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Item does not contain fulltext, OBJECTIVES: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics. DESIGN: Individual patient level data meta-analysis and modelling study. SETTING: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies. PARTICIPANTS: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated. MAIN OUTCOME MEASURE: Adjudicated diagnosis of acute heart failure. RESULTS: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across al

Item does not contain fulltext, BACKGROUND: The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS: In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS: We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3.0 [IQR 1.0-5.0] vs 3.0 [1.1-5.9], p=0.52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0.87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0.82). On secondary endpoints we found no differences in health-r

Item does not contain fulltext, BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapyresistant 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.

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (–1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514

Item does not contain fulltext, BACKGROUND: The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS: In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS: We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3.0 [IQR 1.0-5.0] vs 3.0 [1.1-5.9], p=0.52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0.87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0.82). On secondary endpoints we found no differences in health-r

Item does not contain fulltext, BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapyresistant 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.

Item does not contain fulltext, BACKGROUND: The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS: In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS: We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3.0 [IQR 1.0-5.0] vs 3.0 [1.1-5.9], p=0.52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0.87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0.82). On secondary endpoints we found no differences in health-r

Item does not contain fulltext, Primary aldosteronism (PA) is characterized by autonomic aldosterone production, usually leading to severe hypertension and hypokalaemia. - PA is a heterogeneous condition caused by sporadic adrenal adenoma, bilateral adrenal hyperplasia or rare familial forms.- Familial aldosteronism type 1 is caused by a hybrid gene that codes for an ACTH-sensitive form of aldosterone synthase.- Familial aldosteronism type 3 was recently recognized as a new form of PA caused by mutation in KCNJ5. The clinical manifestations vary from life-threatening PA and pronounced adrenal hyperplasia to milder forms.- In addition to germline mutations in KCNJ5, somatic KCNJ5 mutations are present in about 40% of aldosterone-producing adrenal adenomas. Mutations in three other genes are also regularly observed.- All these mutations cause increased aldosterone synthase activity, eventually leading to PA.- In patients under 20 with PA, familial forms must be excluded before proceeding to adrenalectomy.

Item does not contain fulltext, Primary aldosteronism (PA) is characterized by autonomic aldosterone production, usually leading to severe hypertension and hypokalaemia. - PA is a heterogeneous condition caused by sporadic adrenal adenoma, bilateral adrenal hyperplasia or rare familial forms.- Familial aldosteronism type 1 is caused by a hybrid gene that codes for an ACTH-sensitive form of aldosterone synthase.- Familial aldosteronism type 3 was recently recognized as a new form of PA caused by mutation in KCNJ5. The clinical manifestations vary from life-threatening PA and pronounced adrenal hyperplasia to milder forms.- In addition to germline mutations in KCNJ5, somatic KCNJ5 mutations are present in about 40% of aldosterone-producing adrenal adenomas. Mutations in three other genes are also regularly observed.- All these mutations cause increased aldosterone synthase activity, eventually leading to PA.- In patients under 20 with PA, familial forms must be excluded before proceeding to adrenalectomy.

Item does not contain fulltext, BACKGROUND: The aldosterone-to-renin ratio (ARR) is a widely used screening test for primary aldosteronism. Current guidelines recommend a cut-off value of 91 pmol/mU. Studies on its sensitivity, specificity, reproducibility and the role of medication have been conflicting. We prospectively assessed the test characteristics of the ARR and the effect of combination antihypertensive treatment. METHODS: In 178 patients with persistent hypertension despite the use of at least two antihypertensives, plasma renin and aldosterone were assessed twice within an interval of 4 weeks. All patients underwent an intravenous salt loading test. A posttest plasma aldosterone exceeding 235 pmol/l was considered diagnostic for primary aldosteronism. ARR was repeated after 4 weeks of standardized treatment with a calcium channel blocker and/or alpha-adrenergic-receptor blocker. RESULTS: The prevalence of primary aldosteronism was 15.2%. The median ARR was 35.0 (interquartile range 16.2-82.0) in primary aldosteronism versus 7.1 (2.2-17.5) pmol/mU in essential hypertensive patients (P < 0.001). Under random medication, the ARR had 22.2% sensitivity and 98.7% specificity. On standardized treatment, the ARR rose from 9.6 (2.5-24.8) to 21.4 (10.8-52.1) (P < 0.001). Multivariate regression showed that angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II-receptor blockers were responsible for the lower ARR during random treatment. The area under the receiver operating characteristic curve was, however, similar under random and standardized treatment (84 vs. 86%, respectively, P = 0.314). Bland-Altman plots showed an almost five-fold difference in ARR values taken under the same conditions. CONCLUSION: ARR sensitivity for primary aldosteronism is low when the recommended cut-off is used. Reproducibility is also poor, stressing the need for alternative screening tests.

