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Background and Aims: Obstructive sleep apnea (OSA) may accelerate arterial calcification, but the relation remains unexplored in diabetic kidney disease (DKD). We examined the associations between OSA, coronary calcification and large artery stiffness in patients with DKD and reduced renal function., Methods: Patients with type 2 diabetes, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m 2 and urine albumin-creatinine ratio (UACR) > 30 mg/g were tested for OSA quantified by the apnea-hypopnea index (AHI, events/hour). Patients without OSA (AHI< 5) were compared to patients with moderate (AHI 15-29) or severe (AHI ≥30) OSA and underwent computed tomography angiography with coronary Agatston scoring (CAS) to quantify coronary calcification. Arterial stiffness was determined as carotid-femoral pulse wave velocity (PWV)., Results: Among 114 patients with acceptable AHI recordings had 43 no OSA, 33 mild OSA and 38 moderate-severe OSA. Mean age of the 74 patients completing the study was 71.5 ± 9.4 years (73% males), eGFR 32.2 ± 12.3 ml/min/1.73 m 2 and UACR 533 (192-1707) mg/g. CAS (ln-transformed) was significantly higher in patients with OSA compared to patients without (6.6 ± 1.7 vs. 5.6 ± 2.4, p = 0.04), and the same was observed for PWV (11.9 ± 2.7 vs. 10.5 ± 2.2 m/s, p = 0.02). In multivariable linear regression analyses adjusted for sex, age, body mass index, UACR, and mean arterial pressure, moderate-severe OSA remained significantly associated with PWV but not with CAS. Dominance analysis revealed OSA as the third and second most important factor relative to CAS and PWV respectively., Conclusions: In DKD patients, moderate-severe OSA is a significant predictor of arterial stiffness but is not independently associated with coronary calcification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Chronic kidney disease (CKD) is associated with accelerated vascular calcification and increased central systolic blood pressure when measured invasively (invCSBP) relative to cuff-based brachial systolic blood pressure (cuffSBP). The contribution of aortic wall calcification to this phenomenon has not been clarified. We, therefore, examined the effects of aortic calcification on cuffSBP and invCSBP in a cohort of patients representing all stages of CKD., Methods: During elective coronary angiography, invCSBP was measured in the ascending aorta with a fluid-filled catheter with simultaneous recording of cuffSBP using an oscillometric device. Furthermore, participants underwent a non-contrast computed tomography scan of the entire aorta with observer-blinded calcification scoring of the aortic wall ad modum Agatston., Results: We included 168 patients (mean age 67.0 ± 10.5, 38 females) of whom 38 had normal kidney function, while 30, 40, 28, and 32 had CKD stages 3a, 3b, 4, and 5, respectively. Agatston scores adjusted for body surface area ranged from 48 to 40,165. We found that invCSBP increased 3.6 (95% confidence interval 1.4-5.7) mm Hg relative to cuffSBP for every 10,000-increment in aortic Agatston score. This association remained significant after adjustment for age, diabetes, antihypertensive treatment, smoking, eGFR, and BP level. No such association was found for diastolic BP., Conclusions: Patients with advanced aortic calcification have relatively higher invCSBP for the same cuffSBP as compared to patients with less calcification. Advanced aortic calcification in CKD may therefore result in hidden central hypertension despite apparently well-controlled cuffSBP. ClinicalTrials.gov identifier: NCT04114695., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Ambulatory blood pressure monitoring (ABPM) may be stressful and associated with discomfort, possibly influenced by the number of cuff inflations. We compared a low frequency (LF-ABPM) regimen with one cuff inflation per hour, with a high frequency (HF-ABPM) regimen performed according to current guidelines using three cuff-inflations per hour during daytime and two cuff-inflations during night time. In a crossover study, patients underwent ABPMs with both frequencies, in a randomized order, within an interval of a few days. Patients reported pain (visual analogue scale from 0 to 10) and sleep disturbances after each ABPM. The primary endpoint was the difference in mean 24 h systolic BP (SBP) between HF-ABPM and LF-ABPM. A total of 171 patients were randomized, and data from 131 (age 58 ± 14 years, 47% females, 24% normotensive, 53% mildly hypertensive, and 22% moderately-severely hypertensive) completing both ABPMs were included in the analysis. Mean SBP was 137.5 mmHg (95% CI, 134.8;140.2) for HF-ABPM and 138.2 mmHg (95%CI, 135.2;141.1) for LF-ABPM. The 95% limits of agreement were -15.3 mmHg and +14.0 mmHg. Mean 24 h SBP difference between HF-ABPM and LF-ABPM was -0.7 mmHg (95%CI, -2.0;0.6). Coefficients of variation were similar for LF-ABPM and HF-ABPM. Pain scores (median with interquartile range), for HF-ABPM and LF-ABPM were 1.5 (0.6;3.0) and 1.3 (0.6;2.9) during daytime, and 1.3 (0.4:3.4) and 0.9 (0.4;2.0) during nighttime (P < 0.05 for both differences). We conclude that LF-ABPM and HF-ABPM values are in good agreement without any clinically relevant differences in BP. Furthermore, LF-ABPM causes a relatively modest reduction in procedure-related pain., (© 2023. The Author(s).)

Objective: The purpose of this study was to provide a more comprehensive look into the demographics of the veteran student subpopulation while exploring the relationship between the mental health of student veterans and their academic performance. Methods: A nationwide anonymous survey was distributed to student veterans who were enrolled in postsecondary institutions. Results: A large number of participants reported distress with symptoms of PTSD, depression, sleep disturbances, and/or suicidal ideation and attempts, and screened likely for mental health problems in these areas. Participants also endorsed academic problems ranging from the ability to stay focused to failing tests and quizzes. Additional findings demonstrated a positive association between GPA and both PTSD and depression. Conclusion: These findings can be used as a platform upon which to begin the discussion on the implications for mental health professionals, administrators, and educators.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m 2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P< 0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P <0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m 2 (95% CI, 4.5-11.1; P <0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.

