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Showing papers by "Diederick E. Grobbee published in 2010"


Journal ArticleDOI
TL;DR: Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes, including respiratory, digestive, and skin conditions, and no relationship was found between repeated episodes of severe hypglycemia and vascular outcomes or death.
Abstract: Background Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes. Methods We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes, using Cox proportional-hazards models with adjustment for covariates measured at baseline and after randomization. Results During a median follow-up period of 5 years, 231 patients (2.1%) had at least one severe hypoglycemic episode; 150 had been assigned to intensive glucose control (2.7% of the 5571 patients in that group), and 81 had been assigned to standard glucose control (1.5% of the 5569 patients in that group). The median times from the onset of severe hypoglycemia to the first major macrovascular event, the first major microvascular event, and death were 1.56 years (interquartile range, 0.84 to 2.41), 0.99 years (interquartile range, 0.40 to 2.17), and 1.05 years (interquartile range, 0.34 to 2.41), respectively. During follow-up, severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events (hazard ratio, 2.88; 95% confidence interval [CI], 2.01 to 4.12), major microvascular events (hazard ratio, 1.81; 95% CI, 1.19 to 2.74), death from a cardiovascular cause (hazard ratio, 2.68; 95% CI, 1.72 to 4.19), and death from any cause (hazard ratio, 2.69; 95% CI, 1.97 to 3.67) (P<0.001 for all comparisons). Similar associations were apparent for a range of nonvascular outcomes, including respiratory, digestive, and skin conditions (P<0.01 for all comparisons). No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death. Conclusions Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.)

1,280 citations


Journal ArticleDOI
TL;DR: Endovascular and open repair of abdominal aortic aneurysm resulted in similar rates of survival six years after randomization, and the rate of secondary interventions was significantly higher for endovascular repair.
Abstract: BACKGROUND For patients with large abdominal aortic aneurysms, randomized trials have shown an initial overall survival benefit for elective endovascular repair over conventional open repair. This survival difference, however, was no longer significant in the second year after the procedure. Information regarding the comparative outcome more than 2 years after surgery is important for clinical decision making. METHODS We conducted a long-term, multicenter, randomized, controlled trial comparing open repair with endovascular repair in 351 patients with an abdominal aortic aneurysm of at least 5 cm in diameter who were considered suitable candidates for both techniques. The primary outcomes were rates of death from any cause and reintervention. Survival was calculated with the use of Kaplan-Meier methods on an intention-to-treat basis. RESULTS We randomly assigned 178 patients to undergo open repair and 173 to undergo endovascular repair. Six years after randomization, the cumulative survival rates were 69.9% for open repair and 68.9% for endovascular repair (difference, 1.0 percentage point; 95% confidence interval [CI], -8.8 to 10.8; P=0.97). The cumulative rates of freedom from secondary interventions were 81.9% for open repair and 70.4% for endovascular repair (difference, 11.5 percentage points; 95% CI, 2.0 to 21.0; P=0.03). CONCLUSIONS Six years after randomization, endovascular and open repair of abdominal aortic aneurysm resulted in similar rates of survival. The rate of secondary interventions was significantly higher for endovascular repair. (ClinicalTrials.gov number, NCT00421330.)

904 citations


Journal ArticleDOI
TL;DR: Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events, and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia.

821 citations


Journal ArticleDOI
TL;DR: This study shows that simple methods to deal with missing data can lead to seriously misleading results, and advises to consider multiple imputation.

506 citations


Journal ArticleDOI
TL;DR: Mortality risk, particularly by heart failure, is increased by virtually all complications, particularly in the young, and is equally hazardous in younger as in older patients.
Abstract: Aims Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. Methods and results The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regression was used to assess mortality predictors. Of 6933 patients, 197 (2.8%) died during a follow-up of 24 865 patient-years. Compared with the general national population, there was excess mortality, particularly in the young. Median age at death was 48.8 years. Of all deaths, 77% had a cardiovascular origin; 45% were due to chronic heart failure (26%, age 51.0 years) or sudden death (19%, age 39.1 years). Age predicted mortality, as did gender, severity of defect, number of interventions, and number of complications [hazard ratio (HR) range 1.1–5.9, P < 0.05]. Several complications predicted all-cause mortality beyond the effects of age, gender, and congenital heart disease severity, i.e. endocarditis, supraventricular arrhythmias, ventricular arrhythmias, conduction disturbances, myocardial infarction, and pulmonary hypertension (HR range 1.4–3.1, P < 0.05). These risks were similar in patients above and below 40 years of age. Almost all complications predicted death due to heart failure (HR range 2.0–5.1, P < 0.05); conduction disturbances and pulmonary hypertension predicted sudden death (HR range 2.0–4.7, P < 0.05). Conclusion Mortality is increased in adults with congenital heart disease, particularly in the young. The vast majority die from cardiovascular causes. Mortality risk, particularly by heart failure, is increased by virtually all complications. Complications are equally hazardous in younger as in older patients.

