Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?

BACKGROUND: We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar. CONCLUSIONS: In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.

Dutch cardio-oncology cohort: Incident cardiovascular disease predisposes to a higher cancer mortality rate.

BACKGROUND: Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. Given their high prevalence, it is important to understand the disease burden of cancer mortality in CVD patients. OBJECTIVE: We aimed to evaluate whether patients with incident CVD have a higher risk of malignancy-related mortality, compared to the general population without CVD. METHODS: We performed a national population-based cohort study selecting patients with incident CVD in the Netherlands between 01 April 2000 and 31 December 2005. A reference cohort was selected from the Dutch population using age, sex and ethnicity. Mortality follow-up data were evaluated after data linkage of national registries from Statistics Netherlands until 31 December 2020. RESULTS: A total of 2,240,879 individuals were selected with a mean follow-up of 12 years (range 0.4-21.0), of which 738,666 patients with incident CVD with a mean age of 71 ± 15 years. Malignancy mortality per 1000 person years was 84 for the reference group and 118 for patients with CVD, with the highest rate of 258 in patients with heart failure. Patients with CVD had a higher malignancy mortality risk, compared to the reference group: HR 1.35 (95%CI 1.33-1.36). Highest risks were observed in patients with venous diseases (HR 2.27, 95%CI 2.17-2.36) and peripheral artery disease (HR 1.87, 95%CI 1.84-2.01). CONCLUSION: Results show that CVD predisposes to a higher cancer mortality rate. Of all CVD subtypes, HF patients have the highest cancer mortality rate and the hazards were highest in patients with venous diseases and peripheral artery disease.

Sex Differences in Mortality Risk after the First Hospitalisation with Lower Extremity Peripheral Arterial Disease.

OBJECTIVE: Lower extremity peripheral arterial disease (PAD) is a severe condition that increases the risk of major adverse cardiovascular events, major adverse limb events, and all cause mortality. This study aimed to investigate the mortality risk among females and males hospitalised for the first time with lower extremity PAD. METHODS: Three cohorts of patients who were admitted for the first time with lower extremity PAD in 2007 - 2010, 2011 - 2014, and 2015 - 2018 were constructed. For the 2007 - 2010 and 2011 - 2014 cohorts, the 28 day, one year, and five year mortality rates were calculated, assessing survival time from date of hospital admission until date of death, end of study period, or censoring. For the 2015 - 2018 cohort, only 28 day and one year mortality were investigated due to lack of follow up data. Mortality rates of these cohorts were compared with the general population using standardised mortality rates (SMRs), and the risk of death between sexes was evaluated using Cox proportional hazards models. Cox models were adjusted for age, cardiovascular disease, and diabetes mellitus to account for potential confounding factors. RESULTS: In total, 7 950, 9 670, and 13 522 patients were included in the 2007 - 2010, 2011 - 2014, and 2015 - 2018 cohorts, respectively. Over 60% of individuals in each cohort were males. Mortality rates at 28 day and one year remained stable across all cohorts, while the five year mortality rate increased for both males and females in the 2011 - 2014 cohort. The SMRs both of females and males with PAD were significantly higher than in the general population. Multivariable regression analyses found no significant differences in mortality risk between sexes at 28 day and one year. However, the five year mortality risk was lower in females, with a hazard ratio of 0.89 (95% confidence interval [CI] 0.83 - 0.97) in the 2007 - 2010 cohort and 0.88 (95% CI 0.82 - 0.94) in the 2011 - 2014 cohort. CONCLUSION: The five year mortality risk has increased, and females face a lower mortality risk than males. Lower extremity PAD still carries unfavourable long term consequences compared with the general population.

The neighourhood obesogenic built environment characteristics (OBCT) index: Practice versus theory.

