D E Grobbee

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (869)3447.05 Total impact

  • European Journal of Preventive Cardiology 06/2014; · 3.90 Impact Factor
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    ABSTRACT: This paper presents a discussion of knowledge and awareness regarding prevention of functional decline in older hospitalized patients. Functional decline is experienced by 30-60% of the older hospitalized patients, resulting in decreased independence and other adverse health outcomes. One literature study and four cohort studies (total n = 1628) were conducted to develop and validate an instrument to identify older hospitalized patients at risk for functional decline. An evidence-based best practice was developed to improve the quality of care for older patients. This paper shows the relevance and the complexity of this problem and shows that patients at risk can be recognized by four simple questions. Due to their ability to observe and guide patients and their 24-h patient supervision, nurses should play a key role in strategies to prevent functional decline. Nurses should assess the geriatric needs in patients at risk and based on these initiate and coordinate multi-professional interventions. Given the growing number of older people in western society and the growing need for care, action to prevent functional decline cannot be withheld. Knowledge of the ageing process, implementation of an evidence-based programme and a multidisciplinary approach is a basic ingredient to prevent functional decline.
    International Journal of Nursing Practice 02/2014; 20(1):106-13. · 0.88 Impact Factor
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    ABSTRACT: Background The relationship between numerous risk factors and perioperative mortality after cardiovascular surgery has been studied extensively. While improved perioperative survival and fewer cardiovascular events have been related to statin therapy, its effect on long-term survival after aneurysm repair remains to be elucidated. The aim of this study is to determine the effect of statin therapy on long-term survival after open and endovascular aneurysm repair and to identify other cardiovascular and patient-related risk factors in this respect. Methods A post-hoc analysis of a randomized trial comparing open and endovascular abdominal aortic aneurysm repair was performed. In this multicenter trial, 351 patients were randomly assigned to undergo either open abdominal aortic aneurysm repair or endovascular repair. Patients who were on lipid-lowering medication at their inclusion in the trial (n = 135) were compared with those who were not (n = 216). Results During 6 years of follow-up, 118 (33.6%) patients died after randomization. Statin therapy, baseline characteristics, Society for Vascular Surgery/International Society for Cardiovascular Surgery risk factors, aneurysm size, reinterventions, antiplatelet or anticoagulant agents, and β-blockers were used to identify prognostic factors influencing survival. After identification of significant factors in a Kaplan-Meier analysis, a multivariable Cox regression analysis was applied. Statin therapy at inclusion in the trial was independently associated with better overall survival after open or endovascular aneurysm repair (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.8; P = .004). Statins were especially associated with fewer cardiovascular deaths (HR, 0.4; 95% CI, 0.2-0.9; P = .025). Several risk factors were associated with poor survival after open and endovascular aneurysm repair: age >70 (HR, 3.4; 95% CI, 2.2-5.0; P < .001), a history of cardiac disease at baseline (HR, 1.9; 95% CI, 1.3-2.8; P = .001), and moderate/severe tobacco use (HR, 1.7; 95% CI, 1.2-2.5; P = .004). Gender, aneurysm size, the need for reintervention, pulmonary disease, renal disease, carotid disease, hypertension, diabetes mellitus, antiplatelet or anticoagulant agents, and β-blockers were not significantly associated with impaired long-term survival (P > .05). Conclusions Despite the limitations of a post-hoc analysis of a prospectively maintained trial, we conclude that statin therapy at the beginning of the trial is independently associated with improved long-term survival after open or endovascular aneurysm repair, while age above 70 years, a history of cardiovascular disease, and tobacco use are associated with decreased long-term survival.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 01/2014; 59(1):39–44.e1. · 3.52 Impact Factor
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    ABSTRACT: Introduction Drug-induced cancer risk is of increasing interest. Both observational studies and data from clinical trials have linked several widely used treatments to cancer. When a signal for a potential drug-cancer association is generated, substantiation is required to assess the impact on public health before proper regulatory action can be taken. This paper aims to discuss challenges of exploring drug-associated cancer outcomes by post-hoc analyses of RCTs designed for other purposes. Methodological challenges to consider We set out to perform a post-hoc nested case-control analysis in the ADVANCE trial in order to examine the association between insulin use and cancer. We encountered several methodological challenges that made the results difficult to interpret, including short duration of exposure of interest, lack of power, and correlation between exposure and potential confounders. Considering these challenges, we concluded that using the data would not enlighten the discussion about insulin use and cancer risk and only serve to further complicate any understanding. Therefore, we decided to use our experience to illustrate methodological challenges, which need to be addressed when re-analysing trial data for cancer related outcomes. Conclusion Substantial amount of information on cancer outcomes is available from RCTs. Hence, making use of such data could save time and spare patients from inclusion in further trials. However, methodological challenges must be addressed to enhance the likelihood of reliable conclusions. Advantages of post-hoc analyses of RCTs include quality of data collected and sometimes randomisation to exposure of interest. Limitations include confounding and sample size, which is fixed to suit the purposes of the trial, insufficient duration of exposure and identification of underlying biological mechanisms relating treatment to cancer to formulate the most appropriate post-hoc study design.
