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).

Arterial stiffness as a risk factor for cardiovascular events and all-cause mortality in people with Type 2 diabetes.

AIM: To quantify the risk of different non-invasive arterial stiffness measurements with macrovascular disease and all-cause mortality in high-risk people with Type 2 diabetes. METHODS: We conducted a prospective cohort study of 1910 people with Type 2 diabetes included in the Second Manifestations of ARTerial disease (SMART) study. Arterial stiffness was assessed by brachial artery pulse pressure, normal range (≥0.9) ankle-brachial index and carotid artery distension. Cox regression was used to evaluate the effects of arterial stiffness on risk of cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. RESULTS: A total of 380 new cardiovascular events and 436 deaths occurred during a median (interquartile range) follow-up of 7.5 (4.1-11.0) years. A 10-mmHg higher brachial pulse pressure was related to higher hazard of cardiovascular events (hazard ratio 1.09, 95% CI 1.02 to 1.16) and all-cause mortality (hazard ratio 1.10, 95% CI 1.03 to 1.16). A 0.1-point lower ankle-brachial index within the normal range was related to a higher hazard of cardiovascular events (hazard ratio 1.13, 95% CI 1.01 to 1.27) and all-cause mortality (hazard ratio 1.17, 95% CI 1.04 to 1.31). A one-unit (10-3 ×kPa-1 ) lower carotid artery distensibility coefficient was related to a higher hazard of vascular mortality (hazard ratio 1.04, 95% CI 1.00 to 1.09) and all-cause mortality (hazard ratio 1.04, 95% CI 1.00 to 1.07). CONCLUSION: Increased arterial stiffness, as measured by either increased pulse pressure, normal-range ankle-brachial index or carotid artery distensibility coefficient, is related to increased hazard of cardiovascular events and all-cause mortality in people with Type 2 diabetes.

Association between vascular health and ovarian ageing in type 1 diabetes mellitus.

STUDY QUESTION: Is vascular health associated with ovarian reserve status using type 1 diabetes mellitus (DM-1) as a model for vascular compromise? SUMMARY ANSWER: No conclusive evidence for an association between vascular health and ovarian ageing was found in women with DM-1. WHAT IS KNOWN ALREADY: The mechanism behind advanced ovarian ageing has not yet been elucidated. We hypothesize that vascular impairment precedes ovarian ageing. DM-1 is hallmarked by premature vascular complications that may consequently play a role in the rate of primordial follicle decline. STUDY DESIGN, SIZE, DURATION: A cross-sectional, patient-control study was performed in 150 premenopausal, regular cycling women with DM-1, as well as a reference population of 177 healthy, fertile women. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a single-study visit, an inventory of both ovarian reserve and vascular status was carried out in the DM-1 group. A transvaginal ultrasound to calculate the antral follicle count (AFC) and blood sampling for anti-Müllerian hormone (AMH), lipids, C-reactive protein and HbA1c measurements were performed. Furthermore, vascular screening including measurements of blood pressure, flow-mediated dilation, peripheral arterial tonometry, pulse wave velocity, pulse wave analysis and intima-media thickness was carried out. The relative decrease in serum AMH levels in women with DM-1 compared with healthy references was investigated. MAIN RESULTS AND THE ROLE OF CHANCE: Systolic blood pressure was negatively correlated with both serum AMH (P= 0.006) and AFC (P= 0.004) in the DM-1 group. A non-linear relationship between HDL-cholesterol and serum AMH was found (P= 0.0001). No associations were detected between other vascular risk factors or vascular function tests and serum AMH or AFC in women with DM-1. With regard to the comparison of AMH levels between women with and without DM-1, mean AMH levels were 2.5 ± 1.9 ng/ml and 3.0 ± 2.8 ng/ml, respectively. After adjustment for confounders the difference in AMH levels between both groups appeared non-significant (fold change: 0.92, 95% confidence interval: 0.68-1.23). LIMITATIONS, REASON FOR CAUTION: The use of different AMH assays and the cross-sectional design may limit the interpretation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The lack of evident association between vascular health and ovarian ageing may be the result of an insufficient vascular compromise in the relatively young, DM-1 group. STUDY FUNDING/COMPETING INTERESTS: No external funding was received for conducting or publishing this study. F.Y., W.S., A.F., F.L.J.V., M.J.C.E. and H.W.d.V. have nothing to disclose. F.J.M.B. has received fees and grant support from the following companies: Ferring, Gedeon Richter, Merck Serono, Medical Specialties Distributors and Roche. TRIAL REGISTRATION NUMBER: Not applicable.

