Explore the vast range of titles available.

Objectives Further survival benefits may be gained from low-dose chest computed tomography (CT) by assessing vertebral fractures and bone density. We sought to assess the association between CT-measured vertebral fractures and bone density with all-cause mortality in lung cancer screening participants. Methods Following a case-cohort design, lung cancer screening trial participants ( N  = 3,673) who died ( N  = 196) during a median follow-up of 6 years (inter-quartile range: 5.7–6.3) were identified and added to a random sample of N  = 383 from the trial. We assessed vertebral fractures using Genant´s semiquantative method on sagittal reconstructions and measured bone density (Hounsfield Units (HU)) in vertebrae. Cox proportional hazards modelling was used to determine if vertebral fractures or bone density were independently predictive of mortality. Results The prevalence of vertebral fractures was 35 % (95 % confidence interval 30–40 %) among survivors and 51 % (44–58 %) amongst cases. After adjusting for age, gender, smoking status, pack years smoked, coronary and aortic calcium volume and pulmonary emphysema, the adjusted hazard ratio (HR) for vertebral fracture was 2.04 (1.43–2.92). For each 10 HU decline in trabecular bone density, the adjusted HR was 1.08 (1.02–1.15). Conclusions Vertebral fractures and bone density are independently associated with all-cause mortality. Key Points • Lung cancer screening chest computed tomography contains additional, potentially useful information. • Vertebral fractures and bone density are independently predictive of mortality. • This finding has implications for screening and management decisions.

Background Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. Methods Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. Results 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2–11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01–1.46 and HR 1.26, 95% CI 1.10–1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. Conclusion Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

Previous reports on the incidence of schizophrenia in immigrant groups to The Netherlands were based on hospital data. To compare the incidence of psychotic disorders in the immigrant groups to that in natives. Two-year first-contact incidence study in The Hague. The risks of schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV criteria) were increased for subjects born in Morocco (gender and age-adjusted relative risk=4.5; 95% Cl 1.4-8.5), Surinam (relative risk=3.2; 1.8-5.7), The Netherlands Antilles (relative risk=2.9; 0.9-9.5) and other non-Western countries (relative risk=2.4; 1.3-4.7). This risk was also increased for Moroccans (relative risk=8.0; 2.6-24.5) and Surinamese (relative risk=5.5; 2.5-11.9) of the second generation. The risks for Turkish immigrants, first or second generation, and for immigrants from Western countries were not significantly increased. This study indicates that the incidence of schizophrenia is increased in several, but not all, immigrant groups to The Netherlands. It is possible that factors associated with a process of rapid westernisation precipitate schizophrenia in people who are genetically at risk.

Objective To investigate whether an internet based, nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinically manifest vascular disease.Design Prospective randomised controlled trial.Setting Multicentre trial in secondary and tertiary healthcare setting.Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with at least two treatable risk factors not at goal.Intervention Personalised website with an overview and actual status of patients’ risk factors and mail communication via the website with a nurse practitioner for 12 months; the intervention combined self management support, monitoring of disease control, and drug treatment.Main outcome measures The primary endpoint was the relative change in Framingham heart risk score after 1 year. Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor.Results Participants’ mean age was 59.9 (SD 8.4) years, and most patients (n=246; 75%) were male. After 1 year, the relative change in Framingham heart risk score of the intervention group compared with the usual care group was −14% (95% confidence interval −25% to −2%). At baseline, the Framingham heart risk score was higher in the intervention group than in the usual care group (16.1 (SD 10.6) v 14.0 (10.5)), so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score. This produced a relative change of −12% (−22% to −3%) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and −8% (−18% to 2%) adjusted for the baseline score. Of the individual risk factors, a difference between groups was observed in low density lipoprotein cholesterol (−0.3, −0.5 to −0.1, mmol/L) and smoking (−7.7%, −14.9% to −0.4%). Some other risk factors tended to improve (body mass index, triglycerides, systolic blood pressure, renal function) or tended to worsen (glucose concentration, albuminuria).Conclusion An internet based, nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease.Trial registration Clinical trials NCT00785031.