    Current drug safety. 11/2013;
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    ABSTRACT: Background: a growing number of older patients undergo cardiac surgery. Some of these patients are at increased risk of post-operative functional decline, potentially leading to reduced quality of life and autonomy, and other negative health outcomes. First step in prevention is to identify patients at risk of functional decline. There are no current published tools available to predict functional decline following cardiac surgery.Objective: to validate the identification of seniors at risk-hospitalised patients (ISAR-HP), in older patients undergoing cardiac surgery.Design and methods: a multicenter cohort study in cardiac surgery wards of two university hospitals with follow-up 3 months after hospital admission. Inclusion criteria: consecutive cardiac surgery patients, aged ≥65. Functional decline was defined as a decline of at least one point on the Katz ADL Index at follow-up compared with preadmission status.Results: 475 patients were included, 16% of all patients and 20% of patients ≥70+ suffered functional decline. The amended prediction model predicted functional decline using four criteria: preadmission need for daily assistance in instrumental activities of daily living, use of a walking device, need for assistance in travelling and no education after age 14. Area under the receiver operating curve for patients ≥70 it was 0.73. For the amended ISAR-HP sensitivity, specificity, positive and negative predictive values were 85, 48, 29 and 93%, respectively.Conclusions: the amended ISAR-HP used in older cardiac surgery patients showed good discriminative values at score ≥1, supporting the generalisability of this prediction model for this patient group.
    Age and Ageing 11/2013; · 3.82 Impact Factor
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    ABSTRACT: Angiotensin-Receptor-Blockers (ARBs) have multiple effects that may contribute to their efficacy on renal/cardiovascular outcomes. We developed and validated a risk score that incorporated short-term changes in multiple risk markers to predict the ARB effect on renal/cardiovascular outcomes. The score was used to predict renal/cardiovascular risk at baseline and month-6 in the ARB treatment arm of the RENAAL trial. The net risk difference at these time-points indicated the estimated long-term renal/cardiovascular treatment effect. Predicted relative risk reductions (RRR) based on multiple markers were close to observed RRR for renal (RRRpredicted: 30.1% vs. RRRobserved: 21.8%; p=0.44) and cardiovascular outcomes (RRRpredicted: 9.4% vs. RRRobserved: 9.2%; p=0.98), and markedly more accurate than predicted RRR based on changes in single-markers. The score was validated in an independent ARB trial. Predictions of long-term renal/cardiovascular ARB effects are more accurate when considering short-term changes in multiple risk markers, challenging the use of single-markers to establish drug efficacy.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 25 September 2013 doi:10.1038/clpt.2013.191.