Background: Little information exists on how COVID-19 testing influences intentions to engage in risky behavior. Understanding the behavioral effects of diagnostic testing may highlight the role of adequate testing on controlling viral transmission. In order to evaluate these effects, simulated scenarios were conducted evaluating participant intentions to self-isolate based on COVID-19 diagnostic testing availability and results., Methods: Participants from the United States were recruited through an online survey platform (Amazon Mechanical Turk) and randomized to one of three hypothetical scenarios. Each scenario asked participants to imagine having symptoms consistent with COVID-19 along with a clinical diagnosis from their physician. However, scenarios differed in either testing availability (testing available v. unavailable) or testing result (positive v. negative test). The primary outcome was intention to engage in high-risk COVID-19 behaviors, measured using an 11-item mean score (range 1-7) that was pre-registered prior to data collection. Multi-variable linear regression was used to compare the mean composite scores between conditions. The randomized survey was conducted between July 23rd to July 29th, 2020., Results: A total of 1400 participants were recruited through a national, online, opt-in survey. Out of 1194 respondents (41.6% male, 58.4% female) with a median age of 38.5 years, participants who had no testing available in their clinical scenario showed significantly greater intentions to engage in behavior facilitating COVID-19 transmission compared to those who received a positive confirmatory test result scenario (mean absolute difference (SE): 0.14 (0.06), P = 0.016), equating to an 11.1% increase in mean score risky behavior intentions. Intention to engage in behaviors that can spread COVID-19 were also positively associated with male gender, poor health status, and Republican party affiliation., Conclusion: Testing availability appears to play an independent role in influencing behaviors facilitating COVID-19 transmission. Such findings shed light on the possible negative externalities of testing unavailability., Trial Registration: Effect of Availability of COVID-19 Testing on Choice to Isolate and Socially Distance, NCT04459520, https://clinicaltrials.gov/ct2/show/NCT04459520., Competing Interests: No competing interests are noted by any of the listed authors.

A 16-year-old patient presented with abdominal pain and sustained hypertension. Thorough evaluation including renography with and without captopril and renal vein renin sampling were normal. Duplex ultrasound, however, raised suspicion of a renal artery stenosis. This was confirmed by computed tomography angiography which showed a severe branch artery stenosis with post-stenotic dilatation consistent with focal fibromuscular dysplasia (FMD). As the hypertension was resistant to 3 classes of antihypertensive treatment, percutaneous transluminal renal angioplasty (PTRA) was offered. The procedure had immediate effect on the blood pressure. Without medication the patient remains normotensive 4 years after and the abdominal pain has only sporadically returned. The presented case illustrates the challenging process of diagnosing FMD-related renal branch artery stenosis as well as the potential benefits of PTRA in this patient group.

Purpose: Twenty-four hours of ambulatory blood pressure monitoring (ABPM) is recommended in several guidelines as the best method for diagnosing hypertension. In general, the prognostic value of ABPM is superior to single office blood pressure (BP) measurements. Unfortunately, some patients experience considerable discomfort during frequently repeated forceful cuff inflations., Materials and Methods: In this study we investigated the difference in mean daytime systolic BP (SBP) between low-frequency ABPM (LF-ABPM), measuring once every hour, and high-frequency ABPM (HF-ABPM), measuring three times an hour during daytime, and two times an hour during night-time., Results: Seventy-one patients were included in the analysis. All included patients had an HF-ABPM performed first and within a few weeks they underwent an LF-ABPM. The average day time difference in SBP between the two frequencies was 3.8 mmHg ( p -value = 0.07) for mild, 8.2 mmHg ( p -value < 0.01) for moderate and 15 mmHg ( p -value < 0.001) for severe hypertension. A similar pattern was seen for night-time SBP. This study suggests that mean BP is similar between the two measuring frequencies for normotensive and mild hypertensive patients, while HF-ABPM results in a higher 24-h mean BP for moderate- and severe hypertensive patients., Conclusion: LF-ABPM may more correctly reflect the resting blood pressure in patients with moderate and severe hypertension.

