Major adverse cardiovascular events in older emergency department patients presenting with non-cardiac medical complaints.

OBJECTIVE: The risk of major adverse cardiovascular events (MACE) for older emergency department (ED) patients presenting with non-cardiac medical complaints is unknown. To apply preventive measures timely, early identification of high-risk patients is incredibly important. We aimed at investigating the incidence of MACE within one year after their ED visit and the predictive value of high-sensitivity cardiac troponin T (hs-cTnT) and N­terminal pro-B-type natriuretic peptide (NT-proBNP) for subsequent MACE. METHODS: This is a substudy of a Dutch prospective cohort study (RISE UP study) in older (≥ 65 years) medical ED patients who presented with non-cardiac complaints. Biomarkers were measured upon ED arrival. Cox-regression analysis was used to determine the predictive value of the biomarkers, when corrected for other possible predictors of MACE, and area under the curves (AUCs) were calculated. RESULTS: Of 431 patients with a median age of 79 years, 86 (20.0%) developed MACE within 1 year. Both hs-cTnT and NT-proBNP were predictive of MACE with an AUC of 0.74 (95% CI 0.68-0.80) for both, and a hazard ratio (HR) of 2.00 (95% CI 1.68-2.39) and 1.82 (95% CI 1.57-2.11) respectively. Multivariate analysis correcting for other possible predictors of MACE revealed NT-proBNP as an independent predictor of MACE. CONCLUSION: Older medical ED patients are at high risk of subsequent MACE within 1 year after their ED visit. While both hs-cTnT and NT-proBNP are predictive, only NT-proBNP is an independent predictor of MACE. It is likely that early identification of those at risk offers a window of opportunity for prevention.

Metabolic syndrome and pre-eclampsia.

OBJECTIVE: To evaluate the association between different pre-eclampsia (PE) phenotypes and the development of metabolic syndrome postpartum, in order to identify the subgroup of formerly pre-eclamptic women with a worse cardiovascular risk profile requiring tailored postpartum follow-up. METHODS: This was a cohort study of 1102 formerly pre-eclamptic women in whom cardiovascular and cardiometabolic evaluation was performed at least 3 months postpartum. Women were divided into four subgroups based on PE resulting in delivery before 34 weeks (early-onset (EO)) or at or after 34 weeks (late onset (LO)) of gestation and whether they delivered a small-for-gestational-age (SGA) neonate. Metabolic syndrome was diagnosed as the presence of hyperinsulinemia along with two or more of: body mass index ≥ 30 kg/m2 ; dyslipidemia; hypertension; and microalbuminuria or proteinuria. Data were compared between groups using ANOVA after Bonferroni correction. Odds ratios (OR) were calculated using logistic regression to determine the association between metabolic syndrome and the four subgroups. We constructed receiver-operating characteristics curves and computed the area under the curve (AUC) to quantify the ability of different obstetric variables to distinguish between women who developed metabolic syndrome and those who did not. RESULTS: The prevalence of metabolic syndrome was higher in women with EO-PE and SGA (25.8%) than in those with EO-PE without SGA (14.7%) (OR 2.01 (95% CI, 1.34-3.03)) and approximately five-fold higher than in women with LO-PE with SGA (5.6%) (OR 5.85 (95% CI, 2.60-13.10)). In women with LO-PE, the prevalence of metabolic syndrome did not differ significantly between women with and those without SGA. Multivariate analysis revealed that a history of SGA, a history of EO-PE and systolic blood pressure at the time of screening are the best predictors of developing metabolic syndrome postpartum. The AUC of the model combining these three variables was 74.6% (95% CI, 70.7-78.5%). The probability of the presence of metabolic syndrome was calculated as: P = 1/(1 + e-LP ), where LP is linear predictor = -8.693 + (0.312 × SGA (yes = 1)) + (0.507 × EO-PE (yes = 1)) + (0.053 × systolic blood pressure). CONCLUSIONS: The incidence of metabolic syndrome postpartum was associated more strongly with EO-PE in combination with SGA as compared with LO-PE or EO-PE without SGA. Both time of onset of PE and fetal growth affect the risk of metabolic syndrome after a pre-eclamptic pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Spontaneous coronary artery dissections and associated predisposing factors: a narrative review.