    Clinical Pharmacology &#38 Therapeutics 09/2013; · 6.85 Impact Factor
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    ABSTRACT: Recognition of myocardial injury after non-cardiac surgery is difficult, since strong analgesics (e.g. opioids) can mask anginal symptoms, and ECG abnormalities are subtle or transient. Thorough knowledge of the pathophysiological mechanisms is therefore essential. These mechanisms can be subdivided into four groups: type I myocardial infraction (MI), type II MI, non-ischaemic cardiac pathology, and non-cardiac pathology. The incidence of type I MI in patients with a clinical suspicion of perioperative acute coronary syndrome (ACS) is 45-57 %. This percentage is higher in patients with a high likelihood of MI such as patients with ST-elevation ACS. Of note, the generalisability of this statement is limited due to significant study limitations. Non-ischaemic cardiac pathology and non-cardiac pathology should not be overlooked as a cause of perioperative myocardial injury (PMI). Especially pulmonary embolism and dysrhythmias are a common phenomenon, and may convey important prognostic value. Implementation of routine postoperative troponin assessment and accessible use of minimally invasive imaging should be considered to provide adequate individualised therapy. Also, addition of preoperative imaging may improve the stratification of high-risk patients who may benefit from preoperative or perioperative interventions.
    Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 08/2013; · 1.41 Impact Factor
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    ABSTRACT: AimsCommon carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures.Methods and resultsWe combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)].Conclusion We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.
    European Heart Journal 08/2013; 34(30):2368-80. · 14.10 Impact Factor
  • Hipertensión y Riesgo Vascular. 07/2013; 17(1):36–37.
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    ABSTRACT: BACKGROUND: Heart failure (HF) is a serious complication and often the cause of death in adults with congenital heart disease (CHD). Therefore, our aims were to determine the frequency of HF-admissions, and to assess risk factors of first HF-admission and of mortality after first HF-admission in adults with CHD. METHODS: The Dutch CONCOR registry was linked to the Hospital Discharge Registry and National Mortality Registry to obtain data on HF-admissions and mortality. Risk factors for both HF-admission and mortality were assessed using Cox regression models. RESULTS: Of 10,808 adult patients (49% male), 274 (2.5%) were admitted for HF during a median follow-up period of 21years. The incidence of first HF-admission was 1.2 per 1000 patient-years, but the incidence of HF itself will be higher. Main defect, multiple defects, and surgical interventions in childhood were identified as independent risk factors of HF-admission. Patients admitted for HF had a five-fold higher risk of mortality than patients not admitted (hazard ratio (HR)=5.3; 95% confidence interval 4.2-6.9). One- and three-year mortality after first HF-admission were 24% and 35% respectively. Independent risk factors for three-year mortality after first HF-admission were male gender, pacemaker implantation, admission duration, non-cardiac medication use and high serum creatinine. CONCLUSIONS: The incidence of HF-admission in adults with CHD is 1.2 per 1000 patient-years. Mortality risk is substantially increased after HF-admission, which emphasises the importance to identify patients at high risk of HF-admission. These patients might benefit from closer follow-up and earlier medical interventions. The presented risk factors may facilitate surveillance.
    International journal of cardiology 04/2013; · 6.18 Impact Factor
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    ABSTRACT: AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.
    Diabetologia 04/2013; · 6.49 Impact Factor
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    ABSTRACT: Increase of factor VIII activity (FVIII) after physical exercise has been reported in healthy subjects and small-scale studies in patients with coagulopathies. The aim was to study whether moderate and mild haemophilia A patients are able to increase their endogenous FVIII activity levels by physical activity. We studied changes in FVIII activity levels after high-intensity exercise in 15 haemophilia A patients, 20-39 years, eight with moderate, seven with mild haemophilia. Patients cycled until volitional exhaustion, blood samples were drawn before and 10 min after the exercise test. FVIII activity increased 2.5 times (range 1.8-7.0 times), for both severities. Absolute increases were markedly different: median 7 IU dL(-1) (range 3-9 IU dL(-1) ) in patients with moderate, compared to 15 IU dL(-1) (range 6-62 IU dL(-1) ) in mild haemophilia patients. VWF and VWFpp increased independently of severity; median 50% (range 8-123%) and median 165% (range 48-350%), respectively, reflecting acute release of VWF. These observations may be used to promote high-intensity activities before participating in sports for moderate and mild haemophilia A patients, to reduce bleeding risk. Further studies are warranted to fully appreciate the clinical significance of exercise on different levels of intensity in patients with mild and moderate haemophilia A.