BACKGROUND: Obesity is a key risk factor for major chronic diseases such as type 2 diabetes and cardiovascular diseases. To extensively characterise the obesogenic built environment, we recently developed a novel Obesogenic Built environment CharacterisTics (OBCT) index, consisting of 17 components that capture both food and physical activity (PA) environments. OBJECTIVES: We aimed to assess the association between the OBCT index and body mass index (BMI) in a nationwide health monitor. Furthermore, we explored possible ways to improve the index using unsupervised and supervised methods. METHODS: The OBCT index was constructed for 12,821 Dutch administrative neighbourhoods and linked to residential addresses of eligible adult participants in the 2016 Public Health Monitor. We split the data randomly into a training (two-thirds; n = 255,187) and a testing subset (one-third; n = 127,428). In the training set, we used non-parametric restricted cubic regression spline to assess index's association with BMI, adjusted for individual demographic characteristics. Effect modification by age, sex, socioeconomic status (SES) and urbanicity was examined. As improvement, we (1) adjusted the food environment for address density, (2) added housing price to the index and (3) adopted three weighting strategies, two methods were supervised by BMI (variable selection and random forest) in the training set. We compared these methods in the testing set by examining their model fit with BMI as outcome. RESULTS: The OBCT index had a significant non-linear association with BMI in a fully-adjusted model (p<0.05), which was modified by age, sex, SES and urbanicity. However, variance in BMI explained by the index was low (<0.05%). Supervised methods increased this explained variance more than non-supervised methods, though overall improvements were limited as highest explained variance remained <0.5%. DISCUSSION: The index, despite its potential to highlight disparity in obesogenic environments, had limited association with BMI. Complex improvements are not necessarily beneficial, and the components should be re-operationalised.

The association of obesogenic environments with weight status, blood pressure, and blood lipids: A cross-sectional pooled analysis across five cohorts.

In this observational cross-sectional study, we investigated the relationship between combined obesogenic neighbourhood characteristics and various cardiovascular disease risk factors in adults, including BMI, systolic blood pressure, and blood lipids, as well as the prevalence of overweight/obesity, hypertension, and dyslipidaemia. We conducted a large-scale pooled analysis, comprising data from five Dutch cohort studies (n = 183,871). Neighbourhood obesogenicity was defined according to the Obesogenic Built-environmental CharacterisTics (OBCT) index. The index was calculated for 1000m circular buffers around participants' home addresses. For each cohort, the association between the OBCT index and prevalence of overweight/obesity, hypertension and dyslipidaemia was analysed using robust Poisson regression models. Associations with continuous measures of BMI, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, and triglycerides were analysed using linear regression. All models were adjusted for age, sex, education level and area-level socio-economic status. Cohort-specific estimates were pooled using random-effects meta-analyses. The pooled results show that a 10 point higher OBCT index score was significantly associated with a 0.17 higher BMI (95%CI: 0.10 to 0.24), a 0.01 higher LDL-cholesterol (95% CI: 0.01 to 0.02), a 0.01 lower HDL cholesterol (95% CI: -0.02 to -0.01), and non-significantly associated with a 0.36 mmHg higher systolic blood pressure (95%CI: -0.14 to 0.65). A 10 point higher OBCT index score was also associated with a higher prevalence of overweight/obesity (PR = 1.03; 95% CI: 1.02 to 1.05), obesity (PR = 1.04; 95% CI: 1.01 to 1.08) and hypertension (PR = 1.02; 95% CI: 1.00 to 1.04), but not with dyslipidaemia. This large-scale pooled analysis of five Dutch cohort studies shows that higher neighbourhood obesogenicity, as measured by the OBCT index, was associated with higher BMI, higher prevalence of overweight/obesity, obesity, and hypertension. These findings highlight the importance of considering the obesogenic environment as a potential determinant of cardiovascular health.

Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.

REVIEW PURPOSE: This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice. FINDINGS: 34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.

Development of an objectively measured walkability index for the Netherlands.

