Autonomic regulation in different hypertensive phenotypes - the HELIUS study.

Background: Hypertension can be classified into different phenotypes based on systolic and diastolic blood pressure (BP) that carry a different prognosis and may therefore be differently associated with sympathetic activity. We assessed the association between cardiac autonomic function determined from continuous finger BP recordings and hypertensive phenotypes. Methods: We included 10,221 individuals aged between 18-70 years from the multi-ethnic HELIUS study. Finger BP was recorded continuously for 3-5 minutes from which cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) were determined. Hypertension was classified into isolated systolic (ISH; ≥140/<90), diastolic (IDH; <140/≥90) and combined systolic and diastolic hypertension (SDH; ≥140/≥90). Differences were assessed after stratification by age (younger: ≤40, older: >40 years) and sex, using regression with correction for relevant covariates. For xBRS, values were log-transformed. Results: In younger adults with ISH, xBRS was comparable to normotensive individuals in men (ratio 0.92; 95%CI 0.84-1.01) and women (1.00; 95%CI 0.84-1.20), while xBRS was significantly lower in IDH and SDH (ratios between 0.67 and 0.80). In older adults, all hypertensive phenotypes had significantly lower xBRS compared to normotensives. We found a similar pattern for HRV in men, while in women HRV did not differ between phenotypes. Conclusions: In younger men and women ISH is not associated with a shift towards increased sympathetic control, while IDH and SDH in younger and all hypertensive phenotypes in older participants were associated with increased sympathetic control. This suggests that alterations in autonomic regulation could be a contributing factor to known prognostic disparities between hypertensive phenotypes.

Hypertension can be classified into different phenotypes based on systolic and diastolic blood pressure (BP) that carry a different prognosis. Impaired autonomic regulation is important in the pathogenesis of hypertension and independently associated with adverse cardiovascular outcomes.We analyzed 3-5 minutes continuous non-invasive finger blood pressure recordings performed in over 10.000 individuals participating in the HELIUS cohort study. From these measurements, short term heart rate variability (HRV) and cross correlation baroreflex sensitivity (xBRS) were determined using an automatic algorithm.In our analysis we observed pronounced differences in the relation between autonomic regulation and hypertensive phenotypes that depend on age and sex.Younger men and women (age 18-40 years) with isolated systolic hypertension had similar values for xBRS and HRV compared to normotensives, while isolated diastolic hypertension was associated with a shift towards increased sympathetic control. In contrast to our findings in younger individuals, all hypertensive phenotypes were associated with increased sympathetic control in older participants (age 40-70 years).This supports earlier studies showing prognostic differences and suggests that alterations in sympathovagal balance could be a contributing factor to the disparities between phenotypes.

Automated analysis of finger blood pressure recordings provides insight in determinants of baroreflex sensitivity and heart rate variability-the HELIUS study.

Sympathovagal balance is important in the pathogenesis of hypertension and independently associated with mortality. We evaluated the value of automated analysis of cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) and its relationship with clinical covariates in 13,326 participants from the multi-ethnic HELIUS study. Finger blood pressure (BP) was continuously recorded, from which xBRS, standard deviation of normal-to-normal intervals (SDNN), and squared root of mean squared successive difference between normal-to-normal intervals (RMSDD) were determined. A subset of 3356 recordings > 300 s was used to derive the minimally required duration by comparing shortened to complete recordings, defined as intraclass correlation (ICC) > 0.90. For xBRS and SDNN, 120 s and 180 s were required (ICC 0.93); for RMSDD, 60 s (ICC 0.94) was sufficient. We included 10,252 participants (median age 46 years, 54% women) with a recording > 180 s for the regression. xBRS, SDNN, and RMSDD decreased linearly up to 50 years of age. For xBRS, there was a signification interaction with sex, with for every 10 years a decrease of 4.3 ms/mmHg (95%CI 4.0-4.6) for men and 5.9 ms/mmHg (95%CI 5.6-6.1) for women. Using splines, we observed sex-dependent nonlinearities in the relation with BP, waist-to-hip-ratio, and body mass index. Future studies can help unravel the dynamics of these relations and assess their predictive value. Panel 1 depicts automatic analysis and filtering of finger BP recordings, panel 2 depicts computation of xBRS from interpolated beat to beat data of systolic BP and interbeat interval, and (IBI) SDNN and RMSDD are computed directly from the filtered IBI dataset. Panel 3 depicts the results of large-scale analysis and relation of xBRS with age, sex, blood pressure and body mass index.