    Haemophilia 03/2013; · 3.17 Impact Factor
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    ABSTRACT: IntroductionWe recently developed and validated in existing trials a novel algorithm (PRE score) to predict long-term drug efficacy based on short-term (month-6) drug-induced changes in multiple risk markers. To show the value of the PRE score for ongoing and planned clinical trials, we here report the predicted long-term cardio-renal efficacy of aliskiren in type 2 diabetes, which was investigated in the ALTITUDE trial, but unknown at the time this study was conducted.Methods We established the relation between multiple risk markers and cardio-renal endpoints (as defined in ALTITUDE) using a background database from past clinical trials. The short-term effect of aliskiren on multiple risk markers was taken from the AVOID trial. A PRE score was developed by multivariate Cox analysis in the background population and was then applied to the baseline and month-6 measurements of the aliskiren treatment arm of the AVOID trial to predict cardio-renal risk. The net risk difference at these time-points, after correction for placebo effects, was taken to indicate the estimated long-term cardio-renal risk change.ResultsBased on the PRE score, we predicted that aliskiren treatment in ALTITUDE would confer a relative risk change of -7.9% (95% CI -2.5 to -13.4) for the cardio-renal endpoint, a risk change of -5.1% (-1.2 to -9.0) for the CV endpoint and a non-significant risk change of -19.9% (-42.1 to +2.1) for the renal endpoint.ConclusionsPRE score estimations suggested that aliskiren has only a marginal additive protective effect on cardio-renal endpoints. These predictions were validated by the results of the ALTITUDE trial, confirming the potential of the PRE score to prospectively predict drug efficacy on cardio-renal outcomes.
    European journal of preventive cardiology. 03/2013;
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    ABSTRACT: Objective: Functional decline is a major threat to independency, progressing into functional limitations and eventually leading to disability. Chronic diseases, especially cardiovascular diseases, are important determinants of functional limitations and disability. Vascular damage exits long before it is clinically manifest and can have adverse effects on health, physical and cognitive functioning. The objective was to investigate the association between non-invasive atherosclerosis measures and physical functioning in older men. Design: Prospective cohort study. Setting: The study was conducted in the general community. Participants: 195 independently living older men. Measurements: Atherosclerosis was measured by intima media thickness (CIMT) of the common carotid artery using ultrasonography and assessment for presence of atherosclerotic plaques. Physical functioning was measured by isometric handgrip strength and leg extensor strength using a hand held dynamometer, lower extremity function using the physical performance score and ability to perform activities of daily life using the modified Stanford Health Assessment Questionnaire. Linear regression analysis was performed to estimate the associations between CIMT or plaques and physical functioning. Results: After adjustment for confounders, higher baseline CIMT was associated with lower isometric handgrip strength at follow up (βCIMT =-7.21, 95% CI[-13.64;-0.77]). No other associations were found between CIMT and physical functioning. In addition, no associations were found for the presence of plaques and physical functioning either at baseline, or at follow-up. Conclusion: Atherosclerosis, as measured by higher CIMT, is related to a lower isometric handgrip strength at follow-up, but no further associations with physical functioning were found in this longitudinal study among independently living older men.
    The Journal of Nutrition Health and Aging 01/2013; 17(1):97-104. · 2.39 Impact Factor
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    ABSTRACT: BACKGROUND: An international collaboration of investigators will assess the benefits and risks of fixed dose combination (FDC) based care compared with usual care in populations at high risk of cardiovascular disease (CVD). Several trials are being conducted, as the effectiveness and economic impact of a FDC-based strategy may vary substantially between countries, given the varying influence of the health-care system within which the intervention is delivered. METHODS: Individual patient data (IPD) will be provided by participating trials for combined IPD meta-analysis. RESULTS: Primary outcomes will include self-reported current use of antiplatelet, statin, and combination (>/=2) blood pressure lowering therapies at 12months, and change in systolic blood pressure (SBP) and LDL cholesterol from baseline to 12months. Non-inferiority margins of 3mmHg for SBP and 0.3mmol/L for LDL cholesterol have been pre-specified. Secondary outcomes will include change in cholesterol fractions, diastolic blood pressure and creatinine from baseline to 12months, quality of life, new onset diabetes mellitus, mortality (cardiovascular, non-cardiovascular and all cause) and a composite outcome of cardiovascular events (including all coronary heart disease events, heart failure events leading to death or requiring hospital admission, cerebrovascular events and peripheral arterial events). CONCLUSION: The SPACE group of trials will assess, in a variety of healthcare settings, whether a FDC strategy for delivery of preventive medication has the potential to significantly improve prevention of cardiovascular disease in patients at high risk.