Item does not contain fulltext, OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone. RESULTS: Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction. CONCLUSIONS: The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.

Item does not contain fulltext, OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone. RESULTS: Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction. CONCLUSIONS: The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.

Item does not contain fulltext, BACKGROUND: The aldosterone-to-renin ratio (ARR) is a widely used screening test for primary aldosteronism. Current guidelines recommend a cut-off value of 91 pmol/mU. Studies on its sensitivity, specificity, reproducibility and the role of medication have been conflicting. We prospectively assessed the test characteristics of the ARR and the effect of combination antihypertensive treatment. METHODS: In 178 patients with persistent hypertension despite the use of at least two antihypertensives, plasma renin and aldosterone were assessed twice within an interval of 4 weeks. All patients underwent an intravenous salt loading test. A posttest plasma aldosterone exceeding 235 pmol/l was considered diagnostic for primary aldosteronism. ARR was repeated after 4 weeks of standardized treatment with a calcium channel blocker and/or alpha-adrenergic-receptor blocker. RESULTS: The prevalence of primary aldosteronism was 15.2%. The median ARR was 35.0 (interquartile range 16.2-82.0) in primary aldosteronism versus 7.1 (2.2-17.5) pmol/mU in essential hypertensive patients (P < 0.001). Under random medication, the ARR had 22.2% sensitivity and 98.7% specificity. On standardized treatment, the ARR rose from 9.6 (2.5-24.8) to 21.4 (10.8-52.1) (P < 0.001). Multivariate regression showed that angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II-receptor blockers were responsible for the lower ARR during random treatment. The area under the receiver operating characteristic curve was, however, similar under random and standardized treatment (84 vs. 86%, respectively, P = 0.314). Bland-Altman plots showed an almost five-fold difference in ARR values taken under the same conditions. CONCLUSION: ARR sensitivity for primary aldosteronism is low when the recommended cut-off is used. Reproducibility is also poor, stressing the need for alternative screening tests.

Item does not contain fulltext, OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone. RESULTS: Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction. CONCLUSIONS: The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.

Item does not contain fulltext, BACKGROUND: The aldosterone-to-renin ratio (ARR) is a widely used screening test for primary aldosteronism. Current guidelines recommend a cut-off value of 91 pmol/mU. Studies on its sensitivity, specificity, reproducibility and the role of medication have been conflicting. We prospectively assessed the test characteristics of the ARR and the effect of combination antihypertensive treatment. METHODS: In 178 patients with persistent hypertension despite the use of at least two antihypertensives, plasma renin and aldosterone were assessed twice within an interval of 4 weeks. All patients underwent an intravenous salt loading test. A posttest plasma aldosterone exceeding 235 pmol/l was considered diagnostic for primary aldosteronism. ARR was repeated after 4 weeks of standardized treatment with a calcium channel blocker and/or alpha-adrenergic-receptor blocker. RESULTS: The prevalence of primary aldosteronism was 15.2%. The median ARR was 35.0 (interquartile range 16.2-82.0) in primary aldosteronism versus 7.1 (2.2-17.5) pmol/mU in essential hypertensive patients (P < 0.001). Under random medication, the ARR had 22.2% sensitivity and 98.7% specificity. On standardized treatment, the ARR rose from 9.6 (2.5-24.8) to 21.4 (10.8-52.1) (P < 0.001). Multivariate regression showed that angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II-receptor blockers were responsible for the lower ARR during random treatment. The area under the receiver operating characteristic curve was, however, similar under random and standardized treatment (84 vs. 86%, respectively, P = 0.314). Bland-Altman plots showed an almost five-fold difference in ARR values taken under the same conditions. CONCLUSION: ARR sensitivity for primary aldosteronism is low when the recommended cut-off is used. Reproducibility is also poor, stressing the need for alternative screening tests.