Spontaneous coronary artery dissection (SCAD) represents around 25% of cases of acute coronary syndromes (ACS) in women aged 40-65 years who have few or no traditional cardiovascular risk factors. It is assumed that the incidence is underestimated, as the angiographic appearance of SCAD may often mimic atherosclerosis. This review aims to examine SCAD by focusing on the associated predisposing factors and precipitating stressors in this heterogeneous patient population, as well as the best treatment approach and the prognosis. Progressive knowledge has improved our current understanding of SCAD, but more awareness among clinicians is necessary. Recently, two position papers from the European Society of Cardiology (ESC) and the American Heart Association (AHA) have been released, which will be summarised in brief.

New diagnostic and treatment strategies in renal artery stenosis: a promising pursuit or disappointment foretold?

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

Determinants of DNA yield and purity collected with buccal cell samples.

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0 microg (median 54.3 microg; mean 82.2 microg +/- SD 92.6). The median UV 260:280 ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7 microg) than those from women (median 44.2 microg). Diuretic drug users had significantly lower purity (median 1.92) compared to other antihypertensive drug users (1.95). One technician obtained significantly lower DNA yields. Older age was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs was higher in men and DNA purity was associated with age and the use of diuretics.

Systemic inflammatory responses in dogs experimentally infected with Babesia canis; a haematological study.

A detailed haematological study of dogs that were infected with low, moderate or high numbers of Babesia canis-infected red blood cells was performed in an attempt to elucidate the pathogenesis early after B. canis infection. Results showed that upon infection the C-reactive protein (CRP) level in plasma increased prior to the detection of parasites in the blood indicative of an acute phase reaction. The response was further characterised by fever, fibrinogenaemia, thrombocytopenia and leucopoenia. Thrombocytopenia was associated with increased coagulation time. Infected dogs also developed life threatening hypotension, and dogs that were infected with the highest dose of B. canis-infected red blood cells had to be treated chemotherapeutically. Hypotension was associated with a reduced packed cell volume (PCV). This reduction of PCV correlated with reduced plasma creatinin concentration, suggesting that the plasma volume was increased, affecting both the erythrocyte and creatinin concentration in the plasma. Importantly, the onset of the response but not the dynamics of the response was dependent on the infectious dose i.e. curves obtained with different doses of infected erythrocytes appeared to be shifted in time but had a similar shape. This indicates that infection triggered a preset inflammatory response.

T64A polymorphism in beta3-adrenergic receptor gene (ADRB3) and coronary heart disease: a case-cohort study and meta-analysis.

OBJECTIVES: A missense mutation of the human ADRB3 gene replacing tryptophan with arginine at codon 64 (Trp64Arg) has been related to obesity, insulin resistance, earlier onset of noninsulin-dependent diabetes mellitus and hypertension. These findings may also suggest an increased risk of coronary heart disease (CHD). We therefore investigated the role of this polymorphism on the occurrence of acute myocardial infarction (AMI) and CHD in a population of healthy Dutch women. DESIGN: We performed a case-cohort study in a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model with an estimation procedure adapted for case-cohort designs to study the relationship between the polymorphism and AMI (n = 71) and CHD (n = 211). In addition, a meta-analysis of published studies was performed using a random effect model. RESULTS: Using the dominant model, carriers of the arginine allele (n = 222) compared to those with the more common genotype (n = 1508) were not at increased risk of AMI (hazard ratio = 1.60; 95% CI, 0.86-2.96) and for CHD (HR = 1.36; 95% CI, 0.92-2.02). We did not find any relationship using recessive and additive models, either. Our meta-analysis corroborated these findings by showing no significant association between the polymorphism and risk of CHD using different genetic models. CONCLUSIONS: Our study in combination with a meta-analysis of previous reports do not provide support for a role of missense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) at the human ADRB3 gene in CHD risk.

Compartmentalisation and zoning: the Dutch perspective.