    Int J Cardiol. 01/2013;
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    ABSTRACT: IMPORTANCE: Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment. OBJECTIVE: To assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). DESIGN, SETTING, AND PARTICIPANTS: The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012. INTERVENTIONS: Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002). MAIN OUTCOMES AND MEASURES: Adherence to medication (defined as self-reported use of antiplatelet, statin, and >/=2 BP-lowering medications) and changes in SBP and LDL-C from baseline. RESULTS: At baseline, mean BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86% vs 65%; relative risk [RR] of being adherent, 1.33; 95% CI, 1.26-1.41; P < .001) with concurrent reductions in SBP (-2.6 mm Hg; 95% CI, -4.0 to -1.1 mm Hg; P < .001) and LDL-C (-4.2 mg/dL; 95% CI, -6.6 to -1.9 mg/dL; P < .001) at the end of the study. Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36%), adherence at the end of study was 77% vs 23% (RR, 3.35; 95% CI, 2.74-4.09; P < .001 for interaction), SBP was reduced by 4.9 mm Hg (95% CI 7.3-2.6 mm Hg; P = .01 for interaction), and LDL-C was reduced by 6.7 mg/dL (95% CI, 10.5-2.8 mg/dL; P = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 [5%] in the FDC group and 35 [3.5%] in the usual care group; RR, 1.45; 95% CI, 0.94-2.24; P=.09) between the groups. CONCLUSIONS AND RELEVANCE: Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057537.
    JAMA The Journal of the American Medical Association 01/2013; 310(9):918-29. · 29.98 Impact Factor
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    ABSTRACT: BACKGROUND: Moderate haemophilia is the rarest form of haemophilia. This study aims to assess short-and long-term outcome, including its association with treatment, in patients with moderate haemophilia. MATERIAL AND METHODS: Seventy-five patients with moderate haemophilia (1-5% factor VIII/factor IX activity), without a history of inhibitors, treated at the van Creveldkliniek, Utrecht (NL) were included in the study. Life-long data on bleeding and treatment were collected. Joints were evaluated using the Haemophilia Joint Health Score. Adults completed questionnaires on activity (HAL) and quality of life (SF-36, EQ5D). RESULTS: The median age of the patients was 37 years (IQR 23-52 years) and haemophilia A was diagnosed in 89%. Bleeding frequency was low: the median annual bleeding rate was 2.0 bleeds/year (IQR 0.8-3.7 bleeds/year), including a median of 0 joint bleeds/year (IQR 0.8-3.7 bleeds/year). Joint function was good: 82% scored <10 out of 126 points of the Haemophilia Joint Health Score (HJHS). Nevertheless, 29% of patients with moderate haemophilia had a history of prophylaxis, because of a high bleeding frequency. Median age at first joint bleed was 4.8 years (IQR 3.5-8.5). Use of prophylaxis was more associated with age at first joint bleed (P <0.01) than with baseline factor activity (P =0.12). Most patients (52%) who suffered their first joint bleed before the age of 5 years required prophylaxis later in life. DISCUSSION: The majority of patients with moderate haemophilia have few bleeds and complications; however, a considerable subset of patients with a more severe bleeding pattern need prophylactic treatment. These latter patients may be identified by the onset of joint bleeding before the age of 5 years.