Background: Blood pressure (BP) control is important in chronic kidney disease (CKD), but a reduction in brachial BP may not mirror changes in central aortic BP (cBP) during antihypertensive medication. We hypothesize that a fall in cBP is better reflected during enhanced vasodilation treatment (EVT) compared with reduced vasodilation treatment (RVT) because of different hemodynamic actions of these interventions., Methods: Eighty-one hypertensive CKD stage 3-4 patients (mean measured glomerular filtration rate 36 ml/min per 1.73 m2) were randomized to either EVT based on renin--angiotensin blockade and/or amlodipine or RVT based on nonvasodilating β-blockade (metoprolol). Before randomization and following 18 months of treatment, we performed 24-h ambulatory BP measurements (ABPM) and radial artery pulse wave analysis for estimation of cBP and augmentation index (AIx). Forearm resistance (Rrest) was determined by venous occlusion plethysmography and arterial stiffness by carotid--femoral pulse wave velocity (PWV). Matched healthy controls were studied once for comparison., Results: Compared with controls, CKD patients had elevated ABPM, cBP and PWV. Although ABPM remained unchanged from baseline to follow-up in both treatment groups, cBP decreased 4.7/2.9 mmHg (systolic/diastolic) during EVT and increased 5.1/1.5 mmHg during RVT (Δ=9.8/4.4 mmHg, P=0.02 for SBP, P = 0.05 for DBP). At follow-up, the difference between systolic cBP and 24-h ABPM (ΔBPsyst) was negatively associated with heart rate and positively associated with AIx and Rrest (all P < 0.01) but not PWV (P = 0.32)., Conclusion: In CKD patients, EVT and RVT have opposite effects on cBP and the difference between cBP and ambulatory BP is larger for EVT than RVT., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Repeated cuff-based blood pressure (BP) measurements may cause discomfort resulting in stress and erroneous recording values. SOMNOtouch NIBP is an alternative cuff-less BP measurement device that calculates changes in BP based on changes in pulse transit time (PTT) and a software algorithm. The device is calibrated with a single upper arm cuff-based BP measurement. We tested the device against a validated 24-h ambulatory BP monitoring (ABPM) device using both the previous (SomBP1) and the current software algorithm (SomBP2). In this study, 51 patients (mean age ± SD 61.5 ± 13.0 years) with essential hypertension underwent simultaneous 24-h ABPM with the SOMNOtouch NIBP on the left arm and a standard cuff-based oscillometric device on the right arm (OscBP). We found that mean daytime systolic BP (SBP) with OscBP was 140.8 ± 19.7 compared to 148.0 ± 25.2 (P = .008) and 146.9 ± 26.0 mmHg (P = .034) for SomBP1 and SomBP2, respectively. Nighttime SBP with OscBP was 129.5 ± 21.1 compared with 146.1 ± 25.8 (P < .0001) and 141.1 ± 27.4 mmHg (P = .001) for SomBP1 and SomBP2, respectively. Ninety-five% limits of agreement between OscBP and SomBP1 were ± 36.6 mmHg for daytime and ± 42.6 mmHg for nighttime SBP, respectively. Agreements were not improved with SomBP2. For SBP, a nocturnal dipping pattern was found in 33% of the study patients when measured with OscBP but only in 2% and 20% with SomBP1 and -2, respectively. This study demonstrates that BP values obtained with the cuff-less PTT-based SOMNOtouch device should be interpreted with caution as these may differ substantially from what would be obtained from a validated cuff-based BP device., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Troponin T (TnT) is a well-known risk factor for negative outcome in hemodialysis (HD) patients, but little is known about variation over time, and the impact of clinical and dialysis specific factors. This study investigated the effect of angiotensin II receptor blockade (ARB), short and long-term variation in TnT and associations with clinical parameters., Methods: In this analysis based on the SAFIR-cohort (Clinical Trials ID: NCT00791830) 81 HD patients were randomized double-blind for placebo (n = 40) or angiotensin II receptor blocker (ARB) treatment (n = 41) with irbesartan (150-300 mg) and followed for 12 months with six serial measurements of TnT using a high-sensitivity assay., Results: Fifty-four patients (67%) completed follow-up. Baseline TnT-medians (min-max) were (placebo/ARB): 45(14-295)/46(10-343) ng/L. ARB-treatment did not significantly affect mean TnT-levels over the 12-month study period. Median week-to-week and one-year TnT-variation (5th-95th-percentile range) using all samples regardless of intervention were: 0(- 14-10) ng/L (week-to-week) and 3(- 40-71) ng/L (12 months). Median TnT-amplitude, capturing the change from the lowest to the highest TnT-value observed during the one-year study period was 38% or 20.5 ng/L. Median ratios with 95% limits of agreement were: 1.00(0.73-1.37); P = 0.92 (1 week/baseline; n = 77) and 1.07(0.52-2.25); P = 0.19 (12 months/baseline; n = 54). Baseline TnT was positively correlated with diabetes, ultrafiltration volume, arterial stiffness, change in intradialytic total peripheral resistance and N-terminal pro b-type natriuretic peptide (NT-proBNP) and negatively correlated with hematocrit, residual renal function and change in intradialytic cardiac output. High baseline TnT was associated with a higher risk of admission and cardiovascular (CV) events during follow-up. Increase in TnT over time (ΔTnT = 12-months-baseline) was significantly associated with increase in left ventricular (LV) mass and NT-proBNP and decrease in LV ejection fraction and late intradialytic stroke volume. ΔTnT was not significantly associated with admissions, CV or intradialytic hypotensive events during follow-up. Admissions were significantly more likely with a high (TnT-amplitude> 20.5 ng/L) than a low TnT-amplitude. Peaks in TnT were less frequent in aspirin-treated patients., Conclusion: ARB-treatment had no significant effect on TnT-levels. Week-to-week variation was generally low, yet over 12 months individual patients had considerable TnT fluctuations. Rise in TnT over time was significantly correlated with markers of cardiac deterioration., Trial Registration: ClinicalTrials.gov Identifier: NCT00791830 . Date of registration: November 17, 2008. EudraCT no: 2008-001267-11.

In this report, we present a challenging case of a 63-year-old Caucasian woman with an extreme stress response to blood pressure (BP) measurements. Office- and ambulatory BP measurements consistently found systolic BP above 200 mmHg. However, antihypertensive medication made her dizzy and extremely unwell, and she could barely tolerate treatment with a moderate dose of angiotensin-converting enzyme (ACE) inhibitor. Finger-cuff-based measurements (Finapres Finometer®) revealed extreme hypertension in relation to contact with medical professionals, but hypotension when the patient was seated alone unobserved. Months after, the patient suffered a hemorrhagic stroke possibly related to her extreme BP-fluctuations in stressful situations.

