The growing number of older patients presenting to Emergency Departments (EDs) requires better risk stratification to guide treatment and dispositiondecisions. Therefore, it is essential to... Show moreThe growing number of older patients presenting to Emergency Departments (EDs) requires better risk stratification to guide treatment and dispositiondecisions. Therefore, it is essential to understand the effect of age on the associations between physiological variables and outcomes. More importantly, most risk tools are not age or sex adjusted and are not based on a statistical approach. An age and sex adjusted risk tool could improve risk stratification in the ED.This thesis is divided into three parts and has four aims, regarding ageadjusted interpretation of physiological variables for risk stratification in ED patients, developing a new age- and sex-adjusted risk tool for the hospital, and describing potential bias if risk tools are used for comparing the quality of care among departments. Show less
Kooijmans, E.C.M.; Pal, H.J.H. van der; Pluijm, S.M.F.; Bresters, D.; Dulmen-den Broeder, E. van; Heiden-van der Loo, M. van der; ... ; Dutch LATER Study Grp 2022
Purpose: To evaluate the prevalence of and risk factors for hypertension in child-hood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. Methods: In the Dutch... Show morePurpose: To evaluate the prevalence of and risk factors for hypertension in child-hood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. Methods: In the Dutch Childhood Cancer Survivor Study LATER cohort part 2 renal study, 1024 CCS >= 5 years after diagnosis, aged >= 18 years at study participation, treated between 1963 and 2001 with nephrectomy, abdominal radiotherapy, total body irradiation (TBI), cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide (>= 1 g/m(2) per single dose or >= 10 g/m(2) total) or haematopoietic stem cell transplantation participated and 500 controls from Lifelines. Hypertension was defined as blood pressure (BP) (mmHg) systolic >= 140 and/or diastolic >= 90 or receiving medication for diagnosed hypertension. At the study visit, the CKD-EPI 2012 equation including creatinine and cystatin C was used to estimate the glomerular filtration rate (GFR). Multivariable regression analyses were used. For ambulatory BP monitoring (ABPM), hypertension was defined as BP daytime: systolic >= 135 and/or diastolic >= 85, night time: systolic >= 120 and/or diastolic >= 70, 24-h: systolic >= 130 and/or diastolic >= 80. Outcomes were masked hypertension (MH), white coat hypertension and abnormal nocturnal dipping (aND). Results: Median age at cancer diagnosis was 4.7 years (interquartile range, IQR 2.4-9.2), at study 32.5 years (IQR 27.7-38.0) and follow-up 25.5 years (IQR 21.4-30.3). The prevalence of hypertension was comparable in CCS (16.3%) and controls (18.2%). In 12% of CCS and 17.8% of controls, hypertension was undiagnosed. A decreased GFR (< 60 ml/min/1.73 m(2)) was associated with hypertension in CCS (OR 3.4, 95% CI 1.4-8.5). Risk factors were abdominal radiotherapy >= 20 Gy and TBI. The ABPM-pilot study (n Z 77) showed 7.8% MH, 2.6% white coat hypertension and 20.8% aND. Conclusion: The prevalence of hypertension was comparable among CCS who were treated with potentially nephrotoxic therapies compared to controls, some of which were undiagnosed. Risk factors were abdominal radiotherapy >= 20 Gy and TBI. Hypertension and decreased GFR were associated with CCS. ABPM identified MH and a ND. (C) 2022 The Author(s). Published by Elsevier Ltd. Show less
Background The Framingham hypertension risk score is a well-known and simple model for predicting hypertension in adults. In the current study, we aimed to assess the predictive ability of this... Show moreBackground The Framingham hypertension risk score is a well-known and simple model for predicting hypertension in adults. In the current study, we aimed to assess the predictive ability of this model in a Middle Eastern population.MethodsWe studied 5423 participants, aged 20-69years, without hypertension, who participated in two consecutive examination cycles of the Tehran Lipid and Glucose Study (TLGS). We assessed discrimination based on Harrell's concordance statistic (c-index) and calibration (graphical comparison of predicted vs. observed). We evaluated the original, recalibrated (for intercept and slope), and revised (for beta coefficients) models.ResultsOver the 3-year follow-up period, 319 participants developed hypertension. The Framingham hypertension risk score performed well in discriminating between individuals who developed hypertension and those who did not (c-index=0.81, 95% CI: 0.79-0.83). Initially, there was a systematic underestimation of the original risk score (events predicted), which was readily corrected by a simple model revision.ConclusionsThe revised Framingham hypertension risk score can be used as a screening tool in public health and clinical practice to facilitate the targeting of preventive interventions in high-risk Middle Eastern people. Show less