BACKGROUND: Walkability indices have been developed and linked to behavioural and health outcomes elsewhere in the world, but not comprehensively for Europe. We aimed to 1) develop a theory-based and evidence-informed Dutch walkability index, 2) examine its cross-sectional associations with total and purpose-specific walking behaviours of adults across socioeconomic (SES) and urbanisation strata, 3) explore which walkability components drive these associations. METHODS: Components of the index included: population density, retail and service density, land use mix, street connectivity, green space, sidewalk density and public transport density. Each of the seven components was calculated for three Euclidean buffers: 150 m, 500 m and 1000 m around every 6-digit postal code location and for every administrative neighbourhood in GIS. Componential z-scores were averaged, and final indices normalized between 0 and 100. Data on self-reported demographic characteristics and walking behaviours of 16,055 adult respondents (aged 18-65) were extracted from the Dutch National Travel Survey 2017. Using Tobit regression modelling adjusted for individual- and household-level confounders, we assessed the associations between walkability and minutes walking in total, for non-discretionary and discretionary purposes. By assessing the attenuation in associations between partial indices and walking outcomes, we identified which of the seven components drive these associations. We also tested for effect modification by urbanization degree, SES, age and sex. RESULTS: In fully adjusted models, a 10% increase in walkability was associated with a maximum increase of 8.5 min of total walking per day (95%CI: 7.1-9.9). This association was consistent across buffer sizes and purposes of walking. Public transport density was driving the index's association with walking outcomes. Stratified results showed that associations with minutes of non-discretionary walking were stronger in rural compared to very urban areas, in neighbourhoods with low SES compared to high SES, and in middle-aged (36-49 years) compared to young (18-35 years old) and older adults (50-65 years old). CONCLUSIONS: The walkability index was cross-sectionally associated with Dutch adult's walking behaviours, indicating its validity for further use in research.

A comparison of associations with childhood lung function between air pollution exposure assessment methods with and without accounting for time-activity patterns.

BACKGROUND: To investigate associations between annual average air pollution exposures and health, most epidemiological studies rely on estimated residential exposures because information on actual time-activity patterns can only be collected for small populations and short periods of time due to costs and logistic constraints. In the current study, we aim to compare exposure assessment methodologies that use data on time-activity patterns of children with residence-based exposure assessment. We compare estimated exposures and associations with lung function for residential exposures and exposures accounting for time activity patterns. METHODS: We compared four annual average air pollution exposure assessment methodologies; two rely on residential exposures only, the other two incorporate estimated time activity patterns. The time-activity patterns were based on assumptions about the activity space and make use of available external data sources for the duration of each activity. Mapping of multiple air pollutants (NO2, NOX, PM2.5, PM2.5absorbance, PM10) at a fine resolution as input to exposure assessment was based on land use regression modelling. First, we assessed the correlations between the exposures from the four exposure methods. Second, we compared estimates of the cross-sectional associations between air pollution exposures and lung function at age 8 within the PIAMA birth cohort study for the four exposure assessment methodologies. RESULTS: The exposures derived from the four exposure assessment methodologies were highly correlated (R > 0.95) for all air pollutants. Similar statistically significant decreases in lung function were found for all four methods. For example, for NO2 the decrease in FEV1 was -1.40% (CI; -2.54, -0.24%) per IQR (9.14 µg/m3) for front door exposure, and -1.50% (CI; -2.68, -0.30%) for the methodology which incorporates time activity pattern and actual school addresses. CONCLUSIONS: Exposure estimates from methods based on the residential location only and methods including time activity patterns were highly correlated and associated with similar decreases in lung function. Our study illustrates that the annual average exposure to air pollution for 8-year-old children in the Netherlands is sufficiently captured by residential exposures.

Residential exposure to fast-food restaurants and its association with diet quality, overweight and obesity in the Netherlands: a cross-sectional analysis in the EPIC-NL cohort.