Adipose Tissue Dysfunction: Clinical Relevance and Diagnostic Possibilities.

Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity of adipose tissue is an important determinant of adipose tissue dysfunction, it can be diagnosed in both obese and lean individuals. This implies that not only quantity of adipose tissue should be used as a measure for adipose tissue dysfunction. Instead, focus should be on measuring quality of adipose tissue, which can be done with diagnostic modalities ranging from anthropometric measurements to tissue biopsies and advanced imaging techniques. In daily clinical practice, high quantity of visceral adipose tissue (reflected in high waist circumference or adipose tissue imaging), insulin resistance, or presence of the metabolic syndrome are easy and low-cost diagnostic modalities to evaluate presence or absence of adipose tissue dysfunction.

Multifactorial Prevention of Cardiovascular Disease in Patients with Hypertension: the Cardiovascular Polypill.

Hypertension is a major, if not the most important, contributor to the disease burden and premature death globally which is largely related to cardiovascular disease. In both the primary and the secondary preventions of cardiovascular disease, blood pressure (BP) targets are often not achieved which is similar to achievement of cholesterol goals. Combining aspirin, cholesterol and blood pressure-lowering agents into a fixed-dose combination pill called the cardiovascular polypill has been proposed as complementary care in the prevention of cardiovascular diseases in both the primary and secondary preventions of cardiovascular disease. This review article focuses on the potential role of fixed-dose combination therapy in the treatment of hypertension, outlines the pros and cons of combination therapy and emphasizes the rationale for trialling their use. Current and planned future cardiovascular polypill trials are summarized, and the prerequisites for implementation of the polypill strategy are described.

Age at menopause in women with type 1 diabetes mellitus: the OVADIA study.

STUDY QUESTION: Is type 1 diabetes a determinant of advanced ovarian ageing, resulting in an early age at natural menopause? SUMMARY ANSWER: No clear evidence was provided that type 1 diabetes is a determinant of accelerated ovarian ageing resulting in an early menopause. WHAT IS KNOWN ALREADY: The association between type 1 diabetes and early menopause has been examined previously with inconsistent results. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was performed in 140 post-menopausal women with, and 5426 post-menopausal women without, diabetes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Both women with and without diabetes had experienced natural menopause. Study participants filled out a standardized questionnaire including report of their age at last menstrual period. Differences in menopausal age were analysed using linear regression analyses, with adjustment for possible confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age at natural menopause was 49.8 ± 4.7 years in women with type 1 diabetes and 49.8 ± 4.1 in women without diabetes. Linear regression analyses showed that type 1 diabetes was not associated with an earlier menopause compared with the reference group without diabetes, after adjustment for age, smoking history and parity (difference in age at menopause between women with type 1 diabetes and reference group 0.34 years, 95% confidence interval -0.34, 1.01). LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. We had no information regarding microvascular complications therefore a possible association between vascular health and menopausal age could not be investigated. WIDER IMPLICATIONS OF THE FINDINGS: It has been hypothesized that the possible mechanism behind an accelerated ovarian ageing process in type 1 diabetes is prolonged poor glycaemic control and subsequent effects on vascular health. The improved glycaemic control during the last decades may have prevented vascular damage from occurring to an extent that would affect organ function. Nevertheless, the present findings are reassuring for reproductive health prospects in women with type 1 diabetes.

The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension.

OBJECTIVES: Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. METHODS: Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. RESULTS: Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m(2); p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. CONCLUSION: The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. KEY POINTS: • Renal denervation significantly decreased ambulatory blood pressure. • Renal denervation did not change renal oxygenation as determined by BOLD-MRI. • Absence of a change in renal oxygenation might be explained by autoregulation.