503 citations


Journal ArticleDOI
TL;DR: Diets high in animal protein are associated with an increased diabetes risk and a similar association is suggested for total protein itself instead of only animal sources, indicating that accounting for protein content in dietary recommendations for diabetes prevention may be useful.
Abstract: OBJECTIVE Dietary recommendations are focused mainly on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high-protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association among dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy % from protein at the expense of 5 energy % from either carbohydrates or fat was associated with diabetes risk. RESEARCH DESIGN AND METHODS A prospective cohort study was conducted among 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Dietary protein intake was measured with a validated food frequency questionnaire. Incident diabetes was verified against medical records. RESULTS During 10 years of follow-up, 918 incident cases of diabetes were documented. Diabetes risk increased with higher total protein (hazard ratio 2.15 [95% CI 1.77–2.60] highest vs. lowest quartile) and animal protein (2.18 [1.80–2.63]) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy % from total or animal protein at the expense of 5 energy % from carbohydrates or fat increased diabetes risk. CONCLUSIONS Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This finding indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

291 citations


Journal ArticleDOI
TL;DR: Treatment with beta-blockers may reduce the risk of exacerbations and improve survival in patients with COPD, possibly as a result of dual cardiopulmonary protective properties.
Abstract: tients (30.8%) died and 1055 (47.3%) had at least 1 exacerbationofCOPD.Thecrudeandadjustedhazardratios with Cox regression analysis of -blocker use for mortality were 0.70 (95% confidence interval [CI], 0.590.84) and 0.68 (95% CI, 0.56-0.83), respectively. The crudeandadjustedhazardratiosforexacerbationofCOPD were 0.73 (95% CI, 0.63-0.83) and 0.71 (95% CI, 0.600.83), respectively. The adjusted hazard ratios with the propensity score methods were even lower. Subgroup analyses revealed that patients with COPD but without overt cardiovascular disease had similar results. Conclusion:Treatment with-blockers may reduce the riskofexacerbationsandimprovesurvivalinpatientswith COPD,possiblyasaresultofdualcardiopulmonaryprotective properties. Arch Intern Med. 2010;170(10):880-887

286 citations


Journal ArticleDOI
TL;DR: Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders, and is more pronounced in those with the more altered immune function.
Abstract: Objective: Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. Method: This randomized, double-blind, placebo-controlled study was conducted between May 2004 and August 2007. Seventy antipsychotictreated inpatients and outpatients from 10 psychiatric hospitals in The Netherlands with a DSM-IV–diagnosed schizophrenia spectrum disorder were included. Patients were randomized to adjuvant treatment with aspirin 1000 mg/d or placebo. During a 3-month follow-up, psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Other assessments included cognitive tests and immune function. The primary efficacy outcome was the change in total PANSS score. Secondary outcomes were changes in the PANSS subscales and cognitive test results. Results: Mixed-effect models showed a 4.86-point (95% CI, 0.91 to 8.80) and 1.57-point (95% CI, 0.06 to 3.07) larger decrease in the aspirin group compared to the placebo group on the total and positive PANSS score, respectively. Similar but not statistically significant results were observed for the other PANSS subscale scores. Treatment efficacy on total PANSS score was substantially larger in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded. Conclusion: Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development. Trial Registration: controlled-trials.com