It is recommended that advance care planning take place across the lifespan. Rural populations have a heightened risk for poor quality and high cost of end-of-life care. A doctoral project was completed to assess rural nurses' knowledge, attitudes, and experiences with advance directives using the Knowledge, Attitudinal, and Experimental Surveys on Advance Directives. Descriptive statistics were used for analysis. Participants were nurses who practice in rural settings (N = 22). The average age was 46.4 years; all were white (n = 22), and the majority were baccalaureate prepared (n = 12). Practice settings were primarily in home care and hospice. Knowledge scores on advance directives were low (57%). Nurses felt confident in counseling and initiating discussions with patients and families. Less than one-half of the nurses reported they feel part of the advance care planning team. The majority reported advance directive resources and mentorship of younger nurses would be beneficial and indicated the need for additional education, training, knowledge, time, and support to better assist with advance care planning. Project results and recommendations were presented to the participating health care organization. Recommendations included workplace education, support, mentorship, resources, and education on cultural sensitivity using the rural nursing theory.

Aim: Progression of chronic kidney disease (CKD) may be accelerated by tissue hypoxia due to impaired blood supply. This could be induced by small artery narrowing resulting in abnormally high intrarenal vascular resistance (RVR). We investigated whether a reduction in RVR achieved by adding vasodilating medical therapy (AVT) is superior to adding nonvasodilating medical therapy (AnonVT) regarding tissue oxygenation and preservation of kidney function., Methods: Eighty-three grade 3 and 4 CKD patients [estimated glomerular filtration rate (GFR) 34.6 ml/min per 1.73 m] were randomized to either AVT with amlodipine and/or renin angiotensin blockade or AnonVT with the nonvasodilating beta-blocker metoprolol. Investigations were performed at baseline and after 18 months of therapy. Systemic vasodilation was documented in the forearm vasculature using resting venous occlusion plethysmography. GFR was measured as Chrome-EDTA plasma clearance. Using MRI, renal artery blood flow was measured for calculation of RVR and for estimating renal oxygenation (R2*)., Results: AVT and AnonVT achieved as planned similar blood pressure levels throughout the study. At follow-up, resistance had decreased by 7% (P < 0.05) and RVR by 12% (P < 0.05) in the AVT group, whereas in the AnonVT group, resistance increased by 39% (P < 0.01), whereas RVR remained unchanged. At follow-up, no significant differences in cortical or medullary R2* values between AVT and AnonVT were observed, and the GFR decline was similar in the two groups (3.0 vs. 3.3 ml/min per 1.73 m)., Conclusion: Long-term intensified vasodilation treatment reduced peripheral and RVR, but this was not associated with improvement of R2* or protection against loss of kidney function in CKD patients.

Background and Aims: Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score., Methods: A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROC AUC models., Results: 1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01-1.34) and 1.04 (95% CI 1.01-1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45-2.84) and 60-year-old subjects (1.44; 95% CI 1.09-1.90). By ROC AUC , neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32)., Conclusions: Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Changes in the organisation of chronic healthcare, an increased awareness of costs and challenges of low adherence in cardiac rehabilitation (CR) call for the exploration of more flexible CR programmes as alternatives to hospital-based CR (H-CR). A model of shared care cardiac rehabilitation (SC-CR) that included general practitioners and the municipality was developed. The aim of this study was to analyse the cost utility of SC-CR versus H-CR., Methods: The cost-utility analysis was based on a randomised controlled trial of 212 patients who were allocated to SC-CR or H-CR and followed up for 12 months. A societal cost perspective was applied that included the cost of intervention, informal time, healthcare and productivity loss. Costing was based on a microcosting approach for the intervention and on national administrative registries for the other cost categories. Quality-adjusted life years (QALYs) were based on the EuroQol 5-Dimensions measurements at baseline, after 4 months and after 12 months. Conventional cost-effectiveness methodology was employed to estimate the net benefit of SC-CR., Results: The average cost of SC-CR was 165.5 kDKK and H-CR 163 kDKK. Productivity loss comprised 74.1kDKK and 65.9 kDKK. SC-CR cost was an additional 2.5 kDKK (95% CI -38.1 to 43.1) ≈ (0.33; -5.1 to 5.8 k€) and a QALY gain of 0.02 (95% CI -0.03 to 0.06). The probability that SC-CR would be cost-effective was 59% for a threshold value of willingness to pay of 300 kDKK (k€40.3)., Conclusion: CR after shared care model and H-CR are comparable and similar in socioeconomic terms., Trial Registration Number: NCT01522001; Results., Competing Interests: Competing interests: None declared.

Background: Microvascular impairment is well documented in hypertension. We investigated the effect of renal sympathetic denervation (RDN) on cardiac and peripheral microvasculature in patients with treatment-resistant essential hypertension (TRH)., Methods: A randomized, single centre, double-blinded, sham-controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP (ASBP) ≥ 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin) were determined using transthoracic Doppler echocardiography and F-Rmin with venous occlusion plethysmography at baseline and at six-months follow-up., Results: RDN was performed with 5.3±0.2 lesions in the right renal artery and 5.4±0.2 lesions in the left. Baseline ASBP was 152±2mmHg (RDN, n=29) and 154±2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (-3.5±2.0 vs. -3.2±1.8, P=0.92). Baseline CFR was 2.9±0.1 (RDN) and 2.4±0.1 (SHAM), with no significant change at follow-up (0.2±0.2 vs. -0.1±0.2, P=0.57). C-Rmin was 1.9±0.3 (RDN) and 2.7±0.6 (SHAM) (mmHgmin/ml pr. 100g) and did not change significantly (0.3±0.5 vs. -0.4±0.8, P=0.48). F-Rmin was 3.6±0.2 (RDN) and 3.6±0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged at follow-up (4.2±0.4 vs. 3.8±0.2, P=0.17). Left ventricular mass index was unchanged following RDN (-4±7 (RDN) vs. 3±5 (SHAM) (g/m 2 ) P=0.38)., Conclusion: The current study does not support positive effects of RDN on microvascular impairment in TRH., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension., Methods: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity Flex TM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor ® -device., Results: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN., Conclusions: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension., Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of  ≥145 mm Hg, and/or a daytime diastolic ABPM of  ≥95 mm Hg after witnessed drug intake (including  ≥3 antihypertensive drugs, preferably including a diuretic)., Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety., Conclusions: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.