Increased Intracranial Arterial Pulsatility and Microvascular Brain Damage in Pseudoxanthoma Elasticum.

BACKGROUND AND PURPOSE: Carotid siphon calcification might contribute to the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum through increased arterial flow pulsatility. This study aimed to compare intracranial artery flow pulsatility, brain volumes, and small-vessel disease markers between patients with pseudoxanthoma elasticum and controls and the association between arterial calcification and pulsatility in pseudoxanthoma elasticum. MATERIALS AND METHODS: Fifty patients with pseudoxanthoma elasticum and 40 age- and sex-matched controls underwent 3T MR imaging, including 2D phase-contrast acquisitions for flow pulsatility in the assessment of ICA and MCA and FLAIR acquisitions for brain volumes, white matter lesions, and infarctions. All patients with pseudoxanthoma elasticum underwent CT scanning to measure siphon calcification. Flow pulsatility (2D phase-contrast), brain volumes, white matter lesions, and infarctions (3D T1 and 3D T2 FLAIR) were compared between patients and controls. The association between siphon calcification and pulsatility in pseudoxanthoma elasticum was tested with linear regression models. RESULTS: Patients with pseudoxanthoma elasticum (mean age, 57 [SD, 12] years; 24 men) had significantly higher pulsatility indexes (1.05; range, 0.94-1.21 versus 0.94; range, 0.82-1.04; P = .02), lower mean GM volumes (597 [SD, 53] mL versus 632 [SD, 53] mL; P < .01), more white matter lesions (2.6; range, 0.5-7.5 versus 1.1; range, 0.5-2.4) mL; P = .05), and more lacunar infarctions (64 versus 8, P = .04) than controls (mean age, 58 [SD, 11] years; 20 men). Carotid siphon calcification was associated with higher pulsatility indexes in patients with pseudoxanthoma elasticum (ß = 0.10; 95% CI, 0.01-0.18). CONCLUSIONS: Patients with pseudoxanthoma elasticum have increased intracranial artery flow pulsatility and measures of small-vessel disease. Carotid siphon calcification might underlie the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum.

Prediction of cerebral hyperperfusion after carotid endarterectomy with transcranial Doppler.

OBJECTIVES: To determine the diagnostic value for predicting cerebral hyperperfusion syndrome (CHS) by adding a transcranial Doppler (TCD) measurement in the early postoperative phase after carotid endarterectomy (CEA). DESIGN: Patients who underwent carotid endarterectomy between January 2004 and August 2010 and in whom both intra- and postoperative TCD monitoring were performed were included. METHODS: In 184 CEA patients the mean velocity (V(mean)) preoperatively (V1), pre-clamping (V2), post-declamping (V3) and postoperatively (V4) was measured using TCD. The intra-operative V(mean) increase ((V3 - V2)/V2) was compared to the postoperative increase ((V4 - V1)/V1) in relation to CHS. CHS was diagnosed if the patient developed neurological complaints in the presence of a preoperative V(mean) increase >100%. RESULTS: Sixteen patients (9%) had an intra-operative V(mean) increase >100% and 22 patients (12%) a postoperative V(mean) increase of >100%. In 10 patients (5%) CHS was diagnosed; two of those had an intra-operative V(mean) increase of >100% and nine postoperative V(mean) increase >100%. This results in a positive predictive value of 13% for the intra-operative and 41% for the postoperative measurement. CONCLUSIONS: Besides the commonly used intra-operative TCD monitoring additional TCD measurement in the early postoperative phase is useful to more accurately predict CHS after CEA.