The aim of the World Organisation for Animal Health (OIE) procedure of compartmentalisation is to contribute to safe trade in live animals and animal products. The fundamental requirement for its application is that the population considered for trade remains epidemiologically separate from populations of higher risk. Compartmentalisation makes use of a functional separation through management, taking into account all relevant epidemiological factors. In this paper, the authors begin by describing current (inter)national developments and actions in this field. Second, some sensitive issues are outlined where one internationally accepted view would help to implement compartmentalisation successfully in international trade. The OIE standards do not contain the procedure for assessing the biosecurity plan, which is crucial. The authors propose the use of a hazard analysis and critical control point system (HACCP) to determine the effectiveness of a biosecurity plan, taking account of all possible risks and potential disease entry points. This could be based on the model of the Codex Alimentarius Commission. Other issues discussed are the outbreak of disease close to a compartment, the role of certification agencies and non-compliance with the biosecurity plan.

['A new emperor, a new spirit']. / 'Een nieuwe keizer, een nieuwe geest'.

The editor in chief, J. van Gijn, has retired. His main emphasis on the generalist capacities of the physician and on meticulous anamnesis and thorough physical examination is as relevant as ever. However a new challenge is unfolding: how to serve the modern physician who was brought up with digital information and the Internet revolution, with relevant, independent, and objective medical information. The web presence of this journal (www.ntvg.nl) will be brought up to the level of the demanding modern physician. This will include the possibilities of e-learning, podcasts and web videos. The British mathematician and physicist Sir Roger Penrose argues in his book The emperor's new mind: concerning computers, minds, and the laws of physics that the human spirit will never be equalled or replaced by a computer. If he is right--which he probably is--the plans of the new editors should not be seen as a foreseeable algorithmic reaction to the digitalising world, but as a genuinely new perspective.

[Two-thirds of doctors are female, but ever still behind]. / Twee derde van de artsen vrouw, maar nog steeds op achterstand.

At present, two-thirds of the medical students in The Netherlands are women. However, the problems of combining a medical education with the responsibilities of motherhood, and the inaccessibility of medical top positions for women, are as serious as they were ten years ago at the 65th anniversary of the Dutch Association of Medical Women (VNVA). There is a serious need for medical education to become more 'woman-friendly'--and 'man-friendly' for that matter. For healthcare workers, it should be feasible to combine having children with a career. In addition, research into gender-specific health differences should be facilitated. Women, in particular, should take their responsibility in this respect, and be aware of the achievements of their pioneering predecessors. Last but not least: the Dutch Journal of Medicine needs to adapt. It needs to address a new audience, in which the male readers aged 50 and over have been largely replaced by female physicians in their thirties with children.

[Practical questions related to self-measurement of blood pressure]. / Praktische vragen bij het zelfmeten van de bloeddruk.

The results of self-measurements of blood pressure predict the risk of developing cardiovascular disease better than those of blood pressure measurements taken at the GP surgery or hospital. In spite of the increasing availability of devices for home measurement, exactly how, by whom, with what and when, blood pressure should be measured at home remains unclear. Self-measurement is to be recommended as a supplement to conventional blood pressure measurement, as, in this way, the white-coat effect and masked hypertension can be recognized. Self-measurement is only useful if it is carried using a validated, automatic, sphygmomanometer and measured in the correct way. It is essential that the patient be clearly instructed on how to do this. A limit for home measurement of 135/85 mmHg should be adhered to. When blood pressure measurements taken at home lead to a different conclusion than those taken at hospital or GP surgery (and if there is no white-coat or masked hypertension), it is recommended that the procedure be repeated. If after this, there is still a discrepancy between the results of these two methods of blood pressure measurement, ambulatory 24-hour blood pressure measurement will perhaps provide the definitive answer to the 'real' level of the patient's blood pressure.

[Hippocrates in the age of reality television]. / Hippocrates in het tijdperk van de 'reality-tv'.