Reference ranges of anti-Müllerian hormone and interaction with placental biomarkers in early pregnancy: the Generation R Study, a population-based prospective cohort study.

Objective: The primary objective of this study is to establish maternal reference values of anti-Müllerian hormone (AMH) in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is to explore the association between AMH and placental biomarkers. Design: This study was embedded in the Generation R Study, an ongoing population-based prospective cohort study from early pregnancy onwards. Setting: City of Rotterdam, the Netherlands, out of hospital setting. Patients: In 5806 women, serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5-17.2). Intervention(s): None. Main outcome measures: Maternal AMH levels in early pregnancy and its association with placental biomarkers, including human chorionic gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFLT), and placental growth factor (PLGF). Results: A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of the placental biomarkers hCG and sFLT in early pregnancy. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels. Conclusion: In this large study, we show that AMH levels in early pregnancy decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT, and PLGF suggests a better placental development with lower vascular resistance in mothers with higher AMH levels. Hence, AMH might be useful in predicting adverse pregnancy outcomes due to impaired placental development.

The position of renal denervation in treatment of hypertension: an expert consensus statement.

Hypertension is an important risk factor for cardiovascular disease. In the Netherlands, there are approximately 2.8 million people with hypertension. Despite treatment recommendations including lifestyle changes and antihypertensive drugs, most patients do not meet guideline-recommended blood pressure (BP) targets. In order to improve BP control and lower the risk of subsequent cardiovascular events, renal sympathetic denervation (RDN) has been introduced and studied as a non-pharmacological approach. While early data on the efficacy of RDN showed conflicting results, improvements in treatment protocols and study design resulted in robust new evidence supporting the potential of the technology to improve patient care in hypertensive subjects. Recently, 5 randomised sham-controlled trials demonstrated the safety and efficacy of the technology. Modelling studies have further shown that RDN is cost-effective in the Dutch healthcare setting. Given the undisputable disease burden along with the shortcomings of current therapeutic options, we postulate a new, clearly framed indication for RDN as an adjunct in the treatment of hypertension. The present consensus statement summarises current guideline-recommended BP targets, proposed workup and treatment for hypertension, and position of RDN for those patients with primary hypertension who do not meet guideline-recommended BP targets (see central illustration).

Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study.

INTRODUCTION: We aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We included 55 Dutch, 127 South-Asian Surinamese, 92 African Surinamese, 62 Ghanaian, 74 Turkish and 88 Moroccan origin participants with T2DM from the HEalthy LIfe in an Urban Setting study. Using linear regression analyses, we investigated differences in urinary monocyte chemoattractant protein-1 (MCP-1) and heparanase-1 (HPSE-1) levels across ethnic minorities compared with Dutch. Associations between the urinary markers and albuminuria (albumin:creatinine ratio (ACR)) was investigated per ethnicity. RESULTS: Urinary MCP-1 levels were higher in the Moroccan participants (0.15 log ng/mmol, 95% CI 0.05 to 0.26) compared with Dutch after multiple adjustments. Urinary HPSE-1 levels were lower in the African Surinamese and Ghanaian participants compared with the Dutch, with a difference of -0.16 log mU/mmol (95% CI -0.29 to -0.02) in African Surinamese and -0.16 log mU/mmol (95% CI -0.31 to -0.00) in Ghanaian after multiple adjustments. In all ethnic groups except the Dutch and Ghanaian participants, MCP-1 was associated with ACR. This association remained strongest after multiple adjustment in South-Asian and African Surinamese participants, with an increase in log ACR of 1.03% (95% CI 0.58 to 1.47) and 1.23% (95% CI 0.52 to 1.94) if log MCP-1 increased 1%. Only in the Dutch participants, an association between HPSE-1 and ACR was found, with increase in log ACR of 0.40% (95% CI 0.04 to 0.76) if log HPSE-1 increased 1%. CONCLUSIONS: We found ethnic differences in urinary MCP-1 and HPSE-1 levels, in a multi-ethnic cohort of participants with T2DM. In addition, we found ethnic differences in the association of MCP-1 and HPSE-1 levels with albuminuria. These findings suggest differences in renal inflammation across ethnic groups.