Item does not contain fulltext, BACKGROUND: Add-on therapy with aldosterone receptor antagonists has been reported to lower blood pressure (BP) in patients with uncontrolled hypertension. We assessed potential predictors of this response. METHODS: In essential hypertensive patients with uncontrolled BP, despite the use of at least two antihypertensives, plasma renin and aldosterone concentrations and the transtubular potassium gradient (TTKG) were measured. Patients were treated with eplerenone 50 mg daily on top of their own medication. The office and ambulatory BP response and biochemical changes were evaluated after 1 week and 3 months of treatment and 6 weeks after discontinuation. Potential predictors for the change in 24-h ambulatory BP were tested in a multivariate regression model. RESULTS: One hundred and seventeen patients with a mean age of 50.5 +/- 6.6 years were included. Office BP decreased from 149/91 to 142/87 mmHg (P < 0.001) and ambulatory BP from 141/87 to 132/83 mmHg after 3 months of treatment (P < 0.001). Six weeks after discontinuation of eplerenone, office and ambulatory BP measurements returned to baseline values. Treatment resulted in a small rise in serum potassium and creatinine, and a small decrease in the TTKG. In a multivariate model, neither renin, aldosterone, or their ratio, nor the TTKG predicted the BP response. Only baseline ambulatory SBP predicted the BP response, whereas the presence of left ventricular hypertrophy was associated with a smaller BP reduction. CONCLUSION: Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension. This effect is unrelated to circulating renin-angiotensin-aldosterone system activity and renal mineralocorticoid receptor activity as assessed by the TTKG.

Item does not contain fulltext, BACKGROUND: Add-on therapy with aldosterone receptor antagonists has been reported to lower blood pressure (BP) in patients with uncontrolled hypertension. We assessed potential predictors of this response. METHODS: In essential hypertensive patients with uncontrolled BP, despite the use of at least two antihypertensives, plasma renin and aldosterone concentrations and the transtubular potassium gradient (TTKG) were measured. Patients were treated with eplerenone 50 mg daily on top of their own medication. The office and ambulatory BP response and biochemical changes were evaluated after 1 week and 3 months of treatment and 6 weeks after discontinuation. Potential predictors for the change in 24-h ambulatory BP were tested in a multivariate regression model. RESULTS: One hundred and seventeen patients with a mean age of 50.5 +/- 6.6 years were included. Office BP decreased from 149/91 to 142/87 mmHg (P < 0.001) and ambulatory BP from 141/87 to 132/83 mmHg after 3 months of treatment (P < 0.001). Six weeks after discontinuation of eplerenone, office and ambulatory BP measurements returned to baseline values. Treatment resulted in a small rise in serum potassium and creatinine, and a small decrease in the TTKG. In a multivariate model, neither renin, aldosterone, or their ratio, nor the TTKG predicted the BP response. Only baseline ambulatory SBP predicted the BP response, whereas the presence of left ventricular hypertrophy was associated with a smaller BP reduction. CONCLUSION: Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension. This effect is unrelated to circulating renin-angiotensin-aldosterone system activity and renal mineralocorticoid receptor activity as assessed by the TTKG.

Item does not contain fulltext, BACKGROUND: Add-on therapy with aldosterone receptor antagonists has been reported to lower blood pressure (BP) in patients with uncontrolled hypertension. We assessed potential predictors of this response. METHODS: In essential hypertensive patients with uncontrolled BP, despite the use of at least two antihypertensives, plasma renin and aldosterone concentrations and the transtubular potassium gradient (TTKG) were measured. Patients were treated with eplerenone 50 mg daily on top of their own medication. The office and ambulatory BP response and biochemical changes were evaluated after 1 week and 3 months of treatment and 6 weeks after discontinuation. Potential predictors for the change in 24-h ambulatory BP were tested in a multivariate regression model. RESULTS: One hundred and seventeen patients with a mean age of 50.5 +/- 6.6 years were included. Office BP decreased from 149/91 to 142/87 mmHg (P < 0.001) and ambulatory BP from 141/87 to 132/83 mmHg after 3 months of treatment (P < 0.001). Six weeks after discontinuation of eplerenone, office and ambulatory BP measurements returned to baseline values. Treatment resulted in a small rise in serum potassium and creatinine, and a small decrease in the TTKG. In a multivariate model, neither renin, aldosterone, or their ratio, nor the TTKG predicted the BP response. Only baseline ambulatory SBP predicted the BP response, whereas the presence of left ventricular hypertrophy was associated with a smaller BP reduction. CONCLUSION: Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension. This effect is unrelated to circulating renin-angiotensin-aldosterone system activity and renal mineralocorticoid receptor activity as assessed by the TTKG.

Item does not contain fulltext, OBJECTIVES: The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations. BACKGROUND: AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. METHODS: AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies. RESULTS: We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 +/- 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 +/- 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 +/- 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005). CONCLUSIONS: AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.

Item does not contain fulltext, BACKGROUND: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear. OBJECTIVE: To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions. DESIGN: Prospective population-based study. SETTING: The Rotterdam Study, Rotterdam, the Netherlands. PARTICIPANTS: 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]). MEASUREMENTS: Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity). RESULTS: Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal. LIMITATION: The findings may not be generalizable to younger or nonwhite populations. CONCLUSION: Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score scree

1 februari 2012, Item does not contain fulltext, BACKGROUND: Aortic augmentation index (AIx) but not carotid-femoral pulse wave velocity (cfPWV) has reported to decrease in response to vasodilators, which has been related to changes in the timing and/or intensity of wave reflection. Yet, recent evidence indicates that arterial reservoir pressure rather than wave reflection is the most important determinant of AIx. METHODS: Using radial artery applanation tonometry and a general transfer function AIx, aortic pulse wave reflection time and cfPWV (foot-to-foot method) were determined in 10 patients with severe autonomic failure and in 14 healthy individuals during supine rest and graded head-up tilting. RESULTS: During supine rest, mean blood pressure (BP) (127.6 +/- 21.5 and 97.5 +/- 9.4 mmHg), AIx (32.4 +/- 13.0 and 23.1 +/- 8.7%) and cfPWV (12.1 +/- 3.6 and 8.9 +/- 1.6 m/s) were higher in patients than in controls. In patients, BP decreased by 18.7 +/- 9.8 and 39.6 +/- 11.7%, AIx by 39.2 +/- 27.5 and 100.9 +/- 78.1% and cfPWV by 12.0 +/- 10.5 and 27.7 +/- 13.5% in response to 30 and 60 degrees head-up tilting. Decreases in AIx and cfPWV correlated with the BP fall (r = 0.67, P = 0.001 and r = 0.75, P < 0.001), but changes in AIx and cfPWV were unrelated. In controls, AIx during head-up tilting decreased despite increases in vascular tone and cfPWV. Aortic reflection time in patients and controls during tilting did not change. Stepwise regression analysis revealed that 68% of the variation in AIx could be explained by the BP fall and reflection time and 76% of the variation in cfPWV by the BP fall and sex. CONCLUSION: In a clinical model of autonomic failure, both AIx and cfPWV largely depend on instantaneous BP, but these two variables are unrelated, supporting the contention that aortic reservoir pressure rather than wave reflection is the main determinant of AIx.

Item does not contain fulltext, OBJECTIVES: The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations. BACKGROUND: AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. METHODS: AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies. RESULTS: We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 +/- 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 +/- 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 +/- 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005). CONCLUSIONS: AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.

Item does not contain fulltext, BACKGROUND: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear. OBJECTIVE: To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions. DESIGN: Prospective population-based study. SETTING: The Rotterdam Study, Rotterdam, the Netherlands. PARTICIPANTS: 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]). MEASUREMENTS: Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity). RESULTS: Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal. LIMITATION: The findings may not be generalizable to younger or nonwhite populations. CONCLUSION: Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score scree

01 februari 2012, Item does not contain fulltext, BACKGROUND: Aortic augmentation index (AIx) but not carotid-femoral pulse wave velocity (cfPWV) has reported to decrease in response to vasodilators, which has been related to changes in the timing and/or intensity of wave reflection. Yet, recent evidence indicates that arterial reservoir pressure rather than wave reflection is the most important determinant of AIx. METHODS: Using radial artery applanation tonometry and a general transfer function AIx, aortic pulse wave reflection time and cfPWV (foot-to-foot method) were determined in 10 patients with severe autonomic failure and in 14 healthy individuals during supine rest and graded head-up tilting. RESULTS: During supine rest, mean blood pressure (BP) (127.6 +/- 21.5 and 97.5 +/- 9.4 mmHg), AIx (32.4 +/- 13.0 and 23.1 +/- 8.7%) and cfPWV (12.1 +/- 3.6 and 8.9 +/- 1.6 m/s) were higher in patients than in controls. In patients, BP decreased by 18.7 +/- 9.8 and 39.6 +/- 11.7%, AIx by 39.2 +/- 27.5 and 100.9 +/- 78.1% and cfPWV by 12.0 +/- 10.5 and 27.7 +/- 13.5% in response to 30 and 60 degrees head-up tilting. Decreases in AIx and cfPWV correlated with the BP fall (r = 0.67, P = 0.001 and r = 0.75, P < 0.001), but changes in AIx and cfPWV were unrelated. In controls, AIx during head-up tilting decreased despite increases in vascular tone and cfPWV. Aortic reflection time in patients and controls during tilting did not change. Stepwise regression analysis revealed that 68% of the variation in AIx could be explained by the BP fall and reflection time and 76% of the variation in cfPWV by the BP fall and sex. CONCLUSION: In a clinical model of autonomic failure, both AIx and cfPWV largely depend on instantaneous BP, but these two variables are unrelated, supporting the contention that aortic reservoir pressure rather than wave reflection is the main determinant of AIx.

01 februari 2012, Item does not contain fulltext, BACKGROUND: Aortic augmentation index (AIx) but not carotid-femoral pulse wave velocity (cfPWV) has reported to decrease in response to vasodilators, which has been related to changes in the timing and/or intensity of wave reflection. Yet, recent evidence indicates that arterial reservoir pressure rather than wave reflection is the most important determinant of AIx. METHODS: Using radial artery applanation tonometry and a general transfer function AIx, aortic pulse wave reflection time and cfPWV (foot-to-foot method) were determined in 10 patients with severe autonomic failure and in 14 healthy individuals during supine rest and graded head-up tilting. RESULTS: During supine rest, mean blood pressure (BP) (127.6 +/- 21.5 and 97.5 +/- 9.4 mmHg), AIx (32.4 +/- 13.0 and 23.1 +/- 8.7%) and cfPWV (12.1 +/- 3.6 and 8.9 +/- 1.6 m/s) were higher in patients than in controls. In patients, BP decreased by 18.7 +/- 9.8 and 39.6 +/- 11.7%, AIx by 39.2 +/- 27.5 and 100.9 +/- 78.1% and cfPWV by 12.0 +/- 10.5 and 27.7 +/- 13.5% in response to 30 and 60 degrees head-up tilting. Decreases in AIx and cfPWV correlated with the BP fall (r = 0.67, P = 0.001 and r = 0.75, P < 0.001), but changes in AIx and cfPWV were unrelated. In controls, AIx during head-up tilting decreased despite increases in vascular tone and cfPWV. Aortic reflection time in patients and controls during tilting did not change. Stepwise regression analysis revealed that 68% of the variation in AIx could be explained by the BP fall and reflection time and 76% of the variation in cfPWV by the BP fall and sex. CONCLUSION: In a clinical model of autonomic failure, both AIx and cfPWV largely depend on instantaneous BP, but these two variables are unrelated, supporting the contention that aortic reservoir pressure rather than wave reflection is the main determinant of AIx.

Item does not contain fulltext, BACKGROUND: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear. OBJECTIVE: To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions. DESIGN: Prospective population-based study. SETTING: The Rotterdam Study, Rotterdam, the Netherlands. PARTICIPANTS: 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]). MEASUREMENTS: Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity). RESULTS: Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal. LIMITATION: The findings may not be generalizable to younger or nonwhite populations. CONCLUSION: Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score scree

Item does not contain fulltext, OBJECTIVES: The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations. BACKGROUND: AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. METHODS: AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies. RESULTS: We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 +/- 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 +/- 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 +/- 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005). CONCLUSIONS: AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.

Contains fulltext : 81485.pdf (publisher's version ) (Closed access), BACKGROUND: Little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) and impaired renal function. OBJECTIVE: To determine the efficacy and safety of stent placement in patients with ARAS and impaired renal function. DESIGN: Randomized clinical trial. Randomization was centralized and computer generated, and allocation was assigned by e-mail. Patients, providers, and persons who assessed outcomes were not blinded to treatment assignment. SETTING: 10 European medical centers. PARTICIPANTS: 140 patients with creatinine clearance less than 80 mL/min per 1.73 m(2) and ARAS of 50% or greater. INTERVENTION: Stent placement and medical treatment (64 patients) or medical treatment only (76 patients). Medical treatment consisted of antihypertensive treatment, a statin, and aspirin. MEASUREMENTS: The primary end point was a 20% or greater decrease in creatinine clearance. Secondary end points included safety and cardiovascular morbidity and mortality. RESULTS: Forty-six of 64 patients assigned to stent placement had the procedure. Ten of the 64 patients (16%) in the stent placement group and 16 patients (22%) in the medication group reached the primary end point (hazard ratio, 0.73 [95% CI, 0.33 to 1.61]). Serious complications occurred in the stent group, including 2 procedure-related deaths (3%), 1 late death secondary to an infected hematoma, and 1 patient who required dialysis secondary to cholesterol embolism. The groups did not differ for other secondary end points. LIMITATION: Many patients were falsely identified as having renal artery stenosis greater than 50% by noninvasive imaging and did not ultimately require stenting. CONCLUSION: Stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications. The study findings favor a conservative approach to patients with ARAS, focused on cardi

Contains fulltext : 81485.pdf (publisher's version ) (Closed access), BACKGROUND: Little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) and impaired renal function. OBJECTIVE: To determine the efficacy and safety of stent placement in patients with ARAS and impaired renal function. DESIGN: Randomized clinical trial. Randomization was centralized and computer generated, and allocation was assigned by e-mail. Patients, providers, and persons who assessed outcomes were not blinded to treatment assignment. SETTING: 10 European medical centers. PARTICIPANTS: 140 patients with creatinine clearance less than 80 mL/min per 1.73 m(2) and ARAS of 50% or greater. INTERVENTION: Stent placement and medical treatment (64 patients) or medical treatment only (76 patients). Medical treatment consisted of antihypertensive treatment, a statin, and aspirin. MEASUREMENTS: The primary end point was a 20% or greater decrease in creatinine clearance. Secondary end points included safety and cardiovascular morbidity and mortality. RESULTS: Forty-six of 64 patients assigned to stent placement had the procedure. Ten of the 64 patients (16%) in the stent placement group and 16 patients (22%) in the medication group reached the primary end point (hazard ratio, 0.73 [95% CI, 0.33 to 1.61]). Serious complications occurred in the stent group, including 2 procedure-related deaths (3%), 1 late death secondary to an infected hematoma, and 1 patient who required dialysis secondary to cholesterol embolism. The groups did not differ for other secondary end points. LIMITATION: Many patients were falsely identified as having renal artery stenosis greater than 50% by noninvasive imaging and did not ultimately require stenting. CONCLUSION: Stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications. The study findings favor a conservative approach to patients with ARAS, focused on cardi

Contains fulltext : 81485.pdf (publisher's version ) (Closed access), BACKGROUND: Little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) and impaired renal function. OBJECTIVE: To determine the efficacy and safety of stent placement in patients with ARAS and impaired renal function. DESIGN: Randomized clinical trial. Randomization was centralized and computer generated, and allocation was assigned by e-mail. Patients, providers, and persons who assessed outcomes were not blinded to treatment assignment. SETTING: 10 European medical centers. PARTICIPANTS: 140 patients with creatinine clearance less than 80 mL/min per 1.73 m(2) and ARAS of 50% or greater. INTERVENTION: Stent placement and medical treatment (64 patients) or medical treatment only (76 patients). Medical treatment consisted of antihypertensive treatment, a statin, and aspirin. MEASUREMENTS: The primary end point was a 20% or greater decrease in creatinine clearance. Secondary end points included safety and cardiovascular morbidity and mortality. RESULTS: Forty-six of 64 patients assigned to stent placement had the procedure. Ten of the 64 patients (16%) in the stent placement group and 16 patients (22%) in the medication group reached the primary end point (hazard ratio, 0.73 [95% CI, 0.33 to 1.61]). Serious complications occurred in the stent group, including 2 procedure-related deaths (3%), 1 late death secondary to an infected hematoma, and 1 patient who required dialysis secondary to cholesterol embolism. The groups did not differ for other secondary end points. LIMITATION: Many patients were falsely identified as having renal artery stenosis greater than 50% by noninvasive imaging and did not ultimately require stenting. CONCLUSION: Stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications. The study findings favor a conservative approach to patients with ARAS, focused on cardi

Contains fulltext : 70029.pdf (publisher's version ) (Closed access), Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.

Item does not contain fulltext, Since the introduction of the aldosterone-to-renin ratio (ARR ) as a screening tool for primary aldosteronism (PA), there has been a marked increase in the reported prevalence of this condition among hypertensive subjects. A meta-analysis from the literature shows a PA prevalence of almost 8% among hypertensive patients, with a twofold higher prevalence in referred patients as compared with primary care patients (9.0 vs 4.3%). However, the usefulness of the ARR remains subject of debate, because of doubts on its validity, and the many factors affecting the ARR , including posture, time of day of blood sampling, and use of antihypertensive medication. Furthermore, there is no clear cut-off value and it is unknown what population should be screened. Recently, The Dutch ARR AT Study was initiated. This is a multicentre, prospective trial aiming to evaluate the test characteristics of the ARR within a Dutch population of therapy-resistant hypertensive patients. The effect of antihypertensive medication on the ARR will be studied. Furthermore, from this study the prevalence of PA in this population will follow. Last, the blood pressure response to the selective aldosterone-receptor-antagonist eplerenone will be evaluated. The Dutch ARR AT Study will run until the end of 2009 and will contribute to the formulation of uniform guidelines for the screening for PA in the Netherlands.

Contains fulltext : 70029.pdf (publisher's version ) (Closed access), Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.

Item does not contain fulltext, Since the introduction of the aldosterone-to-renin ratio (ARR ) as a screening tool for primary aldosteronism (PA), there has been a marked increase in the reported prevalence of this condition among hypertensive subjects. A meta-analysis from the literature shows a PA prevalence of almost 8% among hypertensive patients, with a twofold higher prevalence in referred patients as compared with primary care patients (9.0 vs 4.3%). However, the usefulness of the ARR remains subject of debate, because of doubts on its validity, and the many factors affecting the ARR , including posture, time of day of blood sampling, and use of antihypertensive medication. Furthermore, there is no clear cut-off value and it is unknown what population should be screened. Recently, The Dutch ARR AT Study was initiated. This is a multicentre, prospective trial aiming to evaluate the test characteristics of the ARR within a Dutch population of therapy-resistant hypertensive patients. The effect of antihypertensive medication on the ARR will be studied. Furthermore, from this study the prevalence of PA in this population will follow. Last, the blood pressure response to the selective aldosterone-receptor-antagonist eplerenone will be evaluated. The Dutch ARR AT Study will run until the end of 2009 and will contribute to the formulation of uniform guidelines for the screening for PA in the Netherlands.

Item does not contain fulltext, Since the introduction of the aldosterone-to-renin ratio (ARR ) as a screening tool for primary aldosteronism (PA), there has been a marked increase in the reported prevalence of this condition among hypertensive subjects. A meta-analysis from the literature shows a PA prevalence of almost 8% among hypertensive patients, with a twofold higher prevalence in referred patients as compared with primary care patients (9.0 vs 4.3%). However, the usefulness of the ARR remains subject of debate, because of doubts on its validity, and the many factors affecting the ARR , including posture, time of day of blood sampling, and use of antihypertensive medication. Furthermore, there is no clear cut-off value and it is unknown what population should be screened. Recently, The Dutch ARR AT Study was initiated. This is a multicentre, prospective trial aiming to evaluate the test characteristics of the ARR within a Dutch population of therapy-resistant hypertensive patients. The effect of antihypertensive medication on the ARR will be studied. Furthermore, from this study the prevalence of PA in this population will follow. Last, the blood pressure response to the selective aldosterone-receptor-antagonist eplerenone will be evaluated. The Dutch ARR AT Study will run until the end of 2009 and will contribute to the formulation of uniform guidelines for the screening for PA in the Netherlands.

Contains fulltext : 58971.pdf (publisher's version ) (Closed access), The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that catalyses the formation of norepinephrine from dopamine. Inactivation of this enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic failure of the sympathetic nervous system. This manifests as a severe orthostatic syndrome in which sweating and a normal parasympathetic function are preserved. Several mutations of the DBH gene that cause this very rare syndrome have now been identified. Diagnosis is made on the basis of clinical features and the finding of increased plasma dopamine in the near-absence of norepinephrine. A sole finding of absent plasma DbetaH is insufficient, since about 4% of the population have absent DbetaH. This trait cosegregates with a polymorphism in the promoter region of the DBH gene and is not associated with sympathetic failure. The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by the ubiquitous aromatic-L-amino acid decarboxylase.

Contains fulltext : 58971.pdf (publisher's version ) (Closed access), The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that catalyses the formation of norepinephrine from dopamine. Inactivation of this enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic failure of the sympathetic nervous system. This manifests as a severe orthostatic syndrome in which sweating and a normal parasympathetic function are preserved. Several mutations of the DBH gene that cause this very rare syndrome have now been identified. Diagnosis is made on the basis of clinical features and the finding of increased plasma dopamine in the near-absence of norepinephrine. A sole finding of absent plasma DbetaH is insufficient, since about 4% of the population have absent DbetaH. This trait cosegregates with a polymorphism in the promoter region of the DBH gene and is not associated with sympathetic failure. The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by the ubiquitous aromatic-L-amino acid decarboxylase.

Contains fulltext : 58971.pdf (publisher's version ) (Closed access), The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that catalyses the formation of norepinephrine from dopamine. Inactivation of this enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic failure of the sympathetic nervous system. This manifests as a severe orthostatic syndrome in which sweating and a normal parasympathetic function are preserved. Several mutations of the DBH gene that cause this very rare syndrome have now been identified. Diagnosis is made on the basis of clinical features and the finding of increased plasma dopamine in the near-absence of norepinephrine. A sole finding of absent plasma DbetaH is insufficient, since about 4% of the population have absent DbetaH. This trait cosegregates with a polymorphism in the promoter region of the DBH gene and is not associated with sympathetic failure. The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by the ubiquitous aromatic-L-amino acid decarboxylase.

Item does not contain fulltext, BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

Item does not contain fulltext, Primary hyperaldosteronism (PHA), autonomic secretion of aldosterone by the adrenal gland, is rare. PHA usually results in therapy-resistant hypertension and is often but not always accompanied by hypokalaemia. Common causes of PHA are an aldosterone-producing adenoma, idiopathic aldosterone hypersecretion, unilateral hyperplasia or a genetic variant: glucocorticoid-remediable aldosteronism (GRA). The diagnosis should be phased and first of all requires a biochemical confirmation of the presence of PHA. In PHA patients, plasma renin is invariably suppressed. Blood should be collected under standardised conditions while the patient is not using beta-blockers or centrally-acting antihypertensive medication. Patients with a suppressed plasma renin and an elevated plasma aldosterone concentration have PHA. In patients with a suppressed plasma renin and a high-normal plasma aldosterone concentration a confirming test should be performed in which PHA is diagnosed if aldosterone is not suppressed following volume expansion with sodium chloride. The cause of PHA is determined by means of a CT scan or MRI of the adrenal glands to find a unilateral adenoma. If the CT scan or MRI is normal, adrenal vein aldosterone sampling may be considered as a next step in order to demonstrate lateralisation of aldosterone production. The hypertension and hypokalaemia of all forms of PHA respond well to spironolactone therapy. In the case of a unilateral adenoma or unilateral hyperplasia, adrenalectomy is the treatment of choice. For GRA, dexamethasone in doses that reduce the corticotropin (ACTH) level is indicated.

Item does not contain fulltext, BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

Item does not contain fulltext, Primary hyperaldosteronism (PHA), autonomic secretion of aldosterone by the adrenal gland, is rare. PHA usually results in therapy-resistant hypertension and is often but not always accompanied by hypokalaemia. Common causes of PHA are an aldosterone-producing adenoma, idiopathic aldosterone hypersecretion, unilateral hyperplasia or a genetic variant: glucocorticoid-remediable aldosteronism (GRA). The diagnosis should be phased and first of all requires a biochemical confirmation of the presence of PHA. In PHA patients, plasma renin is invariably suppressed. Blood should be collected under standardised conditions while the patient is not using beta-blockers or centrally-acting antihypertensive medication. Patients with a suppressed plasma renin and an elevated plasma aldosterone concentration have PHA. In patients with a suppressed plasma renin and a high-normal plasma aldosterone concentration a confirming test should be performed in which PHA is diagnosed if aldosterone is not suppressed following volume expansion with sodium chloride. The cause of PHA is determined by means of a CT scan or MRI of the adrenal glands to find a unilateral adenoma. If the CT scan or MRI is normal, adrenal vein aldosterone sampling may be considered as a next step in order to demonstrate lateralisation of aldosterone production. The hypertension and hypokalaemia of all forms of PHA respond well to spironolactone therapy. In the case of a unilateral adenoma or unilateral hyperplasia, adrenalectomy is the treatment of choice. For GRA, dexamethasone in doses that reduce the corticotropin (ACTH) level is indicated.

Item does not contain fulltext, Primary hyperaldosteronism (PHA), autonomic secretion of aldosterone by the adrenal gland, is rare. PHA usually results in therapy-resistant hypertension and is often but not always accompanied by hypokalaemia. Common causes of PHA are an aldosterone-producing adenoma, idiopathic aldosterone hypersecretion, unilateral hyperplasia or a genetic variant: glucocorticoid-remediable aldosteronism (GRA). The diagnosis should be phased and first of all requires a biochemical confirmation of the presence of PHA. In PHA patients, plasma renin is invariably suppressed. Blood should be collected under standardised conditions while the patient is not using beta-blockers or centrally-acting antihypertensive medication. Patients with a suppressed plasma renin and an elevated plasma aldosterone concentration have PHA. In patients with a suppressed plasma renin and a high-normal plasma aldosterone concentration a confirming test should be performed in which PHA is diagnosed if aldosterone is not suppressed following volume expansion with sodium chloride. The cause of PHA is determined by means of a CT scan or MRI of the adrenal glands to find a unilateral adenoma. If the CT scan or MRI is normal, adrenal vein aldosterone sampling may be considered as a next step in order to demonstrate lateralisation of aldosterone production. The hypertension and hypokalaemia of all forms of PHA respond well to spironolactone therapy. In the case of a unilateral adenoma or unilateral hyperplasia, adrenalectomy is the treatment of choice. For GRA, dexamethasone in doses that reduce the corticotropin (ACTH) level is indicated.

Item does not contain fulltext, BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.