Traditional office blood pressure (OBP) measurement as performed in busy outpatient clinics agrees poorly with awake ambulatory BP, and generally BP is severely overestimated. Especially elderly patients may be overtreated with the risk of symptomatic hypotension and fall injuries. Furthermore, truly high OBP measurements are often ignored as white coat hypertension, which leads to undertreatment of hypertension in high-risk individuals. Traditional OBP is thus of limited use and may even be harmful. Better methods are available and should be implemented.

Aim: To investigate whether phase II cardiac rehabilitation (CR) conducted by a community model of shared care CR (SC-CR) including health care centres and general practice was feasible and provided acceptable results and to compare SC-CR to hospital-based CR (H-CR) in a randomised controlled trial., Methods: Patients were randomised to H-CR or SC-CR after admission for acute coronary syndrome. In SC-CR, the general practitioner took over the responsibility of the remaining rehabilitation, pharmacological treatment and risk factor management after the initial visit to the hospital outpatient clinic. The Municipal Health Care Centres provided courses on smoking cessation, nutrition, and exercise training and contributed to disease education and psychosocial support. The main endpoint was adherence to the CR programme and compliance with lifestyle modifications., Results: In total, 1364 patients were screened, 327 (24%) were eligible, and 212 (65%) accepted participation. Phase II CR was completed by 192 (91%) of the participants. Full adherence to the CR programme was seen in 53% in SC-CR versus 54% in H-CR (relative risk (RR): 0.98, 95% confidence interval: 0.73-1.32). In H-CR, patients had higher rates of adherence to dietary advice and health education. In SC-CR, 12% of patients did not attend the risk factor evaluation and clinical assessment with their general practitioner. No difference in risk factor improvement was found. Exercise training was declined by 25% in both groups., Conclusion: Adherence to phase II CR was high in both groups. SC-CR did not improve adherence and efficacy, but had comparable effects on medication and risk factors. Thus, SC-CR was safe and effective.

Increased sympathetic activity is important in the pathogenesis of hypertension and insulin resistance. Afferent signaling from the kidneys elevates the central sympathetic drive. We investigated the effect of catheter-based renal sympathetic denervation (RDN) on glucose metabolism, inflammatory markers, and blood pressure in nondiabetic patients with treatment-resistant hypertension. Eight subjects were included in an open-labelled study. Each patient was studied before and 6 months after RDN. Endogenous glucose production was assessed by a 3- 3 H glucose tracer, insulin sensitivity was examined by hyperinsulinemic euglycemic clamp, hormones and inflammatory markers were analyzed, and blood pressure was measured by office blood pressure readings and 24-hour ambulatory blood pressure monitoring. Insulin sensitivity ( M -value) increased nonsignificantly from 2.68 ± 0.28 to 3.07 ± 0.41 ( p = 0.12). A significant inverse correlation between the increase in M -value and BMI 6 months after RDN ( p = 0.03) was found, suggesting beneficial effects on leaner subjects. Blood pressure decreased significantly, but there were no changes in hormones, inflammatory markers, or endogenous glucose production. Our results indicate that RDN may improve insulin sensitivity in some patients with treatment-resistant hypertension, albeit confirmation of these indications of beneficial effects on leaner subjects awaits the outcome of larger randomized controlled studies.

Introduction: Low-grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti-inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients., Methods: Adult HD patients were randomized for double-blind treatment with the ARB irbesartan 150-300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6, IL-8, IL-18, and transforming growth factor-β (TGF-β) were measured using Luminex and enzyme-linked immunosorbent assay (ELISA) technology., Findings: Eighty-two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2-23.4)/2.7(0.2-29.6) μg/mL; IL-1β 1.1(0.0-45.9)/1.1(0.0-7.2) pg/mL; IL-6 10(1-90)/12(1-84) pg/mL; IL-8 31(9-134)/34(5-192) pg/mL; IL-18 364(188-1343)/377(213-832) pg/mL; TGF-β 3.2(0.8-13.9)/3.6(1.3-3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between placebo and ARB-treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL-1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL-18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB-treated (P ≥ 0.51 in tests for parallel curves and equal levels)., Discussion: Inflammatory biomarkers were neither acutely, nor in the long-term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti-inflammatory effects., (© 2016 International Society for Hemodialysis.)