Differences in the prevalence of intermediate hyperglycaemia and the associated incidence of type 2 diabetes mellitus by ethnicity: The HELIUS study.

AIMS: We aimed to describe differences in the prevalence of intermediate hyperglycaemia (IH) between six ethnic groups. Moreover, to investigate differences in the association of the classifications of IH with the incidence of T2DM between ethnic groups. METHODS: We included 3759 Dutch, 2826 African Surinamese, 1646 Ghanaian, 2571 Turkish, 2691 Moroccan and 1970 South Asian Surinamese origin participants of the HELIUS study. IH was measured by fasting plasma glucose (FPG) and HbA1c. We calculated age-, BMI and physical-activity-adjusted prevalence of IH by sex, and calculated age and sex-adjusted hazard ratios (HR)for the association between IH and T2DM in each ethnic group. RESULTS: The prevalence of IH was higher among ethnic minority groups (68.6-41.7%) than the Dutch majority (34.9%). The prevalence of IH categories varied across subgroups. Combined increased FPG and HbA1c was most prevalent in South-Asian Surinamese men (27.6%, 95 %CI: 24.5-30.9%), and in Dutch women (4.2%, 95 %CI: 3.4-5.1%). The HRs for T2DM for each IH-classification did not differ significantly between ethnic groups. HRs were highest for the combined classification, e.g., HR = 8.1, 95 %CI: 2.5-26.6 in the Dutch. CONCLUSION: We found a higher prevalence of IH in ethnic minority versus majority groups, but did not find evidence for a differential association of IH with incident T2DM.

Intestinal microbiota and diabetic kidney diseases: the Role of microbiota and derived metabolites inmodulation of renal inflammation and disease progression.

Diabetic kidney disease (DKD) represents a growing public health burden and is the leading cause of end-stage kidney diseases. In recent years, host-gut microbiota interactions have emerged as an integral part for host homeostasis. In the context of nephropathies, mounting evidence supports a bidirectional microbiota-kidney crosstalk, which becomes particularly manifest during progressive kidney dysfunction. Indeed, in chronic kidney disease (CKD), the "healthy" microbiota structure is disrupted and intestinal microbes produce large quantities of uremic solutes responsible for renal damage; on the other hand, the uremic state, fueled by reduced renal clearance, causes shifts in microbial metabolism and composition, hence creating a vicious cycle in which dysbiosis and renal dysfunction are progressively worsened. In this review, we will summarize the evidence from clinical/experimental studies concerning the occurrence of gut dysbiosis in diabetic and non-diabetic CKD, discuss the functional consequences of dysbiosis for CKD progression and debate putative therapeutic interventions targeting the intestinal microbiome.

Soluble syndecan-1 and glycosaminoglycans in preeclamptic and normotensive pregnancies.

Preeclampsia, an important cause of maternal and fetal morbidity and mortality, is associated with increased sFLT1 levels and with structural and functional damage to the glycocalyx contributing to endothelial dysfunction. We investigated glycocalyx components in relation to preeclampsia in human samples. While soluble syndecan-1 and heparan sulphate were similar in plasma of preeclamptic and normotensive pregnant women, dermatan sulphate was increased and keratan sulphate decreased in preeclamptic women. Dermatan sulphate was correlated with soluble syndecan-1, and inversely correlated with blood pressure and activated partial thromboplastin time. To determine if syndecan-1 was a prerequisite for the sFlt1 induced increase in blood pressure in mice we studied the effect of sFlt1 on blood pressure and vascular contractile responses in syndecan-1 deficient and wild type male mice. The classical sFlt1 induced rise in blood pressure was absent in syndecan-1 deficient mice indicating that syndecan-1 is a prerequisite for sFlt1 induced increase in blood pressure central to preeclampsia. The results show that an interplay between syndecan-1 and dermatan sulphate contributes to sFlt1 induced blood pressure elevation in pre-eclampsia.