BACKGROUND: Unhealthy food environments may contribute to unhealthy diets and risk of overweight and obesity through increased consumption of fast-food. Therefore, we aimed to study the association of relative exposure to fast-food restaurants (FFR) with overall diet quality and risk of overweight and obesity in a sample of older adults. METHODS: We analyzed cross-sectional data of the EPIC-NL cohort (n = 8,231). Data on relative FFR exposure was obtained through linkage of home address in 2015 with a retail outlet database. We calculated relative exposure to FFR by dividing the densities of FFR in street-network buffers of 400, 1000, and 1500 m around the home of residence by the density of all food retailers in the corresponding buffer. We calculated scores on the Dutch Healthy Diet 2015 (DHD15) index using data from a validated food-frequency questionnaire. BMI was categorized into normal weight (BMI < 25), overweight (25 ≤ BMI < 30), and obesity (BMI ≥ 30). We used multivariable linear regression (DHD15-index) and multinomial logistic regression (weight status), using quartiles of relative FFR exposure as independent variable, adjusting for lifestyle and environmental characteristics. RESULTS: Relative FFR exposure was not significantly associated with DHD15-index scores in the 400, 1000, and 1500 m buffers (ßQ4vsQ1= -0.21 [95 %CI: -1.12; 0.70]; ßQ4vsQ1= -0.12 [95 %CI: -1.10; 0.87]; ßQ4vsQ1 = 0.37 [95 %CI: -0.67; 1.42], respectively). Relative FFR exposure was also not related to overweight in consecutive buffers (ORQ4vsQ1=1.10 [95 %CI: 0.97; 1.25]; ORQ4vsQ1=0.97 [95 %CI: 0.84; 1.11]; ORQ4vsQ1= 1.04 [95 %CI: 0.90-1.20]); estimates for obesity were similar to those of overweight. CONCLUSIONS: A high proportion of FFR around the home of residence was not associated with diet quality or overweight and obesity in this large Dutch cohort of older adults. We conclude that although the food environment may be a determinant of food choice, this may not directly translate into effects on diet quality and weight status. Methodological improvements are warranted to provide more conclusive evidence.

Associations between the built environment and obesity: an umbrella review.

BACKGROUND: In the past two decades, the built environment emerged as a conceptually important determinant of obesity. As a result, an abundance of studies aiming to link environmental characteristics to weight-related outcomes have been published, and multiple reviews have attempted to summarise these studies under different scopes and domains. We set out to summarise the accumulated evidence across domains by conducting a review of systematic reviews on associations between any aspect of the built environment and overweight or obesity. METHODS: Seven databases were searched for eligible publications from the year 2000 onwards. We included systematic literature reviews, meta-analyses and pooled analyses of observational studies in the form of cross-sectional, case-control, longitudinal cohort, ecological, descriptive, intervention studies and natural experiments. We assessed risk of bias and summarised results structured by built environmental themes such as food environment, physical activity environment, urban-rural disparity, socioeconomic status and air pollution. RESULTS: From 1850 initial hits, 32 systematic reviews were included, most of which reported equivocal evidence for associations. For food- and physical activity environments, associations were generally very small or absent, although some characteristics within these domains were consistently associated with weight status such as fast-food exposure, urbanisation, land use mix and urban sprawl. Risks of bias were predominantly high. CONCLUSIONS: Thus far, while most studies have not been able to confirm the assumed influence of built environments on weight, there is evidence for some obesogenic environmental characteristics. Registration: This umbrella review was registered on PROSPERO under ID CRD42019135857.

Does the neighbourhood food environment contribute to ethnic differences in diet quality? Results from the HELIUS study in Amsterdam, the Netherlands.

OBJECTIVE: The aim of the current study was to establish whether the neighbourhood food environment, characterised by the healthiness of food outlets, the diversity of food outlets and fast-food outlet density within a 500 m or 1000 m street network buffer around the home address, contributed to ethnic differences in diet quality. DESIGN: Cross-sectional cohort study. SETTING: Amsterdam, the Netherlands. PARTICIPANTS: Data on adult participants of Dutch, South-Asian Surinamese, African Surinamese, Turkish and Moroccan descent (n total 4728) in the HELIUS study were analysed. RESULTS: The neighbourhood food environment of ethnic minority groups living in Amsterdam is less supportive of a healthy diet and of less diversity than that of participants of Dutch origin. For example, participants of Turkish, Moroccan and South-Asian Surinamese descent reside in a neighbourhood with a significantly higher fast-food outlet density (≤1000 m) than participants of Dutch descent. However, we found no evidence that neighbourhood food environment characteristics directly contributed to ethnic differences in diet quality. CONCLUSION: Although ethnic minority groups lived in less healthy food environments than participants of ethnic Dutch origin, this did not contribute to ethnic differences in diet quality. Future research should investigate other direct or indirect consequences of residing in less supportive food environments and gain a better understanding of how different ethnic groups make use of their neighbourhood food environment.

Risk factors of mortality in older patients with dementia in psychiatric care.

OBJECTIVE: To examine the mortality risk, and its risk factors, of older patients with dementia in psychiatric care. METHODS: We constructed a cohort of dementia patients through data linkage of four Dutch registers: the Psychiatric Case Register Middle Netherlands (PCR-MN), the hospital discharge register, the population register, and the national cause of death register. All dementia patients in PCR-MN aged between 60 and 100 years between 1 January 2000 and 31 December 2010 were included. Risk factors of mortality were investigated using Cox proportional hazard regression models with adjustment for age, sex, setting of care, nationality, marital status, dementia type, and psychiatric and somatic comorbidities. RESULTS: In total, 4297 patients were included with a median age of 80 years. The 1-year, 3-year, and 5-year mortality were 16.4%, 44.4%, and 63.5%, respectively. Determinants that increased the 1-year mortality were: male sex (adjusted hazard ratio [HR]: 1.49; 95% confidence interval [95% CI], 1.26-1.76), higher age (HR 1.08; 95% CI, 1.07-1.09), inpatient psychiatric care (HR 1.52; 95% CI, 1.19-1.93), more somatic comorbidities (HR 1.67; 95% CI, 1.49-1.87), and cardiovascular disease separately (HR 1.54; 95% CI, 1.30-1.82). Results for 3-year and 5-year mortality were comparable. Living together/married increased the 3- and 5-year mortality, and Dutch nationality increased the 5-year mortality. There were no differences in mortality with different types of psychiatric comorbidity. CONCLUSION: Mortality of dementia patients in psychiatric care was high, much higher than mortality in the general older population. The results of this study should raise awareness about their unfavourable prognosis, particularly older patients, men, inpatients, and patients with more somatic comorbidity.

A prediction model for one- and three-year mortality in dementia: results from a nationwide hospital-based cohort of 50,993 patients in the Netherlands.

OBJECTIVE: to develop a model to predict one- and three-year mortality in patients with dementia attending a hospital, through hospital admission or day/memory clinic. DESIGN: we constructed a cohort of dementia patients through data linkage of three Dutch national registers: the hospital discharge register (HDR), the population register and the national cause of death register. SUBJECTS: patients with dementia in the HDR aged between 60 and 100 years registered between 1 January 2000 and 31 December 2010. METHODS: logistic regression analysis techniques were used to predict one- and three-year mortality after a first hospitalisation with dementia. The performance was assessed using the c-statistic and the Hosmer-Lemeshow test. Internal validation was performed using bootstrap resampling. RESULTS: 50,993 patients were included in the cohort. Two models were constructed, which included age, sex, setting of care (hospitalised versus day clinic) and the presence of comorbidity using the Charlson comorbidity index. One model predicted one-year mortality and the other three-year mortality. Model discrimination according to the c-statistic for the models was 0.71 (95% CI 0.71-0.72) and 0.72 (95% CI 0.72-0.73), respectively. CONCLUSION: both models display acceptable ability to predict mortality. An important advantage is that they are easy to apply in daily practise and thus are helpful for individual decision-making regarding diagnostic/therapeutic interventions and advance care planning.

Deep phenotyping meets big data: the Geoscience and hEalth Cohort COnsortium (GECCO) data to enable exposome studies in The Netherlands.

Environmental exposures are increasingly investigated as possible drivers of health behaviours and disease outcomes. So-called exposome studies that aim to identify and better understand the effects of exposures on behaviours and disease risk across the life course require high-quality environmental exposure data. The Netherlands has a great variety of environmental data available, including high spatial and often temporal resolution information on urban infrastructure, physico-chemical exposures, presence and availability of community services, and others. Until recently, these environmental data were scattered and measured at varying spatial scales, impeding linkage to individual-level (cohort) data as they were not operationalised as personal exposures, that is, the exposure to a certain environmental characteristic specific for a person. Within the Geoscience and hEalth Cohort COnsortium (GECCO) and with support of the Global Geo Health Data Center (GGHDC), a platform has been set up in The Netherlands where environmental variables are centralised, operationalised as personal exposures, and used to enrich 23 cohort studies and provided to researchers upon request. We here present and detail a series of personal exposure data sets that are available within GECCO to date, covering personal exposures of all residents of The Netherlands (currently about 17 M) over the full land surface of the country, and discuss challenges and opportunities for its use now and in the near future.

Increased mortality and hospital readmission risk in patients with dementia and a history of cardiovascular disease: Results from a nationwide registry linkage study.

OBJECTIVE: To evaluate the impact of cardiovascular disease (CVD) on mortality and readmission risk in patients with dementia. METHODS: Prospective hospital-based cohort of 59 194 patients with dementia admitted to hospital or visiting a day-clinic between 2000 and 2010. Patients were divided in those with and without a history of CVD (ie, previous admission for CVD; coronary heart disease, heart failure, stroke, atrial fibrillation, or other CVD). Absolute mortality risks (ARs), median survival times, and hazard ratios (adjusted for age, sex, and comorbidity) were calculated. RESULTS: Three-year ARs and HRs were higher, and survival times were shorter among patients visiting a day-clinic with a history of CVD than in those without. The differences were less pronounced for inpatients. Readmission risk was further increased in the presence of CVD in both day clinic and inpatients. CONCLUSION: Clinicians need to be more aware of worse prognosis of the population with CVD and dementia.

Relations between air pollution and vascular development in 5-year old children: a cross-sectional study in the Netherlands.

BACKGROUND: Air pollution has been shown to promote cardiovascular disease in adults. Possible mechanisms include air pollution induced changes in arterial wall function and structure. Atherosclerotic vascular disease is a lifelong process and childhood exposure may play a critical role. We investigated whether air pollution is related to arterial wall changes in 5-year old children. To this aim, we developed an air pollution exposure methodology including time-weighted activity patterns improving upon epidemiological studies which assess exposure only at residential addresses. METHODS: The study is part of an existing cohort study in which measurements of carotid artery intima-media thickness, carotid artery distensibility, elastic modulus, diastolic and systolic blood pressure have been obtained. Air pollution assessments were based on annual average concentration maps of Particulate Matter and Nitrogen Oxides at 5 m resolution derived from the European Study of Cohorts for Air Pollution Effects. We defined children's likely primary activities and for each activity we calculated the mean air pollution exposure within the assumed area visited by the child. The exposure was then weighted by the time spent performing each activity to retrieve personal air pollution exposure for each child. Time spent in these activities was based upon a Dutch mobility survey. To assess the relation between the vascular status and air pollution exposure we applied linear regressions in order to adjust for potential confounders. RESULTS: Carotid artery distensibility was consistently associated with the exposures among the 733 5-years olds. Regression analysis showed that for air pollution exposures carotid artery distensibility decreased per standard deviation. Specifically, for NO2, carotid artery distensibility decreased by - 1.53 mPa- 1 (95% CI: -2.84, - 0.21), for NOx by - 1.35 mPa- 1 (95% CI: -2.67, - 0.04), for PM2.5 by - 1.38 mPa- 1 (95% CI: -2.73, - 0.02), for PM10 by - 1.56 mPa- 1 (95% CI: -2.73, - 0.39), and for PM2.5absorbance by - 1.63 (95% CI: -2.30, - 0.18). No associations were observed for the rest outcomes. CONCLUSIONS: The results of this study support the view that air pollution exposure may reduce arterial distensibility starting in young children. If the reduced distensibility persists, this may have clinical relevance later in life. The results of this study further stress the importance of reducing environmental pollutant exposures.

Sex differences in mortality after heat waves: are elderly women at higher risk?

BACKGROUND AND OBJECTIVE: Climate change leads to more frequent, intense and longer-lasting heat waves which can have severe health outcomes. The elderly are a high-risk population for heat-related mortality and some studies suggested that elderly women are more affected by extreme heat than men. This study aimed to review the presence of sex-specific results in studies performed on mortality in elderly (> 65 years old) after heat waves in Europe. METHODS: A literature search was conducted in July 2017 on papers published in databases Pubmed and Web of Science between January 2000 and December 2016. RESULTS: 68 papers that included mortality data for elderly after heat waves were identified. The 13 of them which presented results distinguished by sex and age group were included in the review. Eight studies showed worse health outcome for elderly women compared to men. One study showed higher mortality rates for men, two found no sex differences and two studies presented inconsistent results. CONCLUSION: Studies that present sex-stratified data on mortality after heat waves seem to indicate that elderly women are at higher risk than men. Future research is warranted to validate this finding. Furthermore, a better understanding on the underlying physiological or social mechanisms for possible sex and gender differences in excessive deaths for this vulnerable population is needed to set up appropriate policy measures.

Association of Stroke Among Adults Aged 18 to 49 Years With Long-term Mortality.

Importance: Stroke remains the second leading cause of death worldwide. Approximately 10% to 15% of all strokes occur in young adults. Information on prognosis and mortality specifically in young adults is limited. Objective: To determine short- and long-term mortality risk after stroke in young adults, according to age, sex, and stroke subtype; time trends in mortality; and causes of death. Design, Setting, and Participants: Registry- and population-based study in the Netherlands of 15 527 patients aged 18 to 49 years with first stroke between 1998 and 2010, and follow-up until January 1, 2017. Patients and outcomes were identified through linkage of the national Hospital Discharge Registry, national Cause of Death Registry, and the Dutch Population Register. Exposures: First stroke occurring at age 18 to 49 years, documented using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes for ischemic stroke, intracerebral hemorrhage, and stroke not otherwise specified. Main Outcomes and Measures: Primary outcome was all-cause cumulative mortality in 30-day survivors at end of follow-up, stratified by age, sex, and stroke subtype, and compared with all-cause cumulative mortality in the general population. Results: The study population included 15 527 patients with stroke (median age, 44 years [interquartile range, 38-47 years]; 53.3% women). At end of follow-up, a total of 3540 cumulative deaths had occurred, including 1776 deaths within 30 days after stroke and 1764 deaths (23.2%) during a median duration of follow-up of 9.3 years (interquartile range, 5.9-13.1 years). The 15-year mortality in 30-day survivors was 17.0% (95% CI, 16.2%-17.9%). The standardized mortality rate compared with the general population was 5.1 (95% CI, 4.7-5.4) for ischemic stroke (observed mortality rate 12.0/1000 person-years [95% CI, 11.2-12.9/1000 person-years]; expected rate, 2.4/1000 person-years; excess rate, 9.6/1000 person-years) and the standardized mortality rate for intracerebral hemorrhage was 8.4 (95% CI, 7.4-9.3; observed rate, 18.7/1000 person-years [95% CI, 16.7-21.0/1000 person-years]; expected rate, 2.2/1000 person-years; excess rate, 16.4/1000 person-years). Conclusions and Relevance: Among young adults aged 18 to 49 years in the Netherlands who were 30-day survivors of first stroke, mortality risk compared with the general population remained elevated up to 15 years later.