Objective: We investigated the agreement between elevated outpatient clinic office blood pressure (OC-OBP) as measured in the daily routine in our University Hospital Cardiology Outpatient Clinic and subsequent awake ambulatory blood pressure (AABP)., Methods: In all patients referred for ambulatory blood pressure monitoring from our Cardiology Outpatient Clinic, we identified OC-OBP and changes in medication in the period from 1 January 2014 to 15 September 2015. The AABP was used as a reference measurement for the OC-OBP., Results: A total of 183 patients were included in the study. Their mean age was 62.1±14.0 years and 49% were women. The mean systolic OC-OBP was 166.8±17.9 mmHg and the difference between the mean systolic OC-OBP and AABP was 28.0±19.5 mmHg (P<0.001) with 95% limits of agreement from -10.2 to +66.3 mmHg. The difference in mean systolic OC-OBP and AABP was 18.6±14.7 mmHg in patients less than 45 years (n=21), 24.8±18.2 mmHg in patients 45-74 years (n=121) and 42.3±18.5 mmHg in patients more than or equal to 75 years (n=41). In 32 (17%) of the patients, the antihypertensive treatment was intensified before the AABP, but in nine (28%) of these patients, the antihypertensive treatment was reduced again after the AABP because of low blood pressure., Conclusion: Routine OC-OBP in a busy cardiology clinic agrees poorly with AABP and may lead to unnecessary treatment and pharmacologically induced symptomatic hypotension, particularly in elderly patients. The results of this study urgently call for alternative solutions to routine OC-OBP in hospital outpatient clinics.

Increased systemic vascular resistance and coronary microvascular dysfunction are well-documented in essential hypertension (EH). We investigated the effect of additional vasodilating treatment on coronary and peripheral resistance circulation in EH patients with high systemic vascular resistance index (SVRI) despite well-treated blood pressure (BP). We enroled patients on stable antihypertensive treatment that were given intensified vasodilating therapy (ACE inhibitor, angiotensin II receptor blocker or calcium channel blocker). Before and following 6 months of intensified therapy, coronary resting and maximal artery flow were measured by transthoracic Doppler echocardiography to calculate coronary flow reserve (CFR) and minimum vascular resistance (C-R min ). Cardiac output was estimated by inert gas rebreathing to calculate SVRI. Maximal forearm blood flow was determined by venous occlusion plethysmography to calculate minimum vascular resistance (F-R min ). Patients were assigned into two groups: high-SVRI and low-SVRI subgroups, based on a median split at baseline. Following additional treatment SVRI decreased more in the high-SVRI group than in the low-SVRI group (14.4 vs -2.2%: P=0.003), despite similar baseline ambulatory BP (132/81 mm Hg) and BP reduction (6.5 and 4.6%: P=0.19). F-R min remained unchanged (6.5 vs -2.0%: P=0.30), while C-R min decreased by 22 and 24% (P=0.80) and CFR increased by 23 and 17% (P=0.16). Thus, intensified vasodilating therapy improved SVRI more in patients with high SVRI than in those with low SVRI. Regardless of SVRI status, the treatment improved cardiac but not forearm dilatation capacity. The substantial improvement of the hypertensive cardiac microvascular dysfunction was not related to the reduction in SVRI.

Objectives: Occupational and residential noise exposure has been related to increased risk of cardiovascular disease. Alteration of serum lipid levels has been proposed as a possible causal pathway. The objective of this study was to investigate the relation between ambient and at-the-ear occupational noise exposure and serum levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides when accounting for well-established predictors of lipid levels., Methods: This cross-sectional study included 424 industrial workers and 84 financial workers to obtain contrast in noise exposure levels. They provided a serum sample and wore portable dosimeters that every 5-s recorded ambient noise exposure levels during a 24-h period. We extracted measurements obtained during work and calculated the full-shift mean ambient noise level. For 331 workers who kept a diary on the use of a hearing protection device (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the mean full-shift noise exposure level at the ear., Results: Mean ambient noise level was 79.9 dB (A) [range 55.0-98.9] and the mean estimated level at the ear 77.8 dB (A) [range 55.0-94.2]. Ambient and at-the-ear noise levels were strongly associated with increasing levels of triglycerides, cholesterol-HDL ratio, and decreasing levels of HDL-cholesterol, but only in unadjusted analyses that did not account for HPD use and other risk factors., Conclusion: No associations between ambient or at-the-ear occupational noise exposure and serum lipid levels were observed. This indicates that a causal pathway between occupational and residential noise exposure and cardiovascular disease does not include alteration of lipid levels.

Background: Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP., Method: We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA)., Results: We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial., Conclusion: Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Objectives Previous studies have suggested that urine albumin excretion (UAE) mirrors generalized vascular damage; however, it is unclear to which degree UAE mirrors small artery impairment. Design We enrolled 67 patients with uncomplicated essential hypertension (EH) during stable antihypertensive therapy. F-Rmin, ACR on three non-consecutive morning urine samples, pulse wave velocity (PWV), and 24-h ambulatory blood pressure (ABPM) were measured. Results ACR was low (0.39 and 0.30-0.60), but abnormal small artery structure defined as F-Rmin > mean + 2 standard deviations of normotensive value (1.99 + 1 mmHg min/(ml/100 ml)) was present in 45% (n = 30). The mean F-Rmin was 2.89 ± 0.09 mmHg min/(ml/100 ml). ACR correlated significantly to PWV (r(2 )=( )0.11; p < 0.05) and pulse pressure (r(2 )=( )0.15; p < 0.001), but not F-Rmin and (r(2 )=( )0.05, p = 0.07). Conclusions Abnormal microvascular structure was present even in EH patients with low UAE. ACR correlated to arterial stiffness and not to small artery structure; therefore, UEA did not reflect microvascular damage in this population. ACR and F-Rmin thus reflect two distinct types of subclinical organ damage in hypertension.