Treatment of arterial calcification in patients with chronic limb threatening ischemia with etidronate: protocol of an investigator-initiated multicenter, double blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Pathologic studies have shown that in patients with critical limb threatening ischaemia (CLTI) medial arterial calcifications are frequently found and may be responsible for aggravating the disease. These extensive calcifitcations are found not only in arteries of the leg but also in the coronary arteries and the aorta. The progression of these calcifications is fast and they stiffen the vessel wall and may thus increase the cardiovascular risk. Reduction of progression of calcification may not only reduce the burden of CLTI but may also reduce the high residual cardiovascular risk. Medial calcifications have been halted by etidronate in other trials. Its potential to reduce the burden from peripheral vascular disease in CLTI and residual cardiovascular risk remains to be established. METHODS: This is an investigator-initiated multicenter, double blind, placebo-controlled, randomized trial comparing the effects of etidronate versus placebo in patients with CLTI. Subjects will be randomized to either treatment with etidronate for 12 months (cyclical 20 mg/kg for 2 weeks on and 10 weeks off) orally or placebo for 12 months (in a similar routine). The primary endpoint is the change in arterial calcification as quantified by CT-scan. Secondary endpoints are the number of amputations above and below the ankle, mortality, number of vascular interventions and quality of life. DISCUSSION: Up to now, the inert end stage of vascular disease in patients with CLTI, has been considered calcification of vessel walls. We believe there is reason to reverse causation and hypothesize that calcification causes vascular disease. This reversal can be proven in a clinical trial if halting the calcification process improves the outcome of the patient. Therefore we use etidronate, a bisphosphate that has proven to stop the calcification in several rare monogenetic calcifying diseases. We aim to perform this mechanistic proof-of-concept study hopefully leading to a clinical outcome study later on.

Waist circumference and metabolic risk factors have separate and additive effects on the risk of future Type 2 diabetes in patients with vascular diseases. A cohort study.

AIMS: To assess the effect of various measures of adiposity and of metabolic risk factors, both separately and in combination, on the risk of future Type 2 diabetes in patients with manifest vascular diseases. METHODS: This was a prospective cohort study in 2924 patients (mean age 59 ± 12 years) with manifest atherosclerosis. Metabolic risk factors were defined according to National Cholesterol Education Program criteria for the metabolic syndrome. Incidence of Type 2 diabetes was assessed by questionnaire and subsequent verification. RESULTS: During a median follow-up of 4.9 years (range 3.0-7.6 years) there were 178 cases (6.1%) of incident Type 2 diabetes. An increase with 1 sd waist circumference showed a strong association with incident Type 2 diabetes in both men (hazard ratio 2.45, 95% CI 1.97-3.04) and women (hazard ratio 1.77, 95% CI 1.38-2.26). Compared with patients with normal (i.e. below the National Cholesterol Education Program criteria for abdominal adiposity) waist circumference and < 3 metabolic risk factors, both patients with normal waist circumference and ≥ 3 metabolic risk factors and patients with high (i.e. above the National Cholesterol Education Program criteria for abdominal adiposity) waist circumference and < 3 metabolic risk factors had an increased risk of Type 2 diabetes (hazard ratio 2.44, 95% CI 1.37-4.36 and hazard ratio 3.61, 95% CI 2.23-5.85, respectively). Patients with both high waist circumference and ≥ 3 metabolic risk factors had the highest risk of developing Type 2 diabetes (hazard ratio 10.76, 95% CI 6.95-16.64). CONCLUSIONS: In patients with manifest atherosclerosis, both presence of ≥ 3 metabolic risk factors and presence of a high waist circumference alone are associated with increased risk for developing Type 2 diabetes. The combined presence of ≥ 3 metabolic risk factors and high waist circumference, which is present in 15% of patients, is associated with a 10-fold increased risk of future Type 2 diabetes. To identify patients with manifest atherosclerosis at the highest risk of developing Type 2 diabetes, fat distribution in combination with metabolic risk factors should be considered.

Pulsatility Attenuation along the Carotid Siphon in Pseudoxanthoma Elasticum.

We compared velocity pulsatility, distensibility, and pulsatility attenuation along the intracranial ICA and MCA between 50 patients with pseudoxanthoma elasticum and 40 controls. Patients with pseudoxanthoma elasticum had higher pulsatility and lower distensibility at all measured locations, except for a similar distensibility at C4. The pulsatility attenuation over the siphon was similar between patients with pseudoxanthoma elasticum and controls. This finding suggests that other disease mechanisms are the main contributors to increased intracranial pulsatility in pseudoxanthoma elasticum.

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.

Screening of cardiovascular agents in plasma with LC-MS/MS: A valuable tool for objective drug adherence assessment.