At the end of their studies, physicians take the Hippocratic Oath. Medical and societal changes have meant that the oath has been altered over time. The oath still stipulates that the privacy of the patient should be respected. These days there is increased pressure on physicians and institutions to breach the duty of professional confidentiality. However, physicians themselves should also consider being more careful when talking about their patients outside the consulting room. They should definitely be aware oftheir responsibilities when participating in a reality series on television. In addition, medical information that is disclosed on Internet videos may negatively affect patients and physicians. Medical openness is commendable, but negligence may lead to loss of respect.

[The dawn of a smoke-free leisure industry in The Nederlands]. / Aan de vooravond van een rookvrije horeca in Nederland.

From the 1st of July 2008 the Dutch smoking ban for public spaces will be extended to hotels, restaurants and bars. The ban is a result of a 2003 Health Council report in which it was concluded that the annual incidence of deaths due to passive smoking is considerable. Based on these numbers, smoking in public spaces is prohibited since 2004. In a society where smoking in public spaces is prohibited, the harm of passive smoking will decrease. In this issue of The Nederlands Tijdschrit voor Geneeskunde (Dutch Journal of Medicine) a number of articles are dedicated to the subject of smoking.

Changes in fibrinolytic activity after angiotensin II receptor blockade in therapy-resistant hypertensive patients.

BACKGROUND: In hypertensive patients, the activated renin-angiotensin system induces a prothrombotic state resulting from imbalance between coagulation and fibrinolysis. Although blood pressure cannot be regulated in therapy-resistant hypertensive patients, they may still be responsive to medication that attenuates the renin-angiotensin system. OBJECTIVE: our objective was to study possible attenuating properties of angiotensin II type 1 receptor blockers (AT1RBs) on the prothrombotic state in therapy-resistant hypertensive patients, focusing on parameters of fibrinolysis and coagulation. METHODS: Fourteen therapy-resistant hypertensive patients received AT1RB eprosartan infusion (45 and 150 microg kg(-1)) (study group), and 33 therapy-resistant hypertensive patients received saline (0.9%) infusion (control group) prior to renal angiography. Baseline values of parameters of coagulation and fibrinolysis were set at 1.00, and relative changes were calculated. RESULTS: Plasminogen activator inhibitor type 1 (PAI-1) antigen showed non-significant decreases in both the study group (arterial 1.00-0.45, venous 1.00-0.42) and control group (arterial 1.00-0.84, venous 1.00-0.88). PAI-1 activity significantly decreased in the study group (arterial 1.00-0.72, venous 1.00-0.71) and control group (arterial 1.00-0.83, venous 1.00-0.94). In the study group, tissue-type plasminogen activator (t-PA) antigen decreased significantly (arterial 1.00-0.62, venous 1.00-0.67), whereas t-PA activity significantly increased (arterial 1.00-6.15, venous 1.00-2.66). In the control group, t-PA antigen remained unchanged. No changes were observed in blood pressure during and after infusion of eprosartan. CONCLUSION: Therapy-resistant hypertensive patients show beneficial changes in fibrinolytic activity after infusion of a non-pressor dose of AT1RB.

The Asp299Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis.

BACKGROUND: Recently, the common Asp299Gly polymorphism of the Toll-like receptor 4 (TLR-4) was found to be associated with a reduced incidence of acute myocardial infarction and carotid atherosclerosis. As TLR-4 signalling is causally involved in atherogenesis, the polymorphism was postulated to impart protection from atherosclerosis. To explore a potential atheroprotective effect, we studied the association between the Asp299Gly polymorphism and atherosclerosis in hypertensive patients undergoing angiography for suspected renovascular disease. METHODS: 140 hypertensive subjects underwent intraarterial digital subtraction angiography, during which the presence of atherosclerotic lesions was assessed at the level of the abdominal aorta and renal arteries. Extensiveness of disease was classified as follows: atherosclerosis confined to the abdominal aorta, unilateral renal artery stenosis or bilateral renal artery stenosis. Subsequently, genotyping for the +896 A>G (Asp299Gly) single nucleotide polymorphism was performed in all patients. In statistical analyses 17 patients were excluded because of incomplete data (n=3) or a diagnosis of fibromuscular disease (n=14). RESULTS: 21 patients were found heterozygous for the 299Gly allele, whereas none of the subjects were 299Gly homozygous (299Gly allele frequency 7.8%). The prevalence of the 299Gly allele in atherosclerotic patients was not different from the prevalence observed in subjects without atherosclerotic lesions (16.9 vs 15.5%, p=0.83). Moreover, 299Gly carriership was not associated with the extensiveness of (advanced) aortic atherosclerosis (p=0.64). CONCLUSION: Our results suggest that the Asp299Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.

[Measuring the blood pressure in both arms is subject to discussion]. / Meten van de bloeddruk aan beide armen onderwerp van discussie.

The recommendation to measure, at least once, the blood pressure in both arms is not without dispute. Several observations argue against such a recommendation. These include left-to-right asymmetry in cases of vascular rigidity and atherosclerotic lesions in both arms, and the variability of blood pressure. The latter may preclude any meaningful comparison between measurements taken in the left and right arm if these measurements are not obtained simultaneously.

[Hypertension as a source of cognitive regression, or dementia]. / Hypertensie als bron van cognitieve regressie, respectievelijk dementie.

Cognitive deterioration and its sequelae of vascular or Alzheimer's dementia is rapidly increasing all over the world. This is primarily caused by the worldwide increase of the ageing population. Additional causes may be sought in factors such as genetics and a habitually unhealthy life style. The significance of high blood pressure in the process leading to cognitive deterioration is relatively unknown. However, timely detection and treatment of hypertension seems to contribute to the preservation of cognition. Experience has shown that this applies in particular to dihydropyridine calcium antagonists. Medical care tends to make insufficient use of the existing possibilities for treating hypertension.

Ambulatory blood pressure, asymptomatic cerebrovascular damage and cognitive function in essential hypertension.

Prolonged exposure to elevated blood pressure (BP) can lead to both structural (white matter lesions (WML) or infarctions) and functional changes in the brain. We studied in previously diagnosed essential hypertensive individuals if diurnal BP variation and ambulatory BP (ABP) profile (daytime, night time and 24-h BP averages) were related to evidence of WML, the presence of 'silent' infarcts, and cognitive performance. A group of 86 patients (mean age 57.4+/-10 years, range 40-80) were first screened for hypertension-related organ damage and underwent 24-h ABP monitoring, magnetic resonance imaging (MRI) of the brain, and a comprehensive neurocognitive assessment. Age and ABP profile were related to more periventricular, but not subcortical, WML and to presence of lacunar infarctions on MRI. After correction for demographical group differences, no association was found between night time dipping of BP on the one hand and both WML load and cognitive parameters (verbal memory, sensorimotor speed, cognitive flexibility) on the other. The presence of lacunar infarctions, however, predicted lower performance on verbal memory. Furthermore, daytime and 24-h pulse pressure averages were associated with pWML, whereas systolic BP and mean arterial pressure (MAP) for daytime, night-time and 24-h periods were higher in patients with lacunar infarctions. Notwithstanding the large variability of WML in this sample, the evidence of a connection between diurnal BP variation and early target organ damage in the brain was not convincing. However, the ABP profile may be predictive of cerebral lesion type.

[The use of angiotensin converting enzyme (ACE) inhibitors during pregnancy clearly increases the risk of congenital malformations]. / Duidelijk verhoogd risico op congenitale afwijkingen door het gebruik van angiotensineconverterend-enzym(ACE)-remmers in de zwangerschap.

Recently, an important study was published concerning the possible teratogenic effects of angiotensin converting enzyme (ACE) inhibitors. Non-diabetic women who had used an ACE inhibitor during the first trimester of pregnancy had a significantly greater chance of giving birth to an infant with congenital malformations than women who had used no or other antihypertensive agents. The excess risk remained even after adjusting for several potential confounders. The results indicate that ACE inhibitors should not be prescribed to women who are likely to become pregnant during the course of treatment.

Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

BACKGROUND: The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. METHODS AND RESULTS: Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. CONCLUSIONS: Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.