Effect of a Digitally-Enabled, Preventive Health Program on Blood Pressure in an Adult, Dutch General Population Cohort:An Observational Pilot Study

Worldwide, it is estimated that at least one in four adults suffers from hypertension, and this number is expected to increase as populations grow and age. Blood pressure (BP) possesses substantial heritability, but is also heavily modulated by lifestyle factors. As such, digital, lifestyle-based interventions are a promising alternative to standard care for hypertension prevention and management. In this study, we assessed the prevalence of elevated and high BP in a Dutch general population cohort undergoing a health screening, and observed the effects of a subsequent self-initiated, digitally-enabled lifestyle program on BP regulation. Baseline data were available for 348 participants, of which 56 had partaken in a BP-focused lifestyle program and got remeasured 10 months after the intervention. Participants with elevated SBP and DBP at baseline showed a mean decrease of 7.2 mmHg and 5.4 mmHg, respectively. Additionally, 70% and 72.5% of participants showed an improvement in systolic and diastolic BP at remeasurement. These improvements in BP are superior to those seen in other recent studies. The long-term sustainability and the efficacy of this and similar digital lifestyle interventions will need to be established in additional, larger studies

A Pilot Study on the Prevalence of Micronutrient Imbalances in a Dutch General Population Cohort and the Effects of a Digital Lifestyle Program

Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study, we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults and evaluated the effect of a digital lifestyle program on the nutritional status and nutrition health behaviors of these individuals. A micronutrient panel was measured in 348 participants, alongside a dietary assessment. One hundred users subsequently underwent a remeasurement. We identified at least one nutritional imbalance in 301 individuals (86.5%). A total of 80% improved and normalized B6, 67% improved folate, 70% improved B12, and 86% improved vitamin D. Iron abnormalities were corrected in 75% of the participants. In conclusion, this study found that micronutrient deficiencies of easily obtainable vitamins through diet or supplementation such as B vitamins and vitamin D were more prevalent than expected in a Dutch population. This can partly be explained by insufficient consumption of food groups rich in B vitamins. Our preliminary results in those remeasured after a digitally enabled lifestyle intervention show these imbalances can be corrected with adequate behavioral support complemented with supplementation where needed

Development and validation of decision rules models to stratify coronary artery disease, diabetes, and hypertension risk in preventive care:Cohort study of returning UK biobank participants

Many predictive models exist that predict risk of common cardiometabolic conditions. However, a vast majority of these models do not include genetic risk scores and do not distinguish between clinical risk requiring medical or pharmacological interventions and pre-clinical risk, where lifestyle interventions could be first-choice therapy. In this study, we developed, validated, and compared the performance of three decision rule algorithms including biomarkers, physical measurements, and genetic risk scores for incident coronary artery disease (CAD), diabetes (T2D), and hypertension against commonly used clinical risk scores in 60,782 UK Biobank participants. The rules models were tested for an association with incident CAD, T2D, and hypertension, and hazard ratios (with 95% confidence interval) were calculated from survival models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), and Net Reclassification Index (NRI). The higher risk group in the decision rules model had a 40-, 40.9-, and 21.6-fold increased risk of CAD, T2D, and hypertension, respectively (p < 0.001 for all). Risk increased significantly between the three strata for all three conditions (p < 0.05). Based on genetic risk alone, we identified not only a high-risk group, but also a group at elevated risk for all health conditions. These decision rule models comprising blood biomarkers, physical measurements, and polygenic risk scores moderately improve commonly used clinical risk scores at identifying individuals likely to benefit from lifestyle intervention for three of the most common lifestyle-related chronic health conditions. Their utility as part of digital data or digital therapeutics platforms to support the implementation of lifestyle interventions in preventive and primary care should be further validated

Developing Effective Questionnaire-Based Prediction Models for Type 2 Diabetes for Several Ethnicities

Background: Type 2 diabetes disproportionately affects individuals of non-white ethnicity through a complex interaction of multiple factors. Early disease prediction and detection is therefore essential and requires tools that can be deployed at large scale. We aimed to tackle this problem by developing questionnaire-based prediction models for type 2 diabetes for multiple ethnicities.Methods: Logistic regression models, using questionnaire-only features, were trained on the White population of the UK Biobank, and validated in five other ethnicities and externally in Lifelines. In total, 631,748 individuals were included for prevalence prediction and 67,083 individuals for the eight-year incidence prediction. Predictive accuracy was assessed and a detailed sensitivity analysis was conducted to assess potential clinical utility. Furthermore, we compared the questionnaire algorithms to clinical non-laboratory type 2 diabetes risk tools.Findings: Our algorithms accurately predicted type 2 diabetes prevalence (AUC=0·901) and eight-year incidence (AUC=0·873) in the White UK Biobank population. Both models replicate well in Lifelines, with AUCs of 0·917 and 0·817 for prevalence and incidence. Both models performed consistently well across ethnicities, with AUCs of 0·855 to 0·894 for prevalence and from 0·819 to 0·883 for incidence. These models generally outperformed two clinically validated non-laboratory tools and correctly reclassified &gt;3,000 type 2 diabetes cases. Model performance improved with the addition of blood biomarkers, but not with the addition of physical measurements.Interpretation: Easy-to-implement, questionnaire-based models can predict prevalent and incident type 2 diabetes with high accuracy across all ethnicities, providing a highly-scalable solution for population-wide risk stratification

Changes in Blood Lipid Levels After a Digitally Enabled Cardiometabolic Preventive Health Program: Pre-Post Study in an Adult Dutch General Population Cohort