247 citations


Journal ArticleDOI
Solveig Gretarsdottir1, Annette F. Baas2, Gudmar Thorleifsson, Hilma Holm, Martin den Heijer3, Jean-Paul P. M. de Vries, Steef Kranendonk, Clark J. Zeebregts4, Steven M.M. van Sterkenburg, Robert H. Geelkerken, Andre M. van Rij5, Michael J.A. Williams5, A.P.M. Boll, Jelena Kostic, Adalbjorg Jonasdottir, Aslaug Jonasdottir, G. Bragi Walters, Gisli Masson, Patrick Sulem, Jona Saemundsdottir, Magali Mouy, Kristinn P. Magnusson, Gerard Tromp, James R. Elmore, Natzi Sakalihasan6, Raymond Limet6, Jean-Olivier Defraigne6, Robert E. Ferrell7, Antti Ronkainen8, Ynte M. Ruigrok2, Cisca Wijmenga, Diederick E. Grobbee2, Svati H. Shah9, Christopher B. Granger9, Arshed A. Quyyumi10, Viola Vaccarino10, Riyaz S. Patel10, Riyaz S. Patel11, A. Maziar Zafari10, Allan I. Levey10, Harland Austin10, Domenico Girelli12, Pier Franco Pignatti12, Oliviero Olivieri12, Nicola Martinelli12, Giovanni Malerba12, Elisabetta Trabetti12, Lewis C. Becker13, Diane M. Becker13, Muredach P. Reilly14, Daniel J. Rader14, Thomas Mueller, Benjamin Dieplinger, Meinhard Haltmayer, Sigitas Urbonavicius15, Bengt Lindblad, Anders Gottsäter, Eleonora Gaetani16, Roberto Pola16, Roberto Pola17, Philip S. Wells18, Marc A. Rodger18, Melissa A. Forgie19, Nicole Langlois18, Javier Corral20, Vicente Vicente20, Jordi Fontcuberta, Francisco España, Niels Grarup, Torben Jørgensen21, Daniel R. Witte, Torben Hansen22, Oluf Pedersen21, Katja K.H. Aben3, Jacqueline de Graaf3, Suzanne Holewijn3, Lasse Folkersen23, Anders Franco-Cereceda23, Per Eriksson23, David A. Collier24, Hreinn Stefansson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Einar M. Valdimarsson, Hulda B Magnadottir, Sigurlaug Sveinbjörnsdóttir, Isleifur Olafsson, Magnus K. Magnusson25, Robert Palmason, Vilhelmina Haraldsdottir25, Karl Andersen25, Pall T. Onundarson25, Gudmundur Thorgeirsson25, Lambertus A. Kiemeney3, Janet T. Powell26, David J. Carey, Helena Kuivaniemi, Jes S. Lindholt15, Gregory T. Jones5, Augustine Kong, Jan D. Blankensteijn3, Stefan E Matthiasson25, Unnur Thorsteinsdottir25, Kari Stefansson25 
TL;DR: It was found that rs7025486[A], located within DAB2IP, which encodes an inhibitor of cell growth and survival, is associated with early onset myocardial infarction, but not with intracranial aneurysm or ischemic stroke.
Abstract: We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

204 citations


Journal ArticleDOI
TL;DR: The Netherlands has contributed two cohort studies to EPIC and the Julius Center and the RIVM decided to combine efforts to maintain and expand the cohorts and biobanks by merging them into one EPICNetherlands (EPIC-NL) study.
Abstract: A major scientific challenge for the next few decades is to understand the interaction between genetic susceptibility and environmental factors in the aetiology of chronic diseases. The most promising approach to discover these interactions requires a combined effort of epidemiology and molecular genetics and large sample sizes for sufficient power. Already in the early 90s, the European Prospective Investigation Into Cancer and Nutrition (EPIC) was initiated in 10 European countries to create a large cohort to study the aetiology of chronic diseases. The Netherlands has contributed two cohort studies to EPIC: the Prospect cohort of 17 357 women of the Julius Center in Utrecht, and the Monitoring Project on Risk Factors for Chronic Diseases (MORGEN) cohort of 22 654 men and women of the National Institute for Public Health and the Environment (RIVM) in Bilthoven. In the design phase, both cohorts collaborated closely to obtain maximal synergy in the design of the questionnaires and to follow identical protocols in the collection of biological samples. Because of the efficiency gain in maintaining the cohort infrastructure and in conducting scientific analyses, the Julius Center and the RIVM decided to combine efforts to maintain and expand the cohorts and biobanks by merging them into one EPICNetherlands (EPIC-NL) study.

181 citations


Journal ArticleDOI
TL;DR: MIM should not be used in handling missing confounder data because it gives unpredictable bias of the odds ratio even with small percentages of missing values, and CC can be used when missing values are completely random, but it gives loss of statistical power.