Adherence to cardiovascular preventive agents is important to prevent short and long term cardiovascular events. Recently, qualitatively compound screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has gained interest for drug adherence assessment in patients at high risk of cardiovascular events. Therefore, we developed and tested an assay including 52 compounds and metabolites, covering over 95% of the antihypertensive and antithrombotic agents available worldwide. Trichloroacetic acid was used as simple and fast method for protein precipitation. The assay was validated for lower limit of quantification (LLOQ), linearity, stability for freeze/thaw, room temperature, autosampler and matrix effects. The LLOQ for each compound was targeted under the population trough concentration (PTC) as reported in literature to assure high sensitivity for adherence detection. This was accomplished for 50 of 52 compounds with a LLOQ equal or lower compared to the PTC. Linearity was confirmed for all compounds (r2 > 0.995), except for acetylsalicylic acid (r2 = 0.991). For room temperature stability, 12 compounds showed degradation over 20% after 20 h. 3 compounds suffer from matrix effect with recoveries < 50%. After analytical validation, blood samples from 91 patients with difficult-to-treat hypertension were analyzed. Patients were unaware of adherence assessment. Adherence varied largely per agent and per concentration ratio (CR) (ratio of the detected concentration with LC-MS/MS and the PTC) cut-off value. Additionally, stratification by adherence group showed that the percentage of patients classified as non-adherent increased from 6.6% for qualitative analysis (pos/neg) to 19.8% for a CR cut-off of 0.5. The data imply that using the CR cut off values has a significant and relevant effect on patient adherence classification.

Elastic compression stockings one year after DVT diagnosis: Who might discontinue?

BACKGROUND: Elastic compression stockings (ECS) are uncomfortable to wear but may prevent post-thrombotic syndrome (PTS). The ability to predict PTS may help clinical decision making regarding the optimal duration of ECS after deep vein thrombosis (DVT). AIMS: Predefined endpoint analysis of the Octavia study that randomized patients who compliantly used ECS up to one year after DVT to continue or discontinue ECS treatment. Primary aim was to identify predictors of PTS. METHODS: Patient characteristics were collected and ultrasonography was performed to assess reflux, residual thrombosis and persistent thrombus load 12 months after DVT. Multivariable analyses were performed to identify factors related to PTS. RESULTS: Thrombus score ≥ 3, BMI ≥ 26, duration of symptoms before DVT diagnosis ≥ 8 days and a Villalta score of 2-4 points were statistically significant predictors of PTS. The predictive value for PTS for the assessed variables was not different between the 2 treatment groups. In the stop ECS group, 3.2% (95%CI 0.08-18) of patients without any predictors for PTS were diagnosed with mild PTS during follow-up, and none with severe PTS, for a sensitivity of 98% (95% CI 89-100), a specificity of 14% (95% CI 10-20), a positive predictive value of 20% (95% CI 19-22), and a negative predictive value of 97% (95% CI 81-100). CONCLUSION: We identified 4 predictors of PTS occurring in the 2nd year after DVT. Our findings may be used to decide on whether to continue ECS treatment for an additional year, after one year of compliant ECS use, keeping in mind that patients with none of the predictors will have the lowest PTS incidence.

Cardiovascular events and all-cause mortality by albuminuria and decreased glomerular filtration rate in patients with vascular disease.