Background: Abdominal adiposity is associated with various risk factors including hypertension, and is therefore particularly relevant in patients with stable cerebrovascular disease (CeVD). A U-shaped relation between body mass index (BMI, kg m − 2 ) and cardiovascular events is often described. Whether this U-shape persists for abdominal adiposity, and consequently which reference values should guide clinical practice, is unclear. We described the relation between multiple adiposity measurements and risk of vascular events, vascular mortality, malignancy and all-cause mortality in patients with clinically stable CeVD. Methods: During a median follow-up time of 6.8 years, 1767 patients were prospectively followed. Relations were assessed using multivariable adjusted Cox proportional hazards models. Adiposity was assessed with BMI, waist circumference (stratified by gender) and the contribution of visceral fat to total abdominal fat (VAT%) measured using ultrasound. Relations were nonlinear if the χ 2 -statistic of the nonlinear term was significant ( P -value<0.05). Nadirs were reported for nonlinear and hazard ratios (HRs) for linear relations. Results: The relations between BMI and outcomes were nonlinear with nadirs ranging between 27.1 (95% confidence interval (CI) 21.9–29.3) kg m 2 for vascular mortality and 28.1 (95% CI, 19.0–38.2)) kg m − 2 for malignancy. The relation between waist circumference and all-cause mortality was nonlinear with a nadir of 84.0 (95% CI, 18.7–134.8) cm for females and 94.8 (95% CI, 80.3–100.1) cm for males. No nonlinearity was detected for VAT%. A 1-s.d. (9.8%) increase in VAT% was related to both vascular (HR, 1.23, 95% CI 1.00–1.51) and all-cause mortality (HR, 1.22, 95% CI 1.05–1.42). Conclusions: In patients with CeVD, a BMI around 27–28 kg m − 2 relates to the lowest risk of vascular events, vascular mortality, malignancy and all-cause mortality. However, increasing abdominal adiposity confers a higher risk of all-cause mortality. Thus, whereas traditional BMI cutoffs may be re-evaluated in this population, striving for low abdominal obesity should remain a goal.

Background: Apolipoprotein E ( APOE ) genotypes are associated with different plasma lipid levels. People with the APO ɛ2 genotype can develop a disorder called dysbetalipoproteinemia (DBL). A possible predisposing factor for DBL is adiposity. We evaluated whether and to what extent the APOE genotype modifies the relation between adiposity and lipids in patients with manifest arterial disease and we looked at possible determinants of DBL in ɛ2 homo- and heterozygote patients. Methods: This prospective cohort study was performed in 5450 patients with manifest arterial disease from the Secondary Manifestations of ARTerial disease (SMART) study. The APOE genotype was measured in all patients and revealed 58 ɛ2 homozygotes, 663 ɛ2 heterozygotes, 3181 ɛ3 homozygotes and 1548 ɛ4 carriers. The main dependent variable was non-high-density lipoprotein cholesterol (non-HDL-c). The relation between adiposity (including body mass index (BMI), waist circumference (waist), visceral adipose tissue (VAT) and metabolic syndrome (MetS)) and lipids was evaluated with linear regression analyses. Determinants of DBL were evaluated using logistic regression. Results: There was significant effect modification by the APOE genotype on the relation between non-HDL-c and BMI, waist, VAT and MetS. There was an association between BMI and non-HDL-c in ɛ2 homozygotes ( β 0.173, 95% confidence interval (CI) 0.031–0.314, P =0.018) and ɛ4 carriers ( β 0.033, 95% CI 0.020–0.046, P <0.001). In all genotypes, there was an effect of waist, VAT and MetS on non-HDL-c, but these effects were most distinct in ɛ2 homozygotes (waist β 0.063, 95% CI 0.015–0.110, P =0.011; VAT β 0.580, 95% CI 0.270–0.889, P =0.001; MetS β 1.760, 95% CI 0.668–2.852, P =0.002). Determinants of DBL in ɛ2 homo- and heterozygotes were VAT and MetS. Conclusion: The APOE genotype modifies the relation between adiposity and plasma lipid levels in patients with vascular disease. The relation between adiposity and lipids is present in all patients, but it is most distinct in ɛ2 homozygote patients. Abdominal fat and MetS are determinants of DBL.

To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical setting. The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ˗ diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naïve approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics. C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82–0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74–0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age). Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing.