Journal ArticleDOI
01 Jun 2010-Heart
TL;DR: Hospital utilisation in registered and medically supervised adult patients with congenital heart disease is high and increases with age, and admission rates are at least two times higher than in the general population, and most marked in the older age groups.
Abstract: Objective To assess the extent and the characteristics of hospital admissions in registered adult patients with congenital heart disease. Design Observational cohort study. Setting The Netherlands. Patients 5798 adult patients with congenital heart disease from the Dutch CONCOR national registry linked to the Dutch National Medical Registration (Prismant). Main outcome measures All hospital admissions from the years 2001 up until 2006. Results During 28990 patient-years, 2908 patients (50%) were admitted to hospital. Median age at admission was 39 years (range 18e86 years); 46% were male. Admission rate in CONCOR patients was high among all ages (range 11e68%) and exceeded that of the general Dutch population two to three times; this difference was most pronounced in the older age groups. Altogether there were 8916 admissions, 5411 (61%) of which were for cardiovascular indications. Among cardiovascular admissions, referrals for arrhythmias were most common (31%). Of 4926 interventions, 2459 (50%) were cardiovascular, most often reparative interventions or cardioversion (53%). Most non-cardiovascular admissions were obstetric. Among defects, univentricular heart and tricuspid atresia had the highest incidence and duration of admission. Conclusions Healthcare utilisation in registered and medically supervised adult patients with congenital heart disease is high and increases with age. Admission rates are at least two times higher than in the general population, and most marked in the older age groups. With the ageing of this population, a major increase in healthcare utilisation is imminent in the near future. Timely preparation of healthcare resources is crucial to sustain optimal care.

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TL;DR: This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes.
Abstract: OBJECTIVE To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We used data from a prospective cohort study in 38,094 Dutch men and women, aged 20–70 years. Dietary phylloquinone and menaquinones intakes were assessed using a validated food frequency questionnaire. Diabetes case patients were ascertained mainly via self-report and verified against medical records. RESULTS During 10.3 years of follow-up, 918 incident cases of diabetes were documented. In a multivariate model adjusting for diabetes risk factors and dietary factors, phylloquinone intake tended to be associated ( P = 0.08) with a reduced risk of type 2 diabetes with a hazard ratio (HR) of 0.81 (95% CI 0.66–0.99) for the highest versus the lowest quartile. For menaquinones intake, a linear, inverse association ( P = 0.038) with risk of type 2 diabetes was observed with an HR of 0.93 (0.87–1.00) for each 10-μg increment in the multivariate model. CONCLUSIONS This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes.

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TL;DR: Diets high in GL, GI, and starch and low in fiber were associated with an increased diabetes risk, and both carbohydrate quantity and quality seem to be important factors in diabetes prevention.

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TL;DR: The results suggest a slight risk reduction for CHD mortality with moderate coffee consumption and strengthen the evidence on the lower risk of CHD with coffee and tea consumption.
Abstract: Objective—To examine the associations of coffee and tea consumption with risk of morbidity and mortality of stroke and coronary heart disease (CHD) and with all-cause mortality. Methods and Results—Coffee and tea consumption were assessed with a validated food-frequency questionnaire, and 37 514 participants were observed for 13 years for the occurrence of cardiovascular morbidity and mortality. A U-shaped association between coffee and CHD was found, with the lowest hazard ratio (HR [95% CI]) for 2.1 to 3.0 cups per day (0.79 [0.65 to 0.96]; Ptrend0.01). Tea was inversely associated with CHD, with the lowest HR (95% CI) for more than 6.0 cups per day (0.64 [0.46 to 0.90]; Ptrend0.02). No associations between tea or coffee and stroke were found (Ptrend0.63 and Ptrend0.32, respectively). Although not significant, coffee slightly reduced the risk for CHD mortality (HR, 0.64; 95% CI, 0.37 to 1.11; Ptrend0.12) for 3.1 to 6.0 cups per day. A U-shaped association between tea and CHD mortality was observed, with an HR of 0.55 (95% CI, 0.31 to 0.97; Ptrend0.03) for 3.1 to 6.0 cups per day. Neither coffee nor tea was associated with stroke (Ptrend0.22 and Ptrend0.74, respectively) and all-cause mortality (Ptrend0.33 and Ptrend0.43, respectively). Conclusion—High tea consumption is associated with a reduced risk of CHD mortality. Our results suggest a slight risk reduction for CHD mortality with moderate coffee consumption and strengthen the evidence on the lower risk of CHD with coffee and tea consumption. (Arterioscler Thromb Vasc Biol. 2010;30:1665-1671.)

