Low-level HIV viraemia during antiretroviral therapy: Longitudinal patterns and predictors of viral suppression.

OBJECTIVES: Our objective was to characterize longitudinal patterns of viraemia and factors associated with viral suppression in people with HIV and low-level viraemia (LLV) during antiretroviral therapy (ART). METHODS: We included people with HIV in the EuResist Integrated Database with LLV following ART initiation after 2005. LLV was defined as two or more consecutive viral load (VL) measurements of 51-199 copies/mL 30-365 days apart after >12 months of ART. Viraemia patterns were analyzed over 24 months. Factors associated with viral suppression at 12 months after LLV episodes were identified using univariable and multivariable logistic regression. RESULTS: Of 25 113 people with HIV, 2474 (9.9%) had LLV. Among 1387 participants with 24 months of follow-up after LLV, 406 (29%) had persistent suppression, 669 (48%) had transient viraemic episodes, 29 (2%) had persistent LLV, and 283 (20%) had virological failure. Following LLV episodes, the proportion with detectable viraemia declined (p for trend <0.001 and 0.034, in the first and second year, respectively). At 12 months, 68% had undetectable VL, which was associated with suppression before LLV (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.2-2.4) and ART modification after LLV (aOR 1.6; 95% CI 1.0-2.4). The following factors were negatively associated with undetectable VL at 12 months: higher VL during LLV (aOR 0.57 per log10 copies/mL; 95% CI 0.37-0.89), injecting drug use (aOR 0.67; 95% CI 0.47-0.96), and regimens with protease inhibitors (aOR 0.65; 95% CI 0.49-0.87) or combined anchor drugs (aOR 0.52; 95% CI 0.32-0.85). CONCLUSION: Most people with LLV did not experience sustained viral suppression during 24-month follow-up, supporting the association between LLV and inferior treatment outcome.

Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients.

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.

[Neuroendorine paraneoplastic syndromes]. / Neuroendokrine paraneoplastische Syndrome.

Skin is commonly affected by neuroendorine paraneoplastic syndromes (PNS). This is due to the expression of receptors in the skin by which abnormally secreted neuroendocrine hormones and mediators elicit directly, and indirectly, cutaneous key signs and thus facilitate early diagnosis of these diseases. In acromegaly, induction of the growth hormone-insulin-like growth factor­1 axis results in trophic changes of the acral portions of the skin and mucosal membranes including cutis verticis gyrata. The skin signs of non-iatrogenic Cushing syndrome are identical with those of exogenous prolonged intake of glucocorticoids: centripetal accumulation of adipose tissue, plethora and striae distensae. Episodic flushing of the face and trunk (together with explosive diarrhea) is a key feature of carcinoid tumors. Fibrotic remodeling of the heart and retroperitoneal space, and less commonly of the skin, are important complications mediated by abnormally secreted 5­hydroxytryptamine (serotonin, 5­HT), the latter eliciting profibrotic responses on HT2B-receptor-expressing fibroblasts. Androgen-secreting tumors lead to well-established receptor-mediated cutaneous signs of peripheral hyperandrogenisms: seborrhea, acne, hirsutism, and androgenetic alopecia. In contrast, the pathogenesis of necrolytic migratory erythema as a key feature of glucagonoma remains incompletely understood and is thought to be related to hypoaminoacidemia. This review summarizes the clinical features of neuroendocrine PNS with skin involvement, elucidates its underlying pathophysiology, lists differential diagnoses, and explains key diagnostic steps and principal therapeutic options. An interdisciplinary approach is essential to provide the best care of all patients with neuroendocrine PNS.

Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study.

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

[Update on heart failure]. / Neues zur Herzinsuffizienz.

Heart failure is one of the leading diseases in internal medicine worldwide. Because of the increase in population aging, the incidence and prevalence of heart insufficiency is rising annually and is now the most frequent individual diagnosis among hospitalized patients in Germany. The mortality rate has recently been reduced, since new pharmacological options, especially the inhibition of neprilysin, have been developed; however, heart failure is still associated with a high mortality and morbidity rate. Thus, guideline-conform treatment is of crucial importance. This review highlights and summarizes the current scientific knowledge on heart failure from 2017 and 2018 based on the guidelines of the European Society of Cardiology. New aspects about heart failure with middle grade limitations of ejection fraction are firstly presented. Subsequently, innovative diagnostic and therapeutic strategies, new pharmacological developments and handling of frequent comorbidities in patients with heart failure are discussed.

[Evidence-based drug therapy for heart failure-an update]. / Aktuelles zur evidenzbasierten medikamentösen Herzinsuffizienztherapie.

Chronic heart failure affects millions of people worldwide and is associated with high morbidity and mortality. Because of steadily increasing ageing populations and improved survival rates after myocardial infarction, the incidence of chronic heart failure is rising. As acute decompensated heart failure is one of the leading causes for hospitalization in Germany, heart failure imposes a huge economic burden on its health care system. Guideline directed therapy is important to improve prognosis. In the following, we give an overview about novel heart failure clinical trial results and point to important comorbidities.

