Stella Trompet

Leiden University Medical Centre | LUMC · Department of Cardiology & Department of Gerontology and Geriatrics

The 1-HMR metabolomics-based MetaboHealth score, comprised of 14 serum metabolic markers, associates with disease-specific mortality, but it is unclear whether the score also reflects cognitive changes and functional impairment. We aimed to assess the associations between the MetaboHealth score with cognitive function and functional decline in olde...

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and...

Introduction The prevalence of depressive symptoms and cognitive decline increases with age, reducing quality of life. However, the temporal relationship between the two remains elusive. Objectives We aimed to explore the temporal relationship between depressive symptoms and cognitive decline in individuals aged 85 years, during up to 5 years foll...

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer’s disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 indi...

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patie...

Purpose The aim of the present study was to investigate characteristics and outcomes in vaccinated and unvaccinated older patients hospitalized for COVID-19 infection. Methods A retrospective multicentre cohort study among patients aged ≥70 years hospitalized for COVID-19 infection. Results 263 vaccinated and 82 unvaccinated patients were include...

Purpose Viral mutations and improved prevention or treatment options may have changed the association of frailty with mortality throughout the COVID-19 pandemic. We investigated how associations of frailty with in-hospital mortality changed throughout the pandemic in older people hospitalised for COVID-19. Methods The COVID-OLD study included COVI...

Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. This study aims to investigate the association between clinical frailty and immune-related tr...

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread...

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals ( P < 5 × 10 ⁻⁸ ) from the largest single-stage blood pressure (BP) genome-wide association study to date ( n = 1,028,980 European individuals). These associations explain more than 60% of single nucle...

INTRODUCTION The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS We combined data from...

OBJECTIVE To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association wi...

Purpose: The aim of the present study was to investigate characteristics and outcomes in vaccinated and unvaccinated older patients hospitalized for COVID-19 infection. Methods: A retrospective multicentre cohort study among patients aged ≥70 years hospitalized for COVID-19 infection. Results: 263 vaccinated and 82 unvaccinated patients were includ...

Introduction: To tailor treatment for older patients with cancer, an oncogeriatric care pathway has been developed in the Leiden University Medical Center. In this care pathway a geriatric assessment is performed and preferences concerning cancer treatment options are discussed. This study aimed to explore patient experiences with and attitudes tow...

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1–7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8–11. Here we present a...

Background Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, r...

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% n...

Coagulation Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with cir...

Aims To investigate the differences between Indonesian urban and rural populations in the association of lifestyle and clinical factors with diabetes prevalence. Methods Using database of the 2018 Indonesian Basic Health Survey, which was conducted in April-May 2018, non-pregnant respondents aged ≥15 years old with available blood glucose data (n...

Introduction: Esophageal cancer is the seventh most common cancer worldwide and typically tends to manifest at an older age. Marked heterogeneity in time-dependent functional decline in older adults results in varying grades of clinically manifest patient fitness or frailty. The biological age-related adaptations that accompany functional decline...

Background: The 1-HMR metabolomics-based MetaboHealth score, comprised of 14 serum metabolic markers, associates with disease-specific mortality, but it is unclear whether the score also reflects cognitive changes and functional impairment. Objectives: Assess the associations between the MetaboHealth score with cognitive and daily functioning, and...

Background & aims Clinical guidelines often recommend to treat individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment on...

Background Randomized trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalizability of results to individuals with low vitamin D status is unclear. We characterized dose—response relationships between 25-hydroxyvitamin D [25(OH)D] concentrations and risk of co...

Background The broad concept of health as “the ability to adapt and self‐manage in the face of social, physical and emotional challenges” has been operationalized by “Positive Health,” a framework increasingly used in the Netherlands. We explored to what degree the impact of the COVID‐19 pandemic and preventive measures on Positive Health differed...

Importance Although older patients are at increased risk of developing grade 3 or higher chemotherapy-related toxic effects, no studies, to our knowledge, have focused on the association between toxic effects and quality of life (QOL) and physical functioning. Objective To investigate the association between grade 3 or higher chemotherapy-related...

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of...

BACKGROUND Type 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular compli...

Introduction: Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older patients with solid tumors. The aim of this systematic review was to evaluate the evidence on the association of blood biomarkers with treatment response and adverse health...

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and...

Background Older individuals are often underrepresented in clinical trials. In 2012 only 7% of RCT’s specifically studied older people and their geriatric characteristics were poorly reported. The aim of this review was to investigate temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012...

Background: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and hi...

Background and aims: Mendelian randomization confirmed multiple risk factors for primary events of coronary artery disease (CAD), but no such studies have been performed on recurrent major coronary events despite interesting insights derived from other designs. We examined the associations between genetically-influenced classical cardiovascular ri...

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,2...

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and...

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and wome...

Introduction: Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatme...

Background and aims: Leptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation bet...

Tandem CAG repeat sizes of 36 or more in the huntingtin gene (HTT) cause Huntington disease. Apart from neuropsychiatric complications, the disease is also accompanied by metabolic dysregulation and weight loss, which contribute to a progressive functional decline. Recent studies also reported an association between repeats below the pathogenic thr...

Health care expenditure in the last year of life makes up a high proportion of medical spending across the world. This is often framed as waste, but this framing is only meaningful if it is known at the time of treatment who will go on to die. We analyze the distribution of health care spending by predicted mortality for the Danish population over...

Objective to investigate the association between variability and loss of body weight with subsequent cognitive performance and activities of daily living in older individuals. Design cross-sectional cohort study. Setting PROspective Study of Pravastatin in the Elderly at Risk, multicentre trial with participants from Scotland, Ireland and the Net...

Biological age-related adaptations have been shown to modulate the non-malignant cells comprising the tumor microenvironment (TME). In the current work, we studied the association between biological age and TME characteristics in patients with esophageal adenocarcinoma. We comparatively assessed intratumoral histologic stroma quantity, tumor immune...

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism 1–7 . This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases 8–11 . Here we presen...

Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic,...

Objective: Few prospective studies have assessed whether persons with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. We conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroi...

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1,...

Background Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in la...

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in t...

Background Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genet...

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci atta...

In this study, we aimed to investigate differences in lifestyle factors and prevalence of metabolic syndrome (MetS) in the Indonesian population between 2013 and 2018. In addition, we investigated whether adherence to the 2015-released national healthy lifestyle guideline (‘GERMAS’) is associated with MetS in different sex, age, urban/rural, and BM...

Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism...

Background as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. Objective to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. Methods this was a multicentre retrospecti...

Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independ...

Background: Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes a...

Background In non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates ma...