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TL;DR: In subjects already at lower risk of type 2 diabetes on the basis of multiple low-risk lifestyle behaviors, moderate alcohol consumption was associated with an approximately 40% lower risk compared with abstention.

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TL;DR: The treatment benefits of a routine administration of a fixed combination of perindopril-indapamide to patients with type 2 diabetes on cardiovascular and renal outcomes, and death, are consistent across all stages of CKD at baseline.
Abstract: Aims Individuals with diabetes and chronic kidney disease (CKD) are at high risk for cardiovascular disease. In these analyses of the ADVANCE trial, we assessed the effects of a fixed combination of perindopril–indapamide on renal and cardiovascular outcomes in patients with type 2 diabetes according to baseline CKD stage. Methods and results Patients with type 2 diabetes were randomized to perindopril–indapamide (4 mg/1.25 mg) or placebo. Treatment effects on cardiovascular (cardiovascular death, myocardial infarction, or stroke) and renal outcomes were compared in subgroups defined by baseline Kidney Disease Outcome Quality Initiative CKD stage. Homogeneity in treatment effect was tested by adding interaction terms to the relevant Cox models. The study included 10 640 participants with known CKD status, of whom 6125 did not have CKD, 2482 were classified as CKD stage 1 or 2, and 2033 as CKD stage ≥3. The relative treatment effects on major cardiovascular events were similar across all stages of CKD, with no heterogeneity in the magnitude of the effects for any outcome. In contrast, the absolute treatment effects approximately doubled in those with CKD stage ≥3 when compared to those with no CKD. For every 1000 patients with CKD stage ≥3 treated for 5 years, active treatment prevented 12 cardiovascular events when compared with six events per 1000 patients with no CKD. Conclusion The treatment benefits of a routine administration of a fixed combination of perindopril–indapamide to patients with type 2 diabetes on cardiovascular and renal outcomes, and death, are consistent across all stages of CKD at baseline. Absolute risk reductions are larger in patients with CKD highlighting the importance of blood pressure-lowering in this population.

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TL;DR: Routine administration of perindopril–indapamide lowers blood pressure safely and reduces the risk of major clinical outcomes in patients of at least 75 years with type 2 diabetes.
Abstract: OBJECTIVE: The efficacy and safety of blood pressure lowering in elderly patients have not been sufficiently investigated in patients with diabetes. Using data from the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation study, we assessed the efficacy and safety of routine blood pressure lowering to prevent major clinical outcomes in elderly patients with type 2 diabetes. METHODS: Eleven thousand one hundred and forty patients aged at least 55 years with type 2 diabetes (mean 66+/-6 years) were randomly assigned to perindopril-indapamide or placebo. The primary endpoint was a composite of major macrovascular and microvascular disease. The effects of active treatment on outcomes were estimated in subgroups according to age: below 65, 65-74 and at least 75 years. RESULTS: During a mean 4.3-year follow-up, 1799 (16.1%) patients experienced a major event. Active treatment produced similar relative risk reductions for the primary outcome, major macrovascular disease, death and renal events across age groups (all P heterogeneity >0.3). Over 5 years, active treatment was estimated to prevent one primary outcome in every 21, 71 and 118 patients of at least 75, 65-74 and below 65 years, respectively. Similar patterns of benefits were observed for secondary outcomes. There were no differences in the tolerability between randomized allocations across age groups (all P heterogeneity >0.6) CONCLUSION: Routine administration of perindopril-indapamide lowers blood pressure safely and reduces the risk of major clinical outcomes in patients of at least 75 years with type 2 diabetes. The greater absolute benefits in older patients in this age group were not offset by an increased risk of side effects.

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TL;DR: The findings support the position that the number and specific combination of segments, angles, and walls interrogated are associated with differences in reproducibility, magnitude, and precision of progression of CIMT over time, and treatment effect.
Abstract: Background. Current ultrasound protocols to measure carotid intima-media thickness (CIMT) in trials rather differ. The ideal protocol combines high reproducibility with a high precision in the measurement of the rate of change in CIMT over time and with a precise estimate of a treatment effect. To study these aspects, a post-hoc analysis was performed using data from two randomized double-blind, placebo-controlled trials: one among 872 subjects with familial hypercholesterolemia (FH) and the other among 752 subjects with mixed dyslipidemia (MD), respectively. Participants were randomized to torcetrapib or placebo on top of optimal atorvastatin therapy.Methods. CIMT information was collected from the left and right carotid artery from two walls (the near and far wall) of three segments (common carotid, bifurcation, and internal carotid artery) at four different angles (right: 90, 120, 150, and 180 degrees on Meijer's carotid arc; left: 270, 240, 210, and 180 degrees, respectively). Based on combina...

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TL;DR: Moderate alcohol consumption (1-2 drinks/day) is not only associated with a reduced risk of vascular and all-cause death in a high risk patients with clinical manifestations of vascular disease, but also with reduced risks of non-fatal events like CHD, stroke and possibly amputations.

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TL;DR: Socio-demographic risk factors for non-clinical psychotic symptoms in the general population are also risk factorsFor a substantial part explained by an increase in other psychiatric symptoms.

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TL;DR: Moderate alcohol consumption is associated with a reduced risk of CHD among hypertensive women and light alcohol consumption tended to be related to a lower risk of stroke.
Abstract: AimThis study investigated the relation between alcohol consumption and the risk of cardiovascular disease (CVD) among 10 530-hypertensive women from the EPIC-NL cohort.Methods and resultsAlcohol consumption was assessed using a validated food-frequency questionnaire and participants were followed for occurrence of CVD. During 9.4 years follow-up, we documented 580 coronary heart disease (CHD) events and 254 strokes, 165 of which were ischemic. An inverse association (Ptrend = 0.009) between alcohol consumption and risk of CHD was observed with a multivariate-adjusted hazard ratio of 0.72 (95% confidence interval: 0.52-1.01) for those consuming 70-139.9 g alcohol/week compared to lifetime abstainers. Of different beverages, only red wine consumption was associated with a reduced risk of CHD. A U-shaped relation (P = 0.08) was observed for total stroke with a hazard ratio of 0.65 (0.44-0.95) for consuming 5-69.9 g alcohol/week compared with lifetime abstainers. Similar results were observed for ischemic st...

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TL;DR: The dynamics of mortality over follow-up time clearly differ between atherosclerotic diseases, located at different vascular beds, and the risk of death increases considerably over follow up time for PAD patients, and 5 years after first hospital admission the differences in risks of death between AMI- and P AD patients and between AMi- and ischemic stroke patients have largely attenuated.
Abstract: Most studies providing data on survival in patients with atherosclerosis only address a single disease site: heart, brain or legs. Therefore, our objective was to determine risk of death after first hospital admission for atherosclerotic disease located at different sites. A nationwide cohort of patients hospitalized for the first time for acute myocardial infarction (AMI), peripheral arterial disease of the lower extremities (PAD) or ischemic stroke was identified through linkage of national registers. The mortality rate in AMI patients was compared to mortality rate in ischemic stroke and PAD patients by estimating relative risks (with 95%CI). Cox's proportional hazard models were used to estimate sex differences in risk of death. Case fatality was high for ischemic stroke patients (men:21.0%, women:23.8%) and AMI patients (men:12.7%, women:20.9%) though low for PAD patients (men:2.4%, women:3.5%). The five-year risk of death was similar for male AMI compared to PAD patients (men: RR1.04; 95%CI 0.98-1.11). The risk of death for ischemic stroke patients remained the highest though the differences with AMI and PAD patients attenuated. The dynamics of mortality over follow-up time clearly differ between atherosclerotic diseases, located at different vascular beds. The risk of death increases considerably over follow-up time for PAD patients, and 5 years after first hospital admission the differences in risks of death between AMI- and PAD patients and between AMI- and ischemic stroke patients have largely attenuated. Clinicians should be aware of these dynamics of mortality over follow-up time to provide optimal secondary prevention treatment.