[Cognitive dysfunction in heart failure-Causes and sequelae]. / Kognitive Dysfunktion bei Herzinsuffizienz ­ Ursachen und Folgen.

Approximately 40% of patients with heart failure show cognitive deficits, such as concentration difficulties, attention deficits, and memory impairment. Affected patients have a higher rate of rehospitalization and an increased mortality. This could be due to low adherence mediated by a lack of disease-specific knowledge and strategies to deal with symptom exacerbation. The pathogenesis of cognitive deficits in heart failure is multifactorial. In this respect the heart failure itself as well as cardiovascular risk factors and comorbidities play a role. Orientating neuropsychological screening tests can show a first indication of the presence of cognitive impairment. When identified, the causes can be specifically treated and care can be optimized through certain measures, such as the involvement of caregivers and healthcare providers.

[Valvular heart disease in patients with chronic kidney disease]. / Herzklappenvitien bei chronischer Niereninsuffizienz.

Valvular heart disease is a common comorbidity in patients with impaired renal function, especially in those with end-stage renal disease undergoing dialysis. Sclerosis and calcification of the heart valves and the valve ring are particularly relevant in the etiology of the diseases. These typically occur at the aortic and mitral valves and can lead to both insufficiency and stenosis of the affected valve. In the current guidelines of the European Society for Cardiology published in 2017, surgical treatment remains the standard of care for most forms of severe valvular heart disease; however, the presence of chronic kidney disease impairs clinical outcomes and is associated with higher mortality rates when compared to patients with preserved renal function. Catheter-based treatment options have emerged as an effective and safe alternative for patients >75 years and/or with increased surgical risk. Consequently, in patients with appropriate anatomy and elevated risk, interventional treatment options should also be discussed in the heart team.

Protection of glucotoxicity by a tripeptide derivative of α-melanocyte-stimulating hormone in human epidermal keratinocytes.

BACKGROUND: Chronic skin ulcers are a major complication and a therapeutic challenge in patients with diabetes mellitus. Glucose-induced accumulation of reactive oxygen species (ROS) is considered to be an important pathogenetic factor in diabetes. OBJECTIVES: To characterize the impact of high glucose (HG) on normal human keratinocytes (NHKs) and examine if Lys-d-Pro-Thr (KdPT), a tripeptide derived from α-melanocyte-stimulating-hormone, has protective effects. METHODS: We investigated the key functions of NHKs under HG conditions with or without KdPT in vitro as well as ex vivo employing a skin organ culture model. RESULTS: HG impaired metabolic activity, cell proliferation, viability and migration of NHKs. As shown by atomic force microscopy HG altered the biophysical properties of NHKs, i.e. cell size and elasticity. Glucotoxicity in NHKs was paralleled by the induction of intracellular ROS and endoplasmic reticulum stress. KdPT attenuated HG-induced oxidative stress and antagonized the effects of glucose on cell viability, metabolic activity and migration. Importantly, KdPT also antagonized the suppressive effect of HG on epidermal migration in wounded human skin organ cultures. CONCLUSIONS: Our findings highlight a novel effect of KdPT that could be exploited for the future therapy of diabetic skin ulcers.

[Blood pressure targets in patients with diabetes mellitus : What are optimum values?] / Blutdruckziele bei Patienten mit Diabetes mellitus : Was sind optimale Werte?

Diabetes mellitus and arterial hypertension are the most prevalent diseases in the aging population. Both are important risk factors for the development of cardiovascular complications and are associated with a high mortality. Both diseases are often first recognized late. The prognosis of patients with diabetes mellitus is favorably influenced by an optimal adjustment of blood sugar and blood pressure, as confirmed in large randomized clinical trials. Patients with diabetes mellitus and a blood pressure >130/80 mm Hg should first receive life style counseling with respect to nutrition and activity. Drug treatment for reduction of blood pressure is recommended for a blood pressure ≥140/90 mm Hg.

[Cardiovascular pharmacotherapy and coronary revascularization in end-stage renal failure]. / Kardiovaskuläre Pharmakotherapie und koronare Revaskularisation bei terminaler Niereninsuffizienz.

There is a close physiological relationship between the kidneys and the heart. Cardiovascular diseases are the most prevalent cause of death in patients with chronic kidney disease (CKD), whereas CKD may directly accelerate the progression of cardiovascular diseases and is considered to be a cardiovascular risk factor. In patients with mild CKD, i.e. an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2, treatment of coronary artery disease and chronic heart failure is not essentially different from patients with preserved renal function; however, as most pivotal trials have systematically excluded patients with advanced renal failure, many treatment recommendations in this patient group are based on observational studies, post hoc subgroup analyses and meta-analyses or pathophysiological considerations, which are not supported by controlled studies. Therefore, prospective randomized studies on the management of heart failure and coronary artery disease are needed, which should specifically focus on the growing number of patients with advanced renal functional impairment.

[Comments on the guidelines (2018) of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension]. / Kommentar zu den Leitlinien (2018) der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Gesellschaft für Hypertonie (ESH) für das Management der arteriellen Hypertonie.