The 'vascular depression' hypothesis states that brain changes located in frontal-subcortical pathways increase vulnerability for specific depressive symptom profiles, but studies examining locations of small-vessel and degenerative changes with individual symptoms are scarce. We examined whether location and progression of white-matter lesions (WMLs), lacunar infarcts and atrophy were associated with motivational and mood symptoms in patients with symptomatic atherosclerotic disease. In 578 patients [63 (s.d.=8) years] of the Second Manifestations of ARTerial disease (SMART)-Medea study, volumes of WMLs and atrophy and visually rated infarcts were obtained with 1.5 T magnetic resonance imaging at baseline and after 3.9 (s.d.=0.4) years' follow-up. Depressive symptoms were assessed with Patient Health Questionnaire-9 at follow-up and categorized into motivational and mood symptoms. Regression analyses adjusted for age, gender, education, Mini-Mental State Examination, physical functioning, antidepressant use and vascular risk factors showed that location in mainly deep white-matter tracts and progression of WMLs were associated with symptoms of anhedonia, concentration problems, psychomotor retardation and appetite disturbance. Lacunar infarcts in deep white matter were associated with greater motivational [Incidence rate ratio (IRR) 1.7, 95% confidence interval (CI) 1.2-2.4] and mood (IRR 1.7, 95% CI 1.1-2.6) sumscores, and with symptoms of psychomotor retardation, energy loss and depressed mood; lacunar infarcts in the thalamus were associated with psychomotor retardation only. Cortical atrophy was associated with symptoms of anhedonia and appetite disturbance. Excluding patients with major depression did not materially change the results. Our findings suggest that disruption of frontal-subcortical pathways by small-vessel lesions leads to a symptom profile that is mainly characteristic of motivational problems, also in the absence of major depression.

Background: In patients with carotid artery stenosis, ipsilateral hemodynamic compromise is associated with an increased risk of stroke. It is unclear which factors determine cerebral perfusion. We studied the effect of both the degree of the stenosis and the collateral circulation via the circle of Willis (CoW) on cerebral perfusion in patients with symptomatic carotid artery stenosis. Methods: In 88 patients with unilateral symptomatic carotid artery stenosis of ≧50%, CT perfusion was used to measure the relative cerebral blood volume (rCBV), the difference in mean transit time (ΔMTT) and the relative cerebral blood flow (rCBF). CT angiography was used to measure the degree of carotid stenosis and to assess the configuration of the CoW. Differences in mean rCBF, rCBV and ΔMTT between patients with a carotid stenosis of ≤69, 70–79, 80–89 and 90–99%, and between patients with a complete and those with an incomplete CoW were determined by analysis of covariance. Results: The ipsilateral rCBF showed a gradual decrease with increasing severity of carotid stenosis (1.09 ± 0.06, 0.93 ± 0.06, 0.90 ± 0.04 and 0.83 ± 0.04 ml/100 g/min, respectively; p = 0.005), and the ΔMTT showed a gradual increase (–0.02 ± 0.33, 0.16 ± 0.34, 1.08 ± 0.22 and 1.47 ± 0.20 s, respectively; p < 0.001). The rCBV was not related to the severity of stenosis. No relation was found between the configuration of the CoW and the cerebral perfusion parameters. Conclusions: Cerebral perfusion is inversely related to the degree of stenosis in patients with symptomatic carotid artery stenosis. A relation between the configuration of the CoW and cerebral perfusion was not detected, suggesting that other collateral pathways play an important role.

Aims: Adiposity is associated with an increased but also with a decreased risk for successive vascular events or mortality in patients with different manifestations of vascular disease. In this study we directly compare the risk of general adiposity or abdominal obesity on the occurrence of new vascular events or mortality in these patients. Methods: Patients with cerebrovascular disease (CVD; n =973), coronary artery disease (CAD; n =2339) or peripheral arterial disease (PAD; n =894) were prospectively followed for the occurrence of a vascular event or death. The median follow-up was 4.5 years. Adiposity was assessed with body mass index (BMI), waist circumference (WC) and determination of intra-abdominal fat through ultrasound. Cox proportional hazards models were used to evaluate the risk for new vascular events, vascular mortality and all-cause mortality. Results: CAD patients had a 12% increased risk for vascular mortality with 1 BMI unit increase (hazard ratio (HR) 1.12; 95% confidence interval (CI) 1.05–1.20) and a 25% increased risk with 1cm increase in intra-abdominal adipose tissue (HR 1.25; 95% CI 1.12–1.39). The risk for all-cause mortality was increased by 3% (HR 1.03; 95% CI 1.01–1.05) with 1 cm increase in WC and was increased by 15% (HR 1.15; 95% CI 1.06–1.25) with 1 cm increase in intra-abdominal adipose tissue. In PAD patients there was an inverse relationship between BMI and vascular mortality (HR 0.93; 95% CI 0.87–0.98) and all-cause mortality (HR 0.90; 95% CI 0.86–0.94). In CVD patients there was no relation between obesity and vascular events or mortality. Conclusion: General adiposity is associated with an increased risk for vascular mortality in CAD patients and a decreased risk for (vascular) mortality in PAD patients.