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TL;DR: Nutritional counselling by a dietician resulted in modest reductions in weight and waist circumference in overweight adults, which were sustained up to 12 months, which did not significantly enhance the effect on body weight.
Abstract: OBJECTIVE: To compare the effects of nutritional counselling with nutritional plus exercise counselling on body weight and waist circumference in overweight adults in a multidisciplinary primary care setting. METHODS: One hundred and thirty-four overweight adults (body mass index 28-35) were randomly assigned to individual counselling sessions by a dietician (D) or counselling sessions by a dietician plus physiotherapist (D + E) during 6 months with one follow-up session at 12 months. Outcomes were assessed at baseline, 6 and 12 months. Difference in changes of outcome measures between groups were analysed using generalized estimating equations. RESULTS: Weight reduced from baseline to 6 months in D [-2.2 (-3.1 to -1.4) kg] and D + E [-3.0 (-4.0 to -2.0) kg] and was sustained at 12 months [-2.0 (-3.1 to -1.4) kg and -3.1 (-4.5 to -1.6) kg, respectively]. The reduction in weight did not significantly differ between D and D + E (P = 0.48). In both groups, waist circumference decreased from baseline to 6 months [-2.1 (-3.3 to -0.8) cm for D; -3.7 (-5.1 to -2.3) cm for D + E] and was sustained at 12 months [-2.1 (-3.5 to -0.7) cm and -4.2 (-6.0 to -2.5) cm, respectively]. Participants in D + E tended to decrease their waist circumference more than those in D (P = 0.14). DISCUSSION: Nutritional counselling by a dietician resulted in modest reductions in weight and waist circumference in overweight adults, which were sustained up to 12 months. Adding exercise counselling by a physiotherapist did not significantly enhance the effect on body weight. Exercise counselling may, however, further improve waist circumference.

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TL;DR: Among nulliparous and initially normotensive women, the use of three simple clinical variables obtained routinely at the antenatal booking visit prior to 16 weeks, can accurately identify women at very low and very high risk of becoming hypertensive before 36 weeks of gestation.
Abstract: ObjectiveTo develop a prediction model for the occurrence of hypertension in pregnancy using clinical variables obtained routinely at the antenatal booking visit prior to 16 weeks gestation.MethodsWe studied 2334 nulliparous pregnant women participating in two population-based prospective cohort stu

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TL;DR: In this article, a prediction model was developed in 867 Dutch bakery workers (development set, prevalence of sensitization 13%) and included questionnaire items (candidate predictors) to detect sensitization to wheat allergens in bakery workers.

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TL;DR: The findings support the existing recommendations to routinely record an ECG in unselected hypertensive patients as the prevalence of relevant abnormalities is considerable and the number needed to screen with a routine ECG to prevent one death is lower than that in other widely accepted tests.
Abstract: Objective: Several guidelines for hypertension and cardiovascular risk management recommend an ECG in hypertensive patients to improve risk prediction. We estimated the prevalence of clinically relevant ECG abnormalities and the number needed to screen (NNS) with a routine ECG to prevent the occurrence of one death in the next 10 years conditional on adequate treatment and follow-up. Methods: The study population consisted of 866 hypertensive participants recruited from the Utrecht Health Project (UHP), a dynamic population study in Utrecht. Baseline measurements included an ECG and the risk factors that enable a Systematic COronary Risk Evaluation (SCORE) risk estimation for each participant. ECGs were interpreted using Modular ECG Analysis System for computerized recognition of ECG abnormalities. NNS to prevent one death was computed by the reciprocal of the prevalence of the ECG abnormalities multiplied by number needed to treat to prevent one death when the ECG abnormality is managed according to the prevailing clinical guidelines. Results: The population consisted of 54.2% men with a mean age of 53.2 years (SD 11.5). The prevalence of ECG abnormalities was 17.6 [n = 95% confidence interval (CI) 15.0-20.1]. Prevalence of atrial fibrillation or prior myocardial infarction was 2.1% (95%CI 1.1-3.0) and of other ECG abnormalities related to increased cardiovascular disease risk 15.4% (95%CI 13.1-17.9). NNS to prevent one death from cardiovascular disease within 10 years was estimated at 260 (95%CI 220-308). Conclusion: Our findings support the existing recommendations to routinely record an ECG in unselected hypertensive patients as the prevalence of relevant abnormalities is considerable and NNS to prevent one death is lower than that in other widely accepted tests.