The fact that most healthcare resources are spend on a small subgroup of patients with an unfavourable prognosis has long been recognized. Therefore change is needed in terms of an improved... Show moreThe fact that most healthcare resources are spend on a small subgroup of patients with an unfavourable prognosis has long been recognized. Therefore change is needed in terms of an improved identification of patients with an unfavourable prognosis, early in their treatment course, which may facilitate proactive approaches to improve outcomes. We discussed two conceptually distinct constructs of predictors of prognosis in order to improve the identification of patients with an unfavourable prognosis. First, the level of control of the chronic condition as a predictor could reflect to some extent the presence of a multitude of other risk factors. Second, information on early treatment response had better predictive ability for long-term outcomes and so acts as a proxy for treatment effectiveness. Treatment effectiveness depends on different aspects e.g. adequateness of initial treatment and/or drugs, the mutual trust between clinician and patient and behavioral aspects such as treatment adherence. Treatment response adds an insight that can be acted upon; guiding personalized decisions in the treatment plan. In conclusion, this thesis leads to improvement of personalized medicine and thereby could increase the efficient use of healthcare resources, with the early identification of patients at risk of an unfavourable prognosis. Show less
Colafella, K.M.M.; Neves, K.B.; Montezano, A.C.; Garrelds, I.M.; Veghel, R. van; Vries, R. de; ... ; Versmissen, J. 2020
Aims Although effective in preventing tumour growth, angiogenesis inhibitors cause off-target effects including cardiovascular toxicity and renal injury, most likely via endothelin (ET)-1 up... Show moreAims Although effective in preventing tumour growth, angiogenesis inhibitors cause off-target effects including cardiovascular toxicity and renal injury, most likely via endothelin (ET)-1 up-regulation. ET-1 via stimulation of the ETA receptor has pro-hypertensive actions whereas stimulation of the ETB receptor can elicit both pro- or antihypertensive effects. In this study, our aim was to determine the efficacy of selective ETA vs. dual ETA/B receptor blockade for the prevention of angiogenesis inhibitor-induced hypertension and albuminuria.Methods and results Male Wistar Kyoto (WKY) rats were treated with vehicle, sunitinib (angiogenesis inhibitor; 14 mg/kg/day) alone or in combination with macitentan (ETA/B receptor antagonist; 30 mg/kg/day) or sitaxentan (selective ETA receptor antagonist; 30 or 100 mg/kg/day) for 8 days. Compared with vehicle, sunitinib treatment caused a rapid and sustained increase in mean arterial pressure of similar to 25 mmHg. Co-treatment with macitentan or sitaxentan abolished the pressor response to sunitinib. Sunitinib did not induce endothelial dysfunction. However, it was associated with increased aortic, mesenteric, and renal oxidative stress, an effect that was absent in mesenteric arteries of the macitentan and sitaxentan co-treated groups. Albuminuria was greater in the sunitinib- than vehicle-treated group. Co-treatment with sitaxentan, but not macitentan, prevented this increase in albuminuria. Sunitinib treatment increased circulating and urinary prostacyclin levels and had no effect on thromboxane levels. These increases in prostacyclin were blunted by co-treatment with sitaxentan.Conclusions Our results demonstrate that both selective ETA and dual ETA/B receptor antagonism prevents sunitinib-induced hypertension, whereas sunitinib-induced albuminuria was only prevented by selective ETA receptor antagonism. In addition, our results uncover a role for prostacyclin in the development of these effects. In conclusion, selective ETA receptor antagonism is sufficient for the prevention of sunitinib-induced hypertension and renal injury. Show less
Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study,... Show moreEpidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (beta = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (beta = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (beta = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses. Show less
Objective: The objective of this study was to determine the clinical relevance of postcarotid endarterectomy hypertension (PEH) by investigating the effect of PEH on hospital length of stay (LOS)... Show moreObjective: The objective of this study was to determine the clinical relevance of postcarotid endarterectomy hypertension (PEH) by investigating the effect of PEH on hospital length of stay (LOS) and by investigating short-term and long-term complications of PEH. In addition, risk factors for PEH were determined.Methods: A single-center retrospective cohort study was performed. Demographic, preoperative, intraoperative, and postoperative outcomes of 192 patients undergoing carotid endarterectomy were evaluated. Outcomes were compared between patients with PEH and patients without PEH. PEH was defined as an acute systolic blood pressure (SBP) rise >170 mm Hg or persistent SBP >150 mm Hg on the ward and leading to the consultation of an internist. The overall survival and event-free survival were compared using a Kaplan-Meier analysis and a Cox regression analysis. A multivariate logistic regression analysis was performed to determine risk factors for PEH.Results: PEH developed in 44 of 192 patients (25%). Preoperative hypertension (SBP >150 mm Hg) was determined to be a risk factor for PEH (odds ratio, 3.3; 95% confidence interval [CI], 1.6-6.9). Hospital LOS was prolonged in patients with PEH compared with patients without PEH (median LOS of 5 days vs 3 days, respectively; P <.001). No difference in the occurrence of ischemic neurologic events or rebleeding during hospitalization was observed (P =.58 and P =.72, respectively). Cardiovascular and ischemic neurologic events during follow-up did not occur more often in patients with PEH than in patients without PEH (P =.46). There was no difference in mortality between the PEH and non-PEH groups (hazard ratio, 1.6; 95% CI, 0.6-4.3). The same applies to the event-free survival (hazard ratio, 0.77; 95% CI, 0.4-1.7). Combined event-free survival for stroke and myocardial infarction was 92% (95% CI, 87%-97%) at 2 years for patients without PEH and 86% (95% CI, 74%-98%) at 2 years for patients with PEH (P =.25). Event-free survival for mortality was 90% (95% CI, 85%-96%) at 2 years for patients without PEH and 94% (95% CI, 86%-100%) at 2 years for patients with PEH (P =.36).Conclusions: Patients with PEH had a significant increase in hospital LOS. However, adverse short-term and long-term events did not occur more often in patients with PEH. High preoperative SBP was identified as a risk factor for PEH; no other demographic and clinical variables were associated with PEH. Show less