Cardiovascular Disease Prevention Policy in Human Immunodeficiency Virus: Recommendations From a Modeling Study.

Background: Cardiovascular disease (CVD) is expected to contribute a large noncommunicable disease burden among human immunodeficiency virus (HIV)-infected people. We quantify the impact of prevention interventions on annual CVD burden and costs among HIV-infected people in the Netherlands. Methods: We constructed an individual-based model of CVD in HIV-infected people using national ATHENA (AIDS Therapy Evaluation in The Netherlands) cohort data on 8791 patients on combination antiretroviral therapy (cART). The model follows patients as they age, develop CVD (by incorporating a CVD risk equation), and start cardiovascular medication. Four prevention interventions were evaluated: (1) increasing the rate of earlier HIV diagnosis and treatment; (2) avoiding use of cART with increased CVD risk; (3) smoking cessation; and (4) intensified monitoring and drug treatment of hypertension and dyslipidemia, quantifying annual number of averted CVDs and costs. Results: The model predicts that annual CVD incidence and costs will increase by 55% and 36% between 2015 and 2030. Traditional prevention interventions (ie, smoking cessation and intensified monitoring and treatment of hypertension and dyslipidemia) will avert the largest number of annual CVD cases (13.1% and 20.0%) compared with HIV-related interventions-that is, earlier HIV diagnosis and treatment and avoiding cART with increased CVD risk (0.8% and 3.7%, respectively)-as well as reduce cumulative CVD-related costs. Targeting high-risk patients could avert the majority of events and costs. Conclusions: Traditional CVD prevention interventions can maximize cardiovascular health and defray future costs, particularly if targeting high-risk patients. Quantifying additional public health benefits, beyond CVD, is likely to provide further evidence for policy development.

Decline in mortality in patients with dementia: Results from a nationwide cohort of 44 258 patients in the Netherlands during 2000 to 2008.

OBJECTIVE: To investigate whether mortality and readmission risk have changed over the last decade. METHODS: Prospective hospital-based cohort of 44 258 patients with dementia admitted to hospital or visiting a day clinic between 2000 and 2008. Absolute risks (ARs) of 1- and 3-year mortality and 1-year hospital readmission were quantified and stratified by type of care (day clinic or inpatient care). Cox models were used to compare hazard ratios (HRs), adjusted for age, sex, comorbidity, of death, and readmission across the years using 2000 as the reference group. RESULTS: One-year mortality declined among men visiting a day clinic (AR in 2008 versus 2000: 13.0%, 29.9%; HR 0.41, 95% CI, 0.30-0.55). Among inpatients, these ARs were 48.7%, 53.0% (HR 0.85, 95% CI, 0.77-0.94). Three-year mortality also declined (AR for men visiting a day clinic: 37.5%, 58.4%, HR 0.53, 95% CI, 0.43-0.64; for inpatients: 74.4%, 78.9%, HR 0.80, 95% CI, 0.73-0.88). Whereas 1-year readmission risk decreased among men visiting a day clinic (AR 44.1%, 65.9%, HR 0.52, 95% CI, 0.43-0.63), the risk increased among inpatients (AR 36.9%, 27.6%, HR 1.48, 95% CI, 1.28-1.72). CONCLUSION: One- and 3-year mortality remarkably declined. One-year hospital readmission risk increased among inpatients and decreased among patients visiting a day clinic. The results should raise awareness for the increased survival with dementia, as this has direct consequences for patients and (in)formal caregivers, and probably also for health care costs.