Aim: Young individuals genetically predisposed for essential hypertension have increased renal vascular resistance. We evaluated whether 1 year of angiotensin II receptor blockade decreases afferent arteriolar resistance (RA) and induces a sustained blood pressure (BP) reduction during a 10-year follow-up period in offspring of parents both diagnosed with essential hypertension., Methods: Based on renal plasma flow (p-aminohippurate clearance) and glomerular filtration rate (Cr-EDTA clearance) RA was calculated according to the model originally established by Gomez. Following baseline measurements, the participants (n = 110, mean age 30 years) were randomly allocated to 12 months of treatment with either candesartan or placebo followed by repetition of measurements and withdrawal of medication. Four-hour ambulatory BP (ABP) was recorded at baseline, by end of active treatment and after 6 months, 1, 2, 3, 5, and 10 years. ABP was analyzed according to RA achieved at the end of active treatment., Results: Candesartan reduced RA by 14% (P < 0.01). Ten years posttreatment systolic ABP increased by 2.1 mmHg (P = 0.04) and diastolic by 4.2 mmHg (P < 0.01) compared with baseline, without any difference between treatment arms. A high posttreatment RA was associated with higher BP levels during follow-up, but long-term alterations in 24-h BP were similar in participants with low and high RA and not different between treatment arms., Conclusion: RA is associated with 24-h BP levels, but temporary lowering of BP and RA by candesartan does not prevent BP from increasing further. Prevention of hypertension appears not feasible by short-term inhibition of the rennin-angiotensin system in young adults.

Large artery stiffness and small artery structural changes are both cardiovascular risk factors. Arterial stiffness increases with age and blood pressure (BP), but it is unclear in which way large artery pulse wave velocity (PWV) and peripheral vascular resistance are related and whether age has any influence. In a cross-sectional study, PWV and forearm minimum vascular resistance (Rmin ) was compared with emphasis on the impact of age. Normotensive (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24-h BP measurements. Age ranged from 21 to 79 years with an even distribution from each age decade. PWV was assessed using tonometry. Forearm Rmin was measured by venous occlusion plethysmography at maximal vasodilatation induced by 10 min of ischaemia in combination with skin heating and hand grip exercise. In both normotensive and hypertensive subjects, PWV correlated significantly with age and BP. Based on median age, both groups were assigned into two equally large subgroups. Normotensive older (66 ± 7 years) and younger (35 ± 10 years) persons had different carotid-femoral PWV (7.9 ± 1.8 versus 5.7 ± 0.9 m/s, P<0.01), but similar Rmin values (3.7 ± 0.9 versus 3.6 ± 1.2 mmHg/ml/min/100 ml). Hypertensive older (63 ± 6 years) and younger (40 ± 10 years) also had different PWV (8.0 ± 1.5 versus 6.7 ± 1.1 m/s, P<0.05), but the older had lower Rmin (3.1 ± 0.8 versus 4.7 ± 2.2 mmHg/ml/min/100 ml, P<0.05). In a regression analysis adjusting for age, BP, gender and heart rate, no correlation was seen between PWV and Rmin . The data suggest that age differentially affects PWV and Rmin and that BP can increase in older persons without affecting Rmin ., (© 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background and Aim: Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan., Design: Randomized, double-blind, placebo-controlled, one-year intervention trial., Setting and Participants: Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year., Intervention: Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients., Outcomes and Measurements: Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension., Results: At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters., Conclusion: Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen., Trial Registration: Clinicaltrials.gov NCT00791830.

Bisphenol A (BPA) is used in the manufacture of a range of consumer products, and human biomonitoring studies suggest that exposure to BPA is nearly ubiquitous. We constructed and calibrated a simple pharmacokinetic model to predict urinary concentrations of BPA based on a known initial dose. This descriptive (rather than physiologically based) model has three compartments: "stomach/liver," "blood," and "bladder." We calibrated and validated the model parameters using blood and urine measurements from nine volunteers who consumed 5 mg of d₁₆-BPA. We then applied the model to a second group of eight persons, who supplied full volumes of urine over 7 consecutive days and a diary identifying times and types of food and beverage consumed, to "reconstruct" the time and mass of BPA intakes. These reconstructed daily intakes ranged on average from 60 to 100 ng/kg-day, within the range of, but slightly higher than, those surmised from other studies. About two-thirds of intakes occurred within an hour of reported food or drink consumption, supporting the hypothesis that diet is the main pathway of exposure to BPA. However, one-third of all reconstructed intakes took place outside this time window, suggesting that other sources of BPA exposure may also be relevant.

Purpose: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication., Methods: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish National Prescription Registry. Odds ratios (OR) comparing the highest and lowest third of the population at individual and work-unit level, respectively, were estimated by multilevel logistic regression adjusted for confounders. Psychological demands and decision latitude were tested for interaction. Supplementary analyses of 21 months follow-up were conducted., Results: Among women, increasing psychological demands at individual (adjusted OR 1.54; 95 % CI 1.02-2.33) and work-unit level (adjusted OR 1.41; 95 % CI 1.04-1.90) was significantly associated with purchase of antihypertensive medication. No significant association was found for decision latitude. Follow-up results supported an association with psychological demands but they were not significant. All results for men showed no association. Psychological demands and decision latitude did not interact., Conclusion: High psychological work demands were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job strain model.

Agents blocking the renin-angiotensin-aldosterone system are frequently used in patients with end-stage renal disease, but whether they exert beneficial cardiovascular effects is unclear. Here the long-term effects of the angiotensin II receptor blocker, irbesartan, were studied in hemodialysis patients in a double-blind randomized placebo-controlled 1-year intervention trial using a predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group of 41 patients did not differ in terms of age, blood pressure, comorbidity, antihypertensive treatment, dialysis parameters, and residual renal function. Brachial blood pressure decreased significantly in both groups, but there was no significant difference between placebo and irbesartan. Use of additional antihypertensive medication, ultrafiltration volume, and dialysis dosage were not different. Intermediate cardiovascular end points such as central aortic blood pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N-terminal brain natriuretic prohormone, heart rate variability, and plasma catecholamines were not significantly affected by irbesartan treatment. Changes in systolic blood pressure during the study period significantly correlated with changes in both left ventricular mass and arterial stiffness. Thus, significant effects of irbesartan on intermediate cardiovascular end points beyond blood pressure reduction were absent in hemodialysis patients.