    Blood transfusion = Trasfusione del sangue 11/2012; · 1.86 Impact Factor
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    ABSTRACT: BACKGROUND: Since the introduction of prophylaxis, physicians have tried to convert the clinical phenotype of severe haemophilia (SH) into that of moderate haemophilia (MH), but the outcome of patients with SH has never been compared to that of patients with MH. MATERIAL AND METHODS: The outcome of 80 patients with SH on long-term, intermediate dose prophylaxis was compared to that of 40 patients with MH in a single-centre study. Data on treatment history, activities (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D), and 5-year bleeding and clotting factor consumption were collected for patients born between 1970-1995. RESULTS: The median age of the patients was 24 years (IQR 18-30). All patients with SH received long-term prophylaxis, which was started at a median age of 4.8 years (IQR 3.2-6.2). Among the patients with MH, ten (25%) received prophylaxis, starting at a median age of 10.8 years (IQR 3.8-13.8). The annual number of bleeds, including joint bleeds, was significantly higher in patients with SH (median 2.0 joint bleeds/year, IQR=0.8-3.7) than in patients with MH (median 0.8 joint bleeds/year, IQR=0-1.2). Due to greater use of prophylaxis, the annual clotting factor consumption of SH patients (median 2120 IU/kg; IQR 1514-2768), was higher than that of MH patients (median 133 IU/kg; IQR 49-468). Patients with SH showed slightly but significantly more loss of clinical function (assessed by the Haemophilia Joint Health Score): a median of 8 points (IQR 3-15) vs a median of 2 points, IQR 0-6). Quality of life, as measured by the SF-36, EQ5D and physical activity, was similar between patients with disease of different severity, as well as compared to that of the general population. DISCUSSION: When comparing unselected cohorts, the bleeding pattern of patients with SH does not appear to be fully converted to that of the milder bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although activities and quality of life were similar.
    Blood transfusion = Trasfusione del sangue 11/2012; · 1.86 Impact Factor
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    Pierre-Jean Touboul, Diederick E Grobbee, Hester den Ruijter
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    ABSTRACT: Carotid intima-media thickness assessed by ultrasonography of carotid arteries is a safe, non-expensive, feasible and accurate method for detecting early signs of atherosclerosis and carotid intima-media thickness and change in carotid intima-media thickness over time reflect cardiovascular disease risk. Technical aspects impact on the measurement, variability and interpretation of carotid intima-media thickness. These include device aspects, inter- and intra-sonographer variability and the ultrasound protocol used. The mean common carotid intima-media thickness and the mean maximum common carotid intima-media thickness are the most widely used carotid intima-media thickness measurements. Common carotid intima-media thickness values of around 0.5 mm are considered 'normal' in young adults. Values are higher in men than in women, in African-Americans than Caucasians and increase with age. Carotid intima-media thickness values at or above the 75th percentile of a reference population indicate increased cardiovascular risk. Guidelines differ in their recommendations for the use of carotid intima-media thickness measurements for risk assessment in primary prevention because evidence suggesting that it improves upon conventional risk scores is inconsistent. Carotid intima-media thickness is frequently used in clinical trials as a surrogate endpoint for cardiovascular events on the assumption that regression or slowed progression of carotid intima-media thickness, induced by cardiovascular risk interventions, reflects a reduction in cardiovascular events. However, further data are required to confirm this linear relationship. No international guidelines exist on the use of carotid intima-media thickness as a research tool. Quality control in acquisition, measurement and interpretation of carotid intima-media thickness are important considerations and the carotid intima-media thickness protocol used should be determined by the research question under investigation.
    European journal of preventive cardiology. 08/2012; 19(2 Suppl):18-24.
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    ABSTRACT: Serum IGF-binding protein 2 (IGFBP2) concentrations are reduced in obese humans and increase after a prolonged period of fasting. We investigated the association between IGFBP2 levels and mortality together with other factors that are related to IGFBP2, including the metabolic syndrome and physical function. A prospective observational study at a clinical research center of 403 independently living elderly men (aged 73-94 years). Mortality was registered during 8.6 years of follow-up. Physical performance score (PPS), grip strength (GS), and bone mineral density (BMD) were measured. The measurements taken a baseline were: IGF1; IGFBP1, -2, and -3; IGF1 bioactivity; triiodothyronine (T(3)); and reverse T(3). Further, BMI, insulin sensitivity, cholesterol, inflammatory markers, and albumin levels were also measured. During the follow-up, 180 men died. Higher PPS, GS, and BMD were independently related to a reduced mortality (hazard ratio (HR)=0.87/point, 95% confidence interval (95% CI)=0.82-0.91, P<0.001; HR=0.96/kp, 95% CI 0.94-0.98, P<0.001; and HR=0.21/(g/cm(2)), 95% CI 0.07-0.61, P<0.01). Higher serum IGFBP2 levels were strongly related to mortality (HR=2.26/(mg/l), 95% CI 1.57-3.27, P<0.001). This was independent of comorbidity, physical function, IGF1 bioactivity, and other somatotropic parameters, including BMI and the metabolic syndrome. In addition, IGFBP2 levels were higher in subjects with nonthyroidal illness, and higher IGFBP2 levels were significantly associated with lower albumin concentrations. Despite the strong relationship between high IGFBP2 and low physical function, both were strongly and independently related to increased 8-year mortality in elderly men. IGFBP2 may be a useful biomarker integrating the nutritional status, as well as the biological effects of GH, IGF1, and insulin.