[Case of refractory cardiogenic shock due to venlafaxine overdose : illustration of the support with veno-arterial extracorporeal membrane oxygenation]. / Choc cardiogénique réfractaire lié à une intoxication volontaire en venlafaxine : illustration de l'intérêt de l'ECMO veino-artérielle.

Venlafaxine is a widely prescribed antidepressant drug acting as a reuptake inhibitor of serotonin and noradrenaline. An overdose of venlafaxine can cause cardiovascular toxicity and cardiogenic shock can occur. A 32-year-old man ingested 12g of sustained-release venlafaxine in a suicidal attempt and developed within 24h acute heart failure with refractory cardiogenic shock requiring support by ECMO. The blood toxicology showed persistence of high levels of venlafaxine at day 10. The patient fully recovered and showed normal cardiac function at 3-months follow-up.

La venlafaxine est un antidépresseur largement prescrit agissant comme inhibiteur de recapture de la sérotonine et de la noradrénaline. Un surdosage en venlafaxine peut engendrer une toxicité cardiovasculaire allant jusqu'à l'état de choc cardiogénique. Un homme de 32 ans a ingéré 12 g de venlafaxine sous une forme à libération prolongée dans une tentative de suicide et a développé en 24 heures une insuffisance cardiaque aiguë avec choc cardiogénique réfractaire nécessitant un support hémodynamique par ECMO. La toxicologie sanguine a montré la persistance de niveaux élevés de venlafaxine au jour 10. Le patient s'est ensuite complètement rétabli et présentait une fonction cardiaque normale 3 mois après l'épisode.

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.

Health literacy and hypertension outcomes in a multi-ethnic population: the HELIUS study.

BACKGROUND: Hypertension disproportionately affects ethnic minority groups. Although health literacy may play role in these ethnic inequalities, little is known about the extent to which health literacy affects hypertension prevalence, awareness, treatment and control in different ethnic groups. Therefore, we assessed these associations in a multi-ethnic population. METHODS: Baseline data from the HELIUS study were used including participants of Dutch (n = 1948), South-Asian Surinamese (n = 2054) and African Surinamese (n = 1932) origin aged 18-70 years, who lived in Amsterdam, the Netherlands, were fluent in Dutch and underwent health literacy assessment through the Rapid Estimate of Adult Literacy in Medicine-Dutch (REALM-D). The REALM-D was categorized either as low (<60 sumscore) or adequate (≥60 sumscore) health literacy. Participants completed questionnaires and underwent physical examination. RESULTS: After adjusting for confounding variables, Dutch [odds ratio (OR) 2.02; 95% confidence interval (CI), 1.11-3.64] and African Surinamese (OR 1.36; 1.03-1.79) with low health literacy were more likely than those with adequate health literacy to have hypertension, whereas in South-Asian Surinamese this association was not significant. No significant associations were found between health literacy and hypertension awareness, treatment and control in any of the ethnic groups. CONCLUSION: Findings indicate that health literacy is associated with hypertension prevalence in selected ethnic groups, but not with hypertension awareness, treatment and control. Targeting health literacy might be an entry point for tackling ethnic inequalities in hypertension prevalence. To substantially reduce these inequalities, further research is needed to explore other factors and pathways through which health literacy may impact hypertension outcomes in different ethnic groups.

IgG4:IgG RNA ratio differentiates active disease from remission in granulomatosis with polyangiitis: a new disease activity marker? A cross-sectional and longitudinal study.