Worldwide, raised blood pressure is estimated to affect 35-40% of the adult population and is a main conditioning factor for cardiovascular diseases and stroke. Animal models of hypertension have... Show moreWorldwide, raised blood pressure is estimated to affect 35-40% of the adult population and is a main conditioning factor for cardiovascular diseases and stroke. Animal models of hypertension have provided great advances concerning the pathophysiology of human hypertension, as already shown for the deoxycorticosterone-salt treated rat, the Dahl-salt sensitive rat, the Zucker obese rat and the spontaneously hypertensive rat (SHR). SHR has been widely used to study abnormalities of the brain in chronic hypertension. This review summarises present and past evidence that in the SHR, hypertension causes hippocampal tissue damage which triggers a pro-inflammatory feedforward cascade affecting this vulnerable brain region. The cascade is driven by mineralocorticoid receptor (MR) activation responding to endogenous corticosterone rather than aldosterone. Increased MR expression is a generalised feature of the SHR which seems to support first the rise in blood pressure. Then oxidative stress caused by vasculopathy and hypoxia further increases MR activation in hippocampal neurons and glia cells, activates microglia activation and pro-inflammatory mediators, and down-regulates anti-inflammatory factors. In contrast to MR, involvement of the glucocorticoid receptor (GR) in SHR is less certain. GR showed normal expression levels and blockage with an antagonist failed to reduce blood pressure of SHR. The findings support the concept that MR:GR imbalance caused by vasculopathy causes a switch in MR function towards a proverbial "death" receptor. Show less
Ikonomidis, I.; Aboyans, V.; Blacher, J.; Brodmann, M.; Brutsaert, D.L.; Chirinos, J.A.; ... ; Metra, M. 2019
Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent... Show moreVentricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo-arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis. Show less
With increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year... Show moreWith increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year-olds when they have multimorbidity, polypharmacy or frailty. Large trials showed that lowering BP in >60-year-olds is beneficial and lowers the risk for myocardial infarction, stroke and all-cause mortality. However, these trials lack generalizability and typically excluded multimorbid patients that are frail. At the same time, observational studies rose concerns about lowering BP too much since there are several cohort studies showing a reverse association of low BP and increased mortality especially in >75-year-olds. The general aim of this thesis is to increase the scientific knowledge about the effects of treating hypertension in >75-year-olds with frailty. This thesis has three aims: 1) to measure the prevalence of polypharmacy in older patients; 2) to test for an association between low SBP and mortality, cognitive function, daily functioning, and QoL in older patients under antihypertensive treatment; and 3) to understand the role that frailty plays in GP decisions about treating hypertension in old age across countries and see if those differences can be explained by country-specific cardiovascular disease burden and life expectancy. Show less
Cardiovascular disease (CVD) is the leading cause of death worldwide despite the successful development of several pharmaceutical interventions of which statin therapy is the dominating lipid... Show moreCardiovascular disease (CVD) is the leading cause of death worldwide despite the successful development of several pharmaceutical interventions of which statin therapy is the dominating lipid-lowering treatment option. Atherosclerosis, a chronic inflammatory disease of multifactorial origin, is a dominant contributor to the development of CVD. The research described in this thesis provides evidence for anti-atherogenic effects of several innovative pharmaceutical interventions that are currently being investigated in clinical trials, targeting hypertension and hypercholesterolemia, more specifically high low-density lipoprotein-cholesterol (LDL-C) and low high-density lipoprotein-cholesterol (HDL-C), as risk factors for CVD. Our results further support additional benefit of these treatment strategies in combination with statin treatment which is currently the __gold standard__ therapy for the treatment of CVD. Most of these lipid-modifying treatment strategies affect both LDL-C and HDL-C and we demonstrate that the beneficial effects of these treatment strategies predominantly derive from their non-HDL-C/LDL-C-lowering abilities. Nonetheless, results from preclinical studies and clinical trials support the notion that treatment strategies aimed at improving HDL function and raising apolipoprotein A-I may also inhibit the development of atherosclerosis and reduce the prevalence of CVD. Show less
Berg, I.J.; Semb, A.G.; Heijde, D. van der; Kvien, T.K.; Hisdal, J.; Olsen, I.C.; ... ; Provan, S.A. 2014