    European Journal of Endocrinology 05/2012; 167(1):111-7. · 3.14 Impact Factor

Publication Stats

26k Citations
3,447.05 Total Impact Points


  • 1998–2014
    • University Medical Center Utrecht
      • • Julius Center for Health Sciences and Primary Care
      • • Department of Epidemiology
      Utrecht, Utrecht, Netherlands
    • University of Münster
      • Institute of Epidemiology and Social Medicine
      Münster, North Rhine-Westphalia, Germany
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2011
    • University of Washington Seattle
      • Division of Medical Genetics
      Seattle, WA, United States
  • 2003–2011
    • University of Groningen
      • • Department of Clinical Pharmacology
      • • Department of Cardiology
      Groningen, Province of Groningen, Netherlands
  • 2009
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2008
    • University of Wuerzburg
      Würzburg, Bavaria, Germany
  • 1997–2008
    • Universiteit Utrecht
      • • Division of Pharmacoepidemiology and Pharmacotherapy
      • • Julius Centre for Health Sciences and Primary Care
      • • Department of Epidemiology
      • • University Medical Center Utrecht
      Utrecht, Provincie Utrecht, Netherlands
    • Imperial College London
      Londinium, England, United Kingdom
  • 2000–2007
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
    • SOCAR Research SA
      Nyon, Vaud, Switzerland
    • St. Antonius Ziekenhuis
      • Department of Cardiology
      Nieuwegen, Utrecht, Netherlands
    • University of Auckland
      Окленд, Auckland, New Zealand
  • 2005–2006
    • National Institute for Public Health and the Environment (RIVM)
      Utrecht, Utrecht, Netherlands
    • Spaarne Ziekenhuis
      • Department of Pediatrics
      Hoofddorp, North Holland, Netherlands
  • 1999–2006
    • Wageningen University
      • Division of Human Nutrition
      Wageningen, Provincie Gelderland, Netherlands
    • Leiden University Medical Centre
      • Department of Molecular Cell Biology
      Leiden, South Holland, Netherlands
    • National Heart, Lung, and Blood Institute
      • Division of Cardiovascular Sciences (DCVS)
      Maryland, United States
    • University of Utah
      • Department of Internal Medicine
      Salt Lake City, UT, United States
  • 1986–2006
    • Erasmus Universiteit Rotterdam
      • • Department of Internal Medicine
      • • Department of Medical Informatics
      • • Department of Epidemiology
      Rotterdam, South Holland, Netherlands
  • 2001–2004
    • University of Pretoria
      • • Department of Clinical Epidemiology
      • • Department of Internal Medicine
      Pretoria, Gauteng, South Africa
  • 2002
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
  • 1989–2001
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1997–1998
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 1996
    • Leiden University
      Leyden, South Holland, Netherlands
    • University of Amsterdam
      • Department of Clinical Epidemiology and Biostatistics
      Amsterdam, North Holland, Netherlands
    • Transnationale Universiteit Limburg
      Box Elder, South Dakota, United States
  • 1995
    • Maastricht University
      • Biochemie
      Maastricht, Provincie Limburg, Netherlands
  • 1994
    • Academisch Medisch Centrum Universiteit van Amsterdam
      Amsterdamo, North Holland, Netherlands