Exposures to multiple chemicals may contribute to increased risk of similar adverse effects. Cumulative risk may be estimated using a hazard index (HI), the sum of individual hazard quotients (HQ, ratio of exposure to the reference value). We demonstrate the HI approach for five phthalates: di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diisobutyl phthalate (DiBP), diisononyl phthalate (DiNP), and butyl benzyl phthalate (BBP). Phthalate exposure for the US general population is estimated using urine metabolite levels from NHANES, extrapolating to ingested 'dose' using the creatinine correction approach. We used two sets of reference values: European Union Tolerable Daily Intakes and Denmark Environmental Protection Agency Derived No Effect Levels. We also investigated the use of an alternate reference value for DEHP, derived from a recent study on male reproductive system development. HQs and HIs were calculated for the total population ages 6years and older, as well as for men and women of approximate reproductive age (18-39 years), and children (6-11 years). Median HQs ranged from <0.01 for BBP, to ∼0.1 (using established values) or ∼2 (using an alternate value) for DEHP. Median HIs were <0.30 (95th percentiles just >1.0), and were driven by DEHP and DBP exposures., (Published by Elsevier Inc.)

Introduction: The few extant Danish studies on e-mail consultations were undertaken before it became manda-tory under Danish law to offer patients this form of consultation. This study investigates the ways in which patients and general practitioners communicate with each other by e-mail, explores factors influencing this means of communication and puts into perspective the potential of e-mail consultations in patient treatment., Material and Methods: The study is explorative and based on an individual interview and four qualitative focus group interviews. The empirical data were analysed from a social constructivist and a practice-theoretical approach., Results: The study indicated that patients wanted to be able to use the general practitioner (GP) as a sparring partner in e-mail consultations. They expected a reply in case of uncertainties. The GPs found it difficult to handle complicated medical problems by e-mail and they tended to send a standard reply. A number of patients perceived the wording of the standard reply as a rejection of their problem. Patients highlighted the logistical advantages of e-mail consultations, the physical separation of doctor and patient which made it easier for them to disclose psychological or intimate issues. The GPs preferred short uncomplicated questions with no option for the patient to enter into a discussion., Conclusion: Patients and GPs have different approaches to e-mail. The development of clear guidelines for patients and revised guidelines for GPs regarding e-mail consultations is therefore recommended., Funding: not relevant., Trial Registration: journal no. 2012-41-0063 with the Danish Data Protection Agency.

Environmental and occupational noise exposure have been related to increased risk of cardiovascular disease, hypothetically mediated by stress-activation of the hypothalamic-pituitary-adrenal (HPA) axis. The objective of this study was to investigate the relation between recent and long-term occupational noise exposure and cortisol level measured off work to assess a possible sustained HPA-axis effect. We included 501 industrial, finance, and service workers who were followed for 24h during work, leisure, and sleep. Ambient occupational noise exposure levels were recorded every 5s by personal dosimeters and we calculated the full-shift LAEq value and estimated duration and cumulative exposure based on their work histories since 1980. For 332 workers who kept a log-book on the use of hearing protection devices (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the noise level at the ear. Salivary cortisol concentration was measured at 20.00 h, the following day at awakening, and 30 min after awakening on average 5, 14 and 14.5h after finishing work. The mean ambient noise exposure level was 79.9 dB(A) [range: 55.0-98.9] and the mean estimated level at the ear 77.7 dB(A) [range: 55.0-94.2]. In linear and mixed regression models that adjusted for age, sex, current smoking, heavy alcohol consumption, personal income, BMI, leisure-time noise exposure level, time since occupational noise exposure ceased, awakening time, and time of saliva sampling, we observed no statistically significant exposure response relation between recent, or long-term ambient occupational noise exposure level and any cortisol parameter off work. This was neither the case for recent noise level at the ear. To conclude, neither recent nor long-term occupational noise exposure levels were associated with increased cortisol level off work. Thus, our results do not indicate that a sustained activation of the HPA axis, as measured by cortisol, is involved in the causal pathway between occupational noise exposure and cardiovascular disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are not often studied together. Many of these chemicals may be hepatotoxic. We used the 2003-2004 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 37 environmental contaminants, comprising heavy metals, non-dioxin-like polychlorinated biphenyls (PCBs), and dioxin-like compounds, using a novel method. Linear regression models were constructed for each chemical separately, then as a class, using quartiles to represent exposure and adjusting for age, sex, race, income, and BMI. We then used an optimization approach to compile a weighted sum of the quartile scores, both within and across chemical classes. Using the optimization approach to construct weighted quartile scores, the dioxin like PCB, the non-dioxin like PCB and metal class-level scores were significantly associated with elevated ALT. A significant interaction was detected between the class-level score for metals, and the score for non-dioxin-like PCBs. When including all chemicals in one model, 3 chemicals accounted for 78% of the weight (mercury, PCB 180, 3,3',4,4',5-PNCB) with the remaining 22% associated with 4 chemicals (a dioxin and 3 PCBs). Validation with a holdout dataset indicated that the weighted quartile sum estimator efficiently identifies reproducible significant associations., (Published by Elsevier GmbH.)