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TL;DR: Predicting flour sensitisation by a simple questionnaire and score chart seems more effective at detecting work-related allergy than serology testing followed by clinical investigation in all immunoglobulin E class II-positive individuals.
Abstract: Identification of work-related allergy, particularly work-related asthma, in a (nationwide) medical surveillance programme among bakery workers requires an effective and efficient strategy. Bakers at high risk of having work-related allergy were indentified by use of a questionnaire-based prediction model for work-related sensitisation. The questionnaire was applied among 5,325 participating bakers. Sequential diagnostic investigations were performed only in those with an elevated risk. Performance of the model was evaluated in 674 randomly selected bakers who participated in the medical surveillance programme and the validation study. Clinical investigations were evaluated in the first 73 bakers referred at high risk. Overall 90% of bakers at risk of having asthma could be identified. Individuals at low risk showed 0.3–3.8% work-related respiratory symptoms, medication use or absenteeism. Predicting flour sensitisation by a simple questionnaire and score chart seems more effective at detecting work-related allergy than serology testing followed by clinical investigation in all immunoglobulin E class II-positive individuals. This prediction based stratification procedure appeared effective in detecting work-related allergy among bakers and can accurately be used for periodic examination, especially in small enterprises where delivery of adequate care is difficult. This approach may contribute to cost reduction.

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TL;DR: With the current ultrasound protocols it is possible to obtain a very high level of completeness in CIMT measurements and its relation with vascular risk factors, and segment-specific data indicated that in FH patients, completeness was less for the near wall of the left and right internal carotid artery as compared to other segments.
Abstract: Aim: Ultrasound protocols to measure carotid intima media thickness (CIMT) differ considerably with regard to the inclusion of the number of carotid segments and angles used. Detailed information on the completeness of CIMT information is often lacking in published reports, and at most, overall percentages are presented. We therefore decided to study the completeness of CIMT measurements and its relation with vascular risk factors using data from two CIMT intervention studies: one among familial hypercholesterolemia (FH) patients, the Rating Atherosclerotic Disease change by Imaging With A New CETP Inhibitor (RADIANCE 1), and one among mixed dyslipidemia (MD) patients, the Rating Atherosclerotic Disease change by Imaging With A New CETP Inhibitor (RADIANCE 2). Methods: We used baseline ultrasound scans from the RADIANCE 1 (n = 872) and RADIANCE 2 (n = 752) studies. CIMT images were recorded for 12 artery-wall combinations (near and far walls of the left and right common carotid artery (CCA), bifurcation (BIF) and internal carotid artery (ICA) segments) at 4 set angles, resulting in 48 possible measurements per patient. The presence or absence of CIMT measurements was assessed per artery-wall combination and per angle. The relation between completeness and patient characteristics was evaluated with logistic regression analysis. Results: In 89% of the FH patients, information on CIMT could be obtained on all twelve carotid segments, and in 7.6%, eleven segments had CIMT information (nearly complete 96.6%). For MD patients this was 74.6% and 17.9%, respectively (nearly complete: 92.5%). Increased body mass index and increased waist circumference were significantly (p = 0.01) related to less complete data in FH patients. For MD patients, relations were seen with increased waist circumference (p 98%). In MD patients, completeness was lower for the near wall of both the right and left carotid arteries: 86.0% and 90.8%, respectively, as compared to other segments (all >97%). Conclusions: With the current ultrasound protocols it is possible to obtain a very high level of completeness. Apart from the population studied, body mass index and waist circumference are important in achieving complete CIMT measurements

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TL;DR: Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements.
Abstract: OBJECTIVE: To investigate the interobserver and intraobserver agreements for the semiquantitative assessment of markers of subclinical cardiovascular disease as identified by routine care, diagnostic computed tomography (CT) of the chest, to improve the quality of reporting of these incidental findings. METHODS: Two observers independently evaluated 109 consecutive chest CT scans in routine care, clinical patients from one tertiary referral center. All nongated, contrast-enhanced scans were acquired on a 16-slice CT scanner. Images were scored for the presence of aortic wall abnormalities and calcifications of the coronary artery, the heart valves, the thoracic aorta, and the proximal supraaortic arteries. Furthermore, the presence of left ventricular scarring and elongation of the aorta were recorded. All markers were scored on a semiquantitative scale. Interobserver and intraobserver agreements are presented as weighted kappa and intraclass correlation coefficients. RESULTS: Interobserver and intraobserver agreements for individual markers were good to excellent, with weighted kappa coefficients of 0.54 to 0.89 for interobserver agreement and 0.55 to 0.96 for intraobserver agreement. CONCLUSIONS: Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements. Use of these definitions in clinical practice will enable a more standardized assessment and reporting of incidental findings in diagnostic chest CT.