OBJECTIVES: An important limitation in granulomatosis with polyangiitis (GPA) is the lack of disease activity markers. Immunoglobulin G4-positive (IgG4+) B cells and plasma cells are implicated in the pathogenesis of GPA. We hypothesized that the presence of these cells in peripheral blood could serve as disease activity parameter in GPA. METHODS: We included 35 proteinase 3-antineutrophil cytoplasmic antibodies-positive patients with GPA in a cross-sectional study. Active disease was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 3 (n = 15), remission as BVAS of 0 (n = 17), and low disease activity (LDA) as BVAS of 1-2 and clinical remission (n = 3). Healthy subjects (n = 10), patients with systemic lupus erythematosus (n = 24), and patients with rheumatoid arthritis (n = 19) functioned as control subjects. An additional longitudinal study was performed in ten patients with GPA. Using a validated qPCR test, we measured the IgG4:IgG RNA ratio in all groups and compared the results with known biomarkers. RESULTS: The median qPCR score was higher in active GPA (21.4; IQR 12.1-29.6) than in remission/LDA (3.3; IQR 1.6-5.6) (Mann-Whitney U test, p < 0.0001) and outperformed other known disease activity parameters in detecting activity. A cutoff qPCR score of 11.2% differentiated active disease from remission/LDA accurately (AUC 0.993). The qPCR test correlated well with the BVAS (Spearman r = 0.77, p < 0.0001). In the longitudinal study, a decrease in BVAS correlated with qPCR score reduction (paired t test, p < 0.05). CONCLUSIONS: The IgG4:IgG RNA ratio in GPA accurately distinguishes active disease from remission and correlates well with disease activity in these single-center studies. If these results are confirmed in larger longitudinal studies, this test might help to steer treatment decisions in patients with GPA.

[Limits to the treatment of hypertension]. / Grenzen aan de behandeling van hypertensie.

According to the 2011 Dutch guideline on Cardiovascular risk management 1 in 5 hypertensive patients are eligible for blood pressure lowering treatment. The Dutch guideline recommends striving for a systolic blood pressure (SBP) of < 140 mmHg in adult patients who have no cardiovascular disease or diabetes mellitus, while the recent American guideline now recommends an SBP target value of < 130 mmHg for all adult patients. An important reason for using a stricter SBP target value are the results of randomised studies and meta-analyses that looked at the effect of intensive antihypertensive therapy on the risk of mortality and cardiovascular disease. Based on the literature, there appears to be sufficient evidence that intensive antihypertensive therapy (SBP target value of < 130 mmHg) is useful in patients with cardiovascular disease and in patients with high cardiovascular risk. Currently, there is insufficient evidence that intensive antihypertensive therapy is useful in patients who have diabetes mellitus or who are over 80 years old.

Prevalence and reproducibility of differences between home and ambulatory blood pressure and their relation with hypertensive organ damage.

Home and ambulatory blood pressure (BP) better predict cardiovascular disease than office BP, but are not interchangeable. We hypothesised that home BP may be higher than office BP because of anticipatory reactions to self-measurement and studied prevalence and reproducibility of incremental differences between home and daytime ambulatory BP and their relation with hypertensive organ damage. A total of 176 participants (mean age 57.1±12.8 years, 43.2% female) measured their BP for 2 weeks and received a 24-h ambulatory BP in between. Hypertensive organ damage was assessed by urinary albumin-to-creatinine ratio and electrocardiographic criteria for left ventricular hypertrophy. Thresholds of 10/5 and 20/10 mm Hg were used to define relevant systolic/diastolic differences between home and ambulatory BP. A higher home compared to ambulatory BP was present in 92 (52.3%) and 35 (19.1%) participants, while lower home BP values were present in 36 (20.4%) and 8 (4.5%) subjects for differences ⩾10/5 and ⩾20/10 mm Hg. Participants with higher home than ambulatory BP differences were older, had higher body mass index, higher office BP, more antihypertensive medication and lower glomerular filtration rate (P<0.01). Differences between home and ambulatory BP were highly reproducible (r=0.80 and 0.67 for systolic and diastolic BP, P<0.001). Both home and ambulatory BPs were associated with organ damage, but their difference was not. Many patients have a significantly higher home than ambulatory BP. Differences between home and ambulatory BP are reproducible, but not associated with hypertensive organ damage. Our findings suggest that ambulatory BP remains the standard of reference when positive differences between home and ambulatory BP exist.