OBJECTIVES: Albuminuria and decreased estimated glomerular filtration rate (eGFR) are associated with increased cardiovascular risk, but do not necessarily coexist and have different pathophysiological mechanisms. This study aims to evaluate separate and combined effects of decreased eGFR and albuminuria on the occurrence of vascular diseases and mortality in patients with vascular disease. DESIGN: Prospective cohort study. SETTING: University Medical Center Utrecht, the Netherlands. SUBJECTS AND MAIN OUTCOME MEASURES: 2600 patients with vascular disease were followed for vascular events, vascular and all-cause mortality. Cox regression analysis was used to calculate hazard ratios (HRs) according to eGFR (MDRD) and albuminuria (albumin-to-creatinine ratio >3 mg mmol(-1)). RESULTS: In this population, 14.0% had albuminuria, 15.6% had eGFR <60 ml min(-1) 1.73 m(-2) and 5.2% had both. Nonalbuminuric decreased eGFR and albuminuria with normal eGFR generated moderately increased risks on all outcomes. eGFR <60 ml min(-1) 1.73 m(-2) without albuminuria mainly influenced the risk of vascular events (HR 1.50; 1.05-2.15) whilst albuminuria with eGFR >or=60 ml min(-1) 1.73 m(-2) principally affected all-cause mortality (HR 1.53; 1.04-2.26). The combination of eGFR <60 ml min(-1) 1.73 m(-2) and albuminuria was associated with an increased risk for vascular events (HR 2.27; 1.54-3.34), vascular mortality (HR 2.22; 1.40-3.52) and all-cause mortality (HR 1.84; 1.25-2.69). Comparable results were found in additional analyses amongst 759 diabetic patients. CONCLUSIONS: The combination of decreased eGFR with albuminuria is associated with the highest risks of vascular events, vascular and all-cause mortality in patients with vascular diseases. To adequately estimate vascular risk associated with impaired renal function, both eGFR and urinary albumin should be considered.

Effect of metabolic syndrome or type II diabetes mellitus on the occurrence of recurrent vascular events in hypertensive patients.

Patients with hypertension and manifest vascular disease are at high risk for recurrent cardiovascular diseases. It is unknown if the metabolic syndrome further increases the risk in these patients. This study aims to quantify the effect of metabolic syndrome and type II diabetes on cardiovascular events in hypertensive patients with vascular disease. A total of 2,196 hypertensive patients with vascular disease (cerebrovascular disease (34%), coronary heart disease (50%), peripheral arterial disease (28%), abdominal aortic aneurysm (13%)) from the Second Manifestations of Arterial Disease study were followed for up to 10 years (mean 3.9 years) for death, stroke and myocardial infarction. Age and sex adjusted hazard ratios (HR) were calculated for hypertensive patients with metabolic syndrome but without diabetes (n=775) and for hypertensive patients with type II diabetes (n=381), compared to merely hypertensive patients (n=1,040). Forty-nine percent had metabolic syndrome (NCEP ATPIII definition) and 17% had type II diabetes. Metabolic syndrome predicted vascular death (HR 1.41, 95% confidence interval (CI) 1.01-1.98), stroke (HR 1.36, 95% CI 0.85-2.16) and myocardial infarction (HR 1.40, 95% CI 0.97-2.01). Type II diabetes accounted for even higher risks of vascular end points (HR 1.41-1.64). The effect of metabolic syndrome on future events could not be explained by the presence of type II diabetes. Even in high-risk patients with hypertension and vascular disease, presence of metabolic syndrome or type II diabetes identifies patients at high risk for future cardiovascular events. Identifying metabolic syndrome patients may direct therapy focusing on treatment of insulin resistance by reducing weight and increasing physical activity.

Hepatosplenic gammadelta T-cell lymphoma: A case report.

A 53-year-old man complained of weight loss, night sweats, and splenomegaly. The patient was diagnosed with stage IV hepatosplenic gammadelta T-cell non-Hodgkin's lymphoma, a highly aggressive and rare form of peripheral T-cell lymphoma. After completing CHOP chemotherapy, the patient relapsed. He did not respond to subsequent alemtuzumab therapy.

[Infection-induced vascular disease: little evidence according to the Koch's postulates]. / Infectie als oorzaak van vaatziekten: weinig evidence volgens de postulaten van Koch.

Infections with Cytomegalovirus, influenza virus, HIV and Chlamydophila pneumoniae may contribute to the development of vascular disease by infecting the vascular wall directly or by initiating and propagating low-grade chronic inflammation. Although this association appears plausible, it hardly fulfils Koch's postulates. Based on the results of large randomised trials, it appears that antibiotic treatment targeting C. pneumoniae does not reduce the incidence of new vascular events in patients with clinically manifest vascular disease. Influenza vaccination reduces the incidence of vascular disorders. Therefore efforts to optimise participation of high-risk patients in the influenza vaccination programme are advisable.