Background: Despite widespread education, many individuals fail to follow basic health behaviors such as consuming a healthy diet and exercising. Positive changes in lifestyle habits are associated with improvements in multiple cardiometabolic health risk factors, including lipid levels. Digital lifestyle interventions have been suggested as a viable complement or potential alternative to conventional health behavior change strategies. However, the benefit of digital preventive interventions for lipid levels in a preventive health context remains unclear. Objective: This observational study aimed to determine how the levels of lipids, namely total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and triglycerides, changed over time in a Dutch general population cohort undergoing a digital preventive health program. Moreover, we looked to establish associations between lifestyle factors at baseline and lipid levels. Methods: We included 348 adults from the Dutch general population who underwent a digitally enabled preventive health program at Ancora Health between January 2020 and October 2021. Upon enrollment, participants underwent a baseline assessment involving a comprehensive lifestyle questionnaire, a blood biochemistry panel, physical measurements, and cardiopulmonary fitness measurements. Thereafter, users underwent a lifestyle coaching program and could access the digital application to register and track health behaviors, weight, and anthropometric data at any time. Lipid levels were categorized as normal, elevated, high, and clinical dyslipidemia according to accepted international standards. If at least one lipid marker was high or HDL was low, participants received specific coaching and advice for cardiometabolic health. We retrospectively analyzed the mean and percentage changes in lipid markers in users who were remeasured after a cardiometabolic health-focused intervention, and studied the association between baseline user lifestyle characteristics and having normal lipid levels. Results: In our cohort, 199 (57.2%) participants had dyslipidemia at baseline, of which 104 participants were advised to follow a cardiometabolic health-focused intervention. Eating more amounts of favorable food groups and being more active were associated with normal lipid profiles. Among the participants who underwent remeasurement 9 months after intervention completion, 57% (17/30), 61% (19/31), 56% (15/27), 82% (9/11), and 100% (8/8) showed improvements at remeasurement for total, LDL, HDL, and non-HDL cholesterol, and triglycerides, respectively. Moreover, between 35.3% and 77.8% showed a return to normal levels. In those with high lipid levels at baseline, total cholesterol decreased by 0.5 mmol/L (7.5%), LDL cholesterol decreased by 0.39 mmol/L (10.0%), non-HDL cholesterol decreased by 0.44 mmol/L (8.3%), triglycerides decreased by 0.97 mmol/L (32.0%), and HDL increased by 0.17 mmol/L (15.6%), after the intervention. Conclusions: A cardiometabolic screening program in a general population cohort identified a significant portion of individuals with subclinical and clinical lipid levels. Individuals who, after screening, actively engaged in a cardiometabolic health-focused lifestyle program improved their lipid levels

The necessity of incorporating non-genetic risk factors into polygenic risk score models

The growing public interest in genetic risk scores for various health conditions can be harnessed to inspire preventive health action. However, current commercially available genetic risk scores can be deceiving as they do not consider other, easily attainable risk factors, such as sex, BMI, age, smoking habits, parental disease status and physical activity. Recent scientific literature shows that adding these factors can improve PGS based predictions significantly. However, implementation of existing PGS based models that also consider these factors requires reference data based on a specific genotyping chip, which is not always available. In this paper, we offer a method naïve to the genotyping chip used. We train these models using the UK Biobank data and test these externally in the Lifelines cohort. We show improved performance at identifying the 10% most at-risk individuals for type 2 diabetes (T2D) and coronary artery disease (CAD) by including common risk factors. Incidence in the highest risk group increases from 3.0- and 4.0-fold to 5.8 for T2D, when comparing the genetics-based model, common risk factor-based model and combined model, respectively. Similarly, we observe an increase from 2.4- and 3.0-fold to 4.7-fold risk for CAD. As such, we conclude that it is paramount that these additional variables are considered when reporting risk, unlike current practice with current available genetic tests

Adipogenic and SWAT cells separate from a common progenitor in human brown and white adipose depots

Adipocyte function is a major determinant of metabolic disease, warranting investigations of regulating mechanisms. We show at single-cell resolution that progenitor cells from four human brown and white adipose depots separate into two main cell fates, an adipogenic and a structural branch, developing from a common progenitor. The adipogenic gene signature contains mitochondrial activity genes, and associates with genome-wide association study traits for fat distribution. Based on an extracellular matrix and developmental gene signature, we name the structural branch of cells structural Wnt-regulated adipose tissue-resident (SWAT) cells. When stripped from adipogenic cells, SWAT cells display a multipotent phenotype by reverting towards progenitor state or differentiating into new adipogenic cells, dependent on media. Label transfer algorithms recapitulate the cell types in human adipose tissue datasets. In conclusion, we provide a differentiation map of human adipocytes and define the multipotent SWAT cell, providing a new perspective on adipose tissue regulation.ISSN:2522-581

Improving the diagnostic yield of exome-sequencing by predicting gene-phenotype associations using large-scale gene expression analysis

The diagnostic yield of exome and genome sequencing remains low (8-70%), due to incomplete knowledge on the genes that cause disease. To improve this, we use RNA-seq data from 31,499 samples to predict which genes cause specific disease phenotypes, and develop GeneNetwork Assisted Diagnostic Optimization (GADO). We show that this unbiased method, which does not rely upon specific knowledge on individual genes, is effective in both identifying previously unknown disease gene associations, and flagging genes that have previously been incorrectly implicated in disease. GADO can be run on www.genenetwork.nl by supplying HPO-terms and a list of genes that contain candidate variants. Finally, applying GADO to a cohort of 61 patients for whom exome-sequencing analysis had not resulted in a genetic diagnosis, yields likely causative genes for ten cases