Use of a 40-day rolling incidence to monitor pertussis in Nova Scotia, 2015.

BACKGROUND: Pertussis can cause a serious respiratory bacterial infection, especially in infants. Between January 1 and December 31, 2015, there was an increase in the number of reported pertussis cases in Nova Scotia (NS). Surveillance practices for pertussis in NS were challenging because immunization coverage data are not available and rate information was neither timely nor precise with respect to geography. Public health officials in NS decided to adopt a new surveillance technique to inform public health actions across the Province. OBJECTIVE: To assess the use of a 40-day rolling incidence rate to monitor pertussis activity in Nova Scotia. INTERVENTION: A 40-day rolling incidence rate was calculated for pertussis by age groups and various levels of geography. Public health authorities continued to anticipate new cases of pertussis if the contacts of known cases were still within the incubation period (range between six and 20 days). The 40-day incubation period was chosen to reflect twice the incubation period's upper range. Rates were calculated using Statistics Canada population projections for 2014 and then compared with traditional case counts and cumulative incidences. The usefulness of the statistics was assessed by public health decision makers. OUTCOMES: Increased pertussis activity was noted across NS, most notably in the South West region. The use of a 40-day rolling incidence rate as a surveillance tool provided more timely and geographically precise descriptions of ongoing trends in pertussis activity and helped to inform appropriate public health action. Health officials valued the information provided from the rolling incidence because it allowed them to manage activities based on weekly estimates at various levels of geography. CONCLUSION: Rolling incidence proved to be a useful tool to monitor a cyclical increase in pertussis cases in Nova Scotia and to inform related public health actions. The rolling incidence provided geographically precise and timely information that was useful to estimate new cases in the absence of reliable immunization coverage information. This method could supplement traditional epidemiological surveillance of future communicable disease events, especially those characterized by long incubation periods and low case counts.

Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency.

The prevalence of malignant hypertension has clearly fallen with the advent of anti-hypertensive medication but has remained stable over the past 30-40 years in spite of progress in diagnosis and management of hypertension. A diagnosis of malignant hypertension is usually based on the association of severely elevated blood pressure with a Keith and Wagener stage III or IV retinopathy. We believe that this definition can be reconsidered for several reasons. Although simple and pragmatic, this definition corresponds to a time when there were few techniques for assessment of hypertensive target organ involvement, and does not take into account involvement of kidney, brain and heart; whereas the overall prognosis largely depends on how much they are affected. On the contrary, the acute blood pressure level and especially diastolic should not be a hard diagnostic criterion as it does not itself constitute the prognosis of the condition. We propose to consider that malignant hypertension with retinopathy is only one of a number of possible presentation(s) of acute hypertension with multi organ damage (hypertension multi organ damage (MOD)) and that the recognition of these hypertensive emergencies, when retinopathy is lacking, be based on acute elevation of BP associated with impairment of at least three different target organs. The objective of a new and expanded definition is to facilitate recognition of these true emergencies. The condition is more common than usually perceived and would have a much worse prognosis than the usual forms of hypertension. Early recognition and management of hypertension-MOD are fundamental to any improvement in prognosis.

Arterial stiffness in periodontitis patients and controls. A case­control and pilot intervention study.

Increased arterial stiffness (AS) is an important indicator for atherosclerotic cardiovascular disease (ACVD). Epidemiologically, periodontitis and ACVD are associated. Therefore, we aimed to investigate AS in periodontitis patients and controls. In addition, we explored the effect of periodontal therapy on AS in a sub-group of cases. Pulse-wave velocity (PWV), a non-invasive chair-side function test for AS, was measured in periodontitis patients (n=57; mean age 46.6 years) and compared with a reference group (n=48; mean age 45.5 years). In addition, 45 cases (mean age 46.9 years) were 6 months followed after periodontal treatment, to explore a possible effect on arterial function. Periodontitis patients showed a significantly increased PWV compared with the reference group (8.01±0.20 vs. 7.36±0.22 m s(-1) respectively; P=0.029) and this remained significant after adjustments for ACVD risk factors (P=0.019). After periodontal therapy, no significant reduction in PWV was seen (8.00±1.8 to 7.82±1.6 m s(-1); P=0.13), but systolic blood pressure (SBP) was significantly reduced (119.8±14.6 to 116.9±15.1 mm Hg; P=0.040). It can be concluded that periodontitis is associated with increased AS. This confirms with a new parameter the association of periodontitis with ACVD. Although periodontal treatment did not lower AS significantly, a modest reduction of SBP after 6 months was observed.

