morbidity and mortality in patients with type 2 diabetes. Phenotypic information available from retinal fundus images and clinical measurements, in addition to genomic data, can identify relevant biomarkers of cardiovascular health. In this study, we assessed whether such biomarkers stratified risks of major adverse cardiac events (MACE). A retrospective analysis was carried out on an extract from the Tayside GoDARTS bioresource of participants with type 2 diabetes (n?=?3,891). A total of 519 features were incorporated, summarising morphometric properties of the retinal vasculature, various single nucleotide polymorphisms (SNPs), as well as routine clinical measurements. After imputing missing features, a predictive model was developed on a randomly sampled set (n?=?2,918) using L1-regularised logistic regression (lasso). The model was evaluated on an independent set (n?=?973) and its performance associated with overall hazard rate after censoring (log-rank p?

SUBMITTER: Fetit AE

PROVIDER: S-EPMC6401035 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features.

Fetit Ahmed E AE Doney Alexander S AS Hogg Stephen S Wang Ruixuan R MacGillivray Tom T Wardlaw Joanna M JM Doubal Fergus N FN McKay Gareth J GJ McKenna Stephen S Trucco Emanuele E

Scientific reports 20190305 1

Cardiovascular diseases are a public health concern; they remain the leading cause of morbidity and mortality in patients with type 2 diabetes. Phenotypic information available from retinal fundus images and clinical measurements, in addition to genomic data, can identify relevant biomarkers of cardiovascular health. In this study, we assessed whether such biomarkers stratified risks of major adverse cardiac events (MACE). A retrospective analysis was carried out on an extract from the Tayside G ...[more]

PMID: 30837638

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Project description:Type 2 diabetes mellitus (T2DM) is continuously rising with more disease cases every year. T2DM is a chronic disease with many severe comorbidities and therefore remains a burden for the patient and the society. Disease prevention, early diagnosis, and stratified treatment are important elements in slowing down the increase in diabetes prevalence. T2DM has a substantial genetic component with an estimated heritability of 40-70%, and more than 500 genetic loci have been associated with T2DM. Because of the intrinsic genetic basis of T2DM, one tool for risk assessment is genome-wide genetic risk scores (GRS). Current GRS only account for a small proportion of the T2DM risk; thus, better methods are warranted for more accurate risk assessment. T2DM is correlated with several other diseases and complex traits, and incorporating this information by adjusting effect size of the included markers could improve risk prediction. The aim of this study was to develop multi-trait (MT)-GRS leveraging correlated information. We used phenotype and genotype information from the UK Biobank, and summary statistics from two independent T2DM studies. Marker effects for T2DM and seven correlated traits, namely, height, body mass index, pulse rate, diastolic and systolic blood pressure, smoking status, and information on current medication use, were estimated (i.e., by logistic and linear regression) within the UK Biobank. These summary statistics, together with the two independent training summary statistics, were incorporated into the MT-GRS prediction in different combinations. The prediction accuracy of the MT-GRS was improved by 12.5% compared to the single-trait GRS. Testing the MT-GRS strategy in two independent T2DM studies resulted in an elevated accuracy by 50-94%. Finally, combining the seven information traits with the two independent T2DM studies further increased the prediction accuracy by 34%. Across comparisons, body mass index and current medication use were the two traits that displayed the largest weights in construction of the MT-GRS. These results explicitly demonstrate the added benefit of leveraging correlated information when constructing genetic scores. In conclusion, constructing GRS not only based on the disease itself but incorporating genomic information from other correlated traits as well is strongly advisable for obtaining improved individual risk stratification.

Project description:ImportanceThe potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts.ObjectiveTo investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population.Design, setting, and participantsThis cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022.Main outcomes and measuresRetinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers.ResultsA total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (-4.05 μm, 95% CI, -5.40 to -2.69; P = 5.4 × 10-9), which persisted when investigating only patients without diabetes (-3.99 μm; 95% CI, -6.67 to -1.30; P = .004) or just those 55 years and younger (-2.90 μm; 95% CI, -5.55 to -0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (-0.14 units; 95% CI, -0.22 to -0.05; P = .001), although this was not present when excluding patients with diabetes.Conclusions and relevanceIn this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.

Project description:BACKGROUND:Diabetes is a significant public health issue. Saudi Arabia has the highest prevalence of type 2 diabetes mellitus (T2DM) in the Arab world. Currently, it affects 31.6% of the general population, and the prevalence of T2DM is predicted to rise to 45.36% by 2030. Mobile health (mHealth) offers improved and cost-effective care to people with T2DM. However, the efficiency of engagement strategies and features of this technology need to be reviewed and standardized according to stakeholder and expert perspectives. OBJECTIVE:The main objective of this study was to identify the most agreed-upon features for T2DM self-management mobile apps; the secondary objective was to identify the most agreed-upon strategies that prompt users to use these apps. METHODS:In this study, a 4-round modified Delphi method was applied by experts in the domain of diabetes care. RESULTS:In total, 11 experts with a mean age of 47.09 years (SD 11.70) consented to participate in the study. Overall, 36 app features were generated. The group of experts displayed weak agreement in their ranking of intervention components (Kendall W=0.275; P<.001). The top 5 features included insulin dose adjustment according to carbohydrate counting and blood glucose readings (5.36), alerting a caregiver of abnormal or critical readings (6.09), nutrition education (12.45), contacts for guidance if required (12.64), and offering patient-specific education tailored to the user's goals, needs, and blood glucose readings (12.90). In total, 21 engagement strategies were generated. Overall, the experts showed a moderate degree of consensus in their strategy rankings (Kendall W=0.454; P<.001). The top 5 engagement strategies included a user-friendly design (educational and age-appropriate design; 2.82), a free app (3.73), allowing the user to communicate or send information/data to a health care provider (HCP; 5.36), HCPs prescribing the mobile app in the clinic and asking about patients' app use compliance during clinical visits (6.91), and flexibility and customization (7.91). CONCLUSIONS:This is the first study in the region consisting of a local panel of experts from the diabetes field gathering together. We used an iterative process to combine the experts' opinions into a group consensus. The results of this study could thus be useful for health app developers and HCPs and inform future decision making on the topic.

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A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features.

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A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features.

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