Towards Better Culturally Tailored Cardiometabolic Prevention Among the South-Asian Surinamese in the Netherlands

Objectives: To gain insight in the motives and determinants for the uptake of healthy lifestyles by South-Asian Surinamese people to identify needs and engagement strategies for healthy lifestyle support.Methods: We used a mixed-method design: first, focus groups with South-Asian Surinamese women; second, a questionnaire directed at their social network, and third, interviews with health professionals. Qualitative content analysis, basic statistical analyses and triangulation of data were applied.Results: Sixty people participated (n = 30 women, n = 20 social network, n = 10 professionals). Respondent groups reported similar motives and determinants for healthy lifestyles. In general, cardiometabolic prevention was in line with the perspectives and needs of South-Asian Surinamese. However, there seems to be a mismatch too: South-Asian Surinamese people missed a culturally sensitive approach, whereas professionals experienced difficulty with patient adherence. Incremental changes to current lifestyles; including the social network, and an encouraging approach seem to be key points for improvement of professional cardiometabolic prevention.Conclusion: Some key points for better culturally tailoring of preventive interventions would meet the needs and preferences of the South-Asian Surinamese living in the Netherlands

Psychosocial factors and cancer incidence (PSY-CA):Protocol for individual participant data meta-analyses

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer.METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2).CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.</p

Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.

BACKGROUND: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. RESULTS: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. CONCLUSIONS: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.BH

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies

A registry-based algorithm to predict ejection fraction in patients with heart failure

Aims Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes. Methods and results We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF &amp;gt;= vs. &amp;lt;50% and (ii) EF &amp;gt;= vs. &amp;lt;40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF &amp;gt;= 50% and 0.76 (95% CI 0.75-0.76) for EF &amp;gt;= 40%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort. Conclusions Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.Funding Agencies|Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Servier, the NetherlandsNetherlands Government; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart [116074]; Swedish Research CouncilSwedish Research Council [2013-23897-104604-23, 523-2014-2336]; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation [20150557, 20170841]; Stockholm County CouncilStockholm County Council [20140220, 20170112]; UCL Hospitals NIHR Biomedical Research Centre; Dutch Heart Foundation, a part of Facts and Figures</p

Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction

Aims We aimed to derive and validate clinically useful clusters of patients with heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction &amp;gt;= 50%). Methods and results We derived a cluster model from 6909 HFpEF patients from the Swedish Heart Failure Registry (SwedeHF) and externally validated this in 2153 patients from the Chronic Heart Failure ESC-guideline based Cardiology practice Quality project (CHECK-HF) registry. In SwedeHF, the median age was 80 [interquartile range 72-86] years, 52% of patients were female and most frequent comorbidities were hypertension (82%), atrial fibrillation (68%), and ischaemic heart disease (48%). Latent class analysis identified five distinct clusters: cluster 1 (10% of patients) were young patients with a low comorbidity burden and the highest proportion of implantable devices; cluster 2 (30%) patients had atrial fibrillation, hypertension without diabetes; cluster 3 (25%) patients were the oldest with many cardiovascular comorbidities and hypertension; cluster 4 (15%) patients had obesity, diabetes and hypertension; and cluster 5 (20%) patients were older with ischaemic heart disease, hypertension and renal failure and were most frequently prescribed diuretics. The clusters were reproduced in the CHECK-HF cohort. Patients in cluster 1 had the best prognosis, while patients in clusters 3 and 5 had the worst age- and sex-adjusted prognosis. Conclusions Five distinct clusters of HFpEF patients were identified that differed in clinical characteristics, heart failure drug therapy and prognosis. These results confirm the heterogeneity of HFpEF and form a basis for tailoring trial design to individualized drug therapy in HFpEF patients.Funding Agencies|Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Servier, the NetherlandsNetherlands Government; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2013-23897-104604-23, 523-2014-2336]; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation [20150557, 20170841]; Stockholm County CouncilStockholm County Council [20140220, 20170112]; UCL Hospitals NIHR Biomedical Research Centre; Dutch Heart Foundation, as part of Facts and Figures</p

Risk of coronary artery disease in adults with congenital heart disease : A comparison with the general population

BACKGROUND: Coronary artery disease (CAD) will increasingly determine outcome in the aging adult congenital heart disease (CHD) population. We aimed to determine sex-specific incidence of CAD in adult CHD patients throughout adulthood, compared to the general population. METHODS AND RESULTS: We followed 11,723 adult CHD patients (median age 33 years; 49% male; 57% mild, 34% moderate, 9% severe CHD) from the Dutch CONCOR registry, and two age-sex-matched persons per patient from the general population for first CAD event in national registers (period 2002-2012). Incidence rates were estimated using smoothed hazard functions. CAD risk during follow-up, stratified by CHD severity, was compared using proportional subdistribution hazards regression. In ACHD patients, 103 CAD events (43 women) occurred over 60,456 person-years. Rates per 1000person-years increased from 0.3(95% confidence interval: 0.1-0.6) at age 20 to 5.8(3.7-8.9) at 70 years in female, and from 0.5(0.3-1.0) to 7.8(5.1-11.8) in male patients. Compared to the general population, relative risk was 12.0(2.5-56.3) in women and 4.6(1.7-12.1) in men aged 20 years. Relative risk declined with age, remaining significant up to age ~65 years in women and ~50 years in men. In patients with mild, moderate and severe CHD, CAD risk was 1.3(0.9-1.9), 1.6(1.0-2.5) and 2.9(1.3-6.9) times increased compared to the general population, respectively. CONCLUSIONS: We found increased CAD risk in adult CHD patients, with greater relative risk at younger age, in women and those with more severe CHD. These results underline the importance of screening for and treatment of CAD risk factors in these patients

Risk of coronary artery disease in adults with congenital heart disease: A comparison with the general population

Background: Coronary artery disease (CAD) will increasingly determine outcome in the aging adult congenital heart disease (CHD) population. We aimed to determine sex-specific incidence of CAD in adult CHD patients throughout adulthood, compared to the general population. Methods and results: We followed 11,723 adult CHD patients (median age 33 years; 49% male; 57% mild, 34% moderate, 9% severe CHD) from the Dutch CONCOR registry, and two age-sex-matched persons per patient from the general population for first CAD event in national registers (period 2002–2012). Incidence rates were estimated using smoothed hazard functions. CAD risk during follow-up, stratified by CHD severity, was compared using proportional subdistribution hazards regression. In ACHD patients, 103 CAD events (43 women) occurred over 60,456 person-years. Rates per 1000person-years increased from 0.3(95% confidence interval: 0.1–0.6) at age 20 to 5.8(3.7–8.9) at 70 years in female, and from 0.5(0.3–1.0) to 7.8(5.1–11.8) in male patients. Compared to the general population, relative risk was 12.0(2.5–56.3) in women and 4.6(1.7–12.1) in men aged 20 years. Relative risk declined with age, remaining significant up to age ~65 years in women and ~50 years in men. In patients with mild, moderate and severe CHD, CAD risk was 1.3(0.9–1.9), 1.6(1.0–2.5) and 2.9(1.3–6.9) times increased compared to the general population, respectively. Conclusions: We found increased CAD risk in adult CHD patients, with greater relative risk at younger age, in women and those with more severe CHD. These results underline the importance of screening for and treatment of CAD risk factors in these patients

Generalizability of randomized controlled trials in heart failure with reduced ejection fraction

BACKGROUND: Heart failure (HF) trials have stringent inclusion and exclusion criteria, but limited data exist regarding generalizability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries. METHODS AND RESULTS: Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients. CONCLUSION: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries