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.

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.

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.

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.

No effect of rosuvastatin on left ventricular hypertrophy in patients with hypertension: a prospective randomised open-label study with blinded endpoint assessment.

BACKGROUND: This study tested the hypothesis that statins may reduce left ventricular hypertrophy (LVH) in patients with hypertension and LVH. METHOD: A prospective randomised open-label study with blinded endpoints assessment was performed in 142 patients. Inclusion criteria were hypertension, left ventricular ejection fraction ≥50% and echocardiographic determined LVH, defined as a left ventricular mass index (LVMI) of ≥ 100 g/m(2) in women and ≥ 116 g/m(2) in males. Patients were randomised between rosuvastatin 20mg once daily vs control. For each patient an echocardiogram and blood samples were obtained. These tests were repeated after 6 months. RESULTS: Baseline characteristics: mean age was 62 ± 11year and 62 (44%) were male. In both groups, there was a non-significant reduction in LVMI: 118 ± 22 to 111 ± 19 g/m(2) in the control group and 118 ± 21 to 114 ± 22 in the rosuvastatin group (p=0.376 for the comparison between rosuvastatin and control after 6 months). After six months, LDL-cholesterol was reduced from 3.5 ± 1.0 to 2.1 ± 1.2 mmol/L (40% reduction) in the rosuvastatin group and remained unchanged in the control group (3.5 ± 0.9 vs 3.6 ± 0.9 mmol/L. Hs-CRP decreased more with rosuvastatin compared to control (-38% vs -15%, p=0.006) There was no significant reduction in NT-pro-BNP levels after 6 months. CONCLUSION: Rosuvastatin does not reduce LVH despite a large LDL reduction in patients with hypertension and LVH.

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.

Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis.

BACKGROUND: Several imaging techniques may reveal calcification of the arterial wall or cardiac valves. Many studies indicate that the risk for cardiovascular disease is increased when calcification is present. Recent meta-analyses on coronary calcification and cardiovascular risk may be confounded by indication. Therefore, this meta-analysis was performed with extensive subgroup analysis to assess the overall cardiovascular risk of finding calcification in any arterial wall or cardiac valve when using different imaging techniques. METHODS AND RESULTS: A meta-analysis of prospective studies reporting calcifications and cardiovascular end-points was performed. Thirty articles were selected. The overall odds ratios (95% confidence interval [CI]) for calcifications versus no calcifications in 218,080 subjects after a mean follow-up of 10.1 years amounted to 4.62 (CI 2.24 to 9.53) for all cause mortality, 3.94 (CI 2.39 to 6.50) for cardiovascular mortality, 3.74 (CI 2.56 to 5.45) for coronary events, 2.21 (CI 1.81 to 2.69) for stroke, and 3.41 (CI 2.71 to 4.30) for any cardiovascular event. Heterogeneity was largely explained by length of follow up and sort of imaging technique. Subgroup analysis of patients with end stage renal disease revealed a much higher odds ratio for any event of 6.22 (CI 2.73 to 14.14). CONCLUSION: The presence of calcification in any arterial wall is associated with a 3-4-fold higher risk for mortality and cardiovascular events. Interpretation of the pooled estimates has to be done with caution because of heterogeneity across studies.

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.

The contribution of six polymorphisms to cardiovascular risk in a Dutch high-risk primary care population: the HIPPOCRATES project.

This study was designed to examine the contribution of six polymorphisms to the occurrence of cardiovascular disease (CVD) in a Dutch primary care population with a high prevalence of cardiovascular risk factors. In this cross-sectional case-control study, 232 patients with CVD and 571 event-free controls were studied. Patients were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656rpt), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Univariate and multivariate odds ratios (ORs) were calculated to assess the relationship between genotypes and CVD. Receiver operating characteristic (ROC) analysis was used to quantify the contribution of the polymorphisms to the prediction of CVD. No differences in either genotype or allele frequencies were found between CVD cases and controls. Multivariate analyses, corrected for multiple testing according to Bonferroni, showed significant protective associations for the T-allele of AGT (OR=0.55 (0.34-0.84)) and for the T-allele of ADD1 (OR=0.52 (0.31-0.82)). ROC analysis showed only a very small improvement of CVD risk prediction by adding the six polymorphisms to a model with traditional risk factors. Our data suggest that a major attribution of the six polymorphisms to the cardiovascular risk prediction in a primary care population such as HIPPOCRATES is unlikely.

[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.

[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.

[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.

[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.

['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.

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.

[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.