Placental expression of heparan sulfate 3-O-sulfotransferase-3A1 in normotensive and pre-eclamptic pregnancies.

INTRODUCTION: The endothelial glycocalyx, consisting of membrane-bound proteoglycans and attached glycosaminoglycans plays an important role in vascular homeostasis. We aimed to assess whether glycocalyx mRNA transcripts are differentially expressed in placental tissue of pre-eclamptic and normotensive women. METHODS: We evaluated the expression of transcripts encoding for proteins involved in glycocalyx synthesis and degradation using a microarray analysis of placental mRNA obtained from pre-eclamptic and normotensive women. Participants were recruited from the department of obstetrics at a university hospital in Amsterdam, The Netherlands. The most prominent differentially expressed transcript was validated by qPCR on 112 additional placenta samples. RESULTS: Of 78 preselected genes involved in glycocalyx synthesis and degradation, only HS3ST3A1 mRNA was differentially expressed in placental tissue obtained from pre-eclamptic women (N = 12) compared to normotensive women (N = 12, fold change = 0.61, p = 0.02). Validation with qPCR in additional placental samples of 64 normotensive and 48 pre-eclamptic women confirmed that normalized mRNA expression of HS3ST3A1 was decreased by 27% (95% CI 14%-41%) in placental tissue obtained from pre-eclamptic compared to normotensive women (p < 0.001). HS3ST3A1 expression was positively correlated with neonatal birth weight in normotensive women (r = 0.35, p < 0.01) and inversely correlated with mean arterial pressure of women with pre-eclampsia (r = 0.32, p = 0.02). CONCLUSIONS: The mRNA expression of HS3ST3A1, which encodes for a 3-O sulfating enzyme of heparan sulfate (3-OST-3A1), is decreased in pre-eclamptic placental tissue. Expression of this glycocalyx synthesis transcript is correlated with maternal blood pressure and neonatal birth weight, suggesting a possible role in pre-eclampsia-associated placental dysfunction.

Are insulin analogues detemir or glulisine used preferentially in overweight/obese subjects? A German multicentre analysis of 38560 type 2 diabetic patients from the DPV registry.

OBJECTIVE: Several studies suggest benefits of insulin analogues detemir or glulisine in overweight and obese patients with type 2 diabetes. The present multicentre study therefore examines, whether these insulin analogues are used more frequently in patients with increased body mass index. METHODS: Data of 38 560 adult type 2 diabetic patients using insulin analogues, from 150 centres in Germany, registered in a standardized, prospective, computer-based documentation program (DPV), were included. Patients were classified into body mass index categories according to World Health Organization. Analysis was stratified by 3 time periods. To adjust for confounding effects, multivariable logistic regression models were created. RESULTS: Detemir was preferentially used in overweight (OR 1.36, 95%-CI 1.20-1.53) and obese patients (OR 2.06, 95%-CI 1.84-2.31) compared to normal-weight patients. These effects remained significant after adjusting for sex, age, new/old federal state of Germany, size of centre, treatment in university clinic and clinic/specialized private practice. Models were additionally adjusted for time period and interaction of BMI category with age or sex. For glulisine, a minor effect was present when comparing obese to normal-weight patients (OR 1.26, 95%-CI 1.06-1.50). After adjustment, this finding was no longer significant. Stratified by obesity grade, class III obese patients more frequently used detemir or glulisine compared to class I obese patients. Comparing time periods, odds ratios did not differ, neither for detemir nor for glulisine. CONCLUSION: Detemir is used more often in overweight and obese patients compared to normal-weight patients. For glulisine, the relationship is less pronounced.