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.

Most children with eosinophilic esophagitis have a favorable outcome as young adults.

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85-21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare.

Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PURPOSE: We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. MATERIALS AND METHODS: A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. RESULTS: Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). CONCLUSIONS: In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry.

BACKGROUND: Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. METHODS: Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. RESULTS: In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. CONCLUSION: Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.

[Traumatic Lacrimal Duct Stenosis: Demographics and Success Rate of Surgical Procedures for Secondary Treatment]. / Traumatische Tränenwegsstenosen: Epidemiologie und Erfolgsraten nach sekundärer operativer Intervention.

BACKGROUND: Traumatic lacrimal duct stenosis can be the result of sharp trauma of the eyelid, indirect trauma or surgery in the nasoorbital region, as well as burns, chemotherapy and radiation of the facial region. The aim of the study is to present the demographics, patient satisfaction, and course of different surgical procedures for secondary treatment of traumatic lacrimal duct stenosis. METHODS: We retrospectively reviewed the medical records of 50 patients who required surgery for traumatic lacrimal duct stenosis from 2009 to 2011 at the University Eye Hospital in Muenster. The evaluation included the following criteria: age, sex, duration of symptoms, complication rate and the rate of recurrence. We systematically evaluated the medical data and asked the patients about the recent symptoms via telephone questionnaire. RESULTS: 60 eyes of 50 patients were included (18 women; 32 men; age: 51.8 ± 17.1 years); 34 eyes (56.7 %) had already had operations of the lacrimal system. The success rate was 58.1 %. The mean postoperative follow-up was 52.3 ± 10.7 months. In 11 cases (18.3 %), a dakryocystorhinostomy (DCR) was necessary. CONCLUSION: Traumatic lacrimal stenosis is more common in men, and has a poorer prognosis than lacrimal duct stenosis from other causes.

Low resting heart rates are associated with new-onset atrial fibrillation in patients with vascular disease: results of the ONTARGET/TRANSCEND studies.

BACKGROUND: Elevated systolic blood pressure (SBP) and high resting heart rate (HR) are associated with cardiovascular end-points. Although the association between atrial fibrillation (AF) and SBP is well established, the relation between AF and HR remains unclear. METHODS: In patients from the ONTARGET and TRANSCEND studies with high cardiovascular disease risk (n = 27 064), new-onset AF was evaluated in relation to mean SBP, visit-to-visit variation in SBP (SBP-CV; i.e. SD/mean × 100%), mean HR and visit-to-visit variation in HR (HR-CV). RESULTS: Low mean HR (P < 0.0001) and high SBP (P = 0.0021) were associated with incident AF. High SBP-CV (P = 0.031) and HR-CV (P < 0.0001) were also associated with incident AF. After adjustment for confounders, SBP and SBP-CV were no longer significantly associated with AF. The detrimental effect of low HR was particularly evident in subjects who were not receiving treatment with beta-blockers (P = 0.014 for interaction between beta-blocker use and mean HR). In addition to low HR, high HR-CV and high SBP had additive effects on incident AF. CONCLUSIONS: Low mean HR (<60 beats min(-1) ) is independently associated with incident AF, and low HR-CV and high SBP further increase the incidence of new-onset AF in patients at high risk of cardiovascular disease.

Resting heart rate is associated with renal disease outcomes in patients with vascular disease: results of the ONTARGET and TRANSCEND studies.

BACKGROUND: Resting heart rate (RHR) is associated with cardiovascular disease outcomes in high-risk patients. It is not known whether RHR is predictive of renal outcomes such as albuminuria, end-stage renal disease (ESRD) or doubling of creatinine. We evaluated whether RHR could predict renal endpoints in patients at a high risk of cardiovascular disease. We also tested the effects of RHR at different levels of systolic blood pressure (SBP). METHODS: We analysed data from 28 757 patients in the ONTARGET and TRANSCEND trials. RHR and SBP were available for a mean of 4.9 ± 0.4 visits (range 3-5) within the first 2 years of the studies. Albuminuria was determined at baseline, at 2 years and at study end. RESULTS: Mean RHR was predictive of incident micro-albuminuria [hazard ratio (HR) for RHR ≥80 vs. <60 beats min(-1) 1.49, 95% confidence interval (CI) 1.29-1.71, P < 0.0001], incident macro-albuminuria (HR 1.84, 95% CI 1.39-2.42, P < 0.0001), doubling of creatinine (HR 1.47, 95% CI 1.00-2.17, P = 0.050) and ESRD (HR 1.78, 95% CI 1.00-3.16, P = 0.050), and the combined renal end-point (HR 1.51, 95% CI 1.32-1.74, P < 0.0001). Associations were robust at SBPs from <120 to ≥150 mmHg, with the lowest risk at a SBP of 130-140 mmHg. CONCLUSION: Resting heart rate is a potent predictor of these renal outcomes, as well as their combination, in patients with cardiovascular disease. RHR at all SBP levels should be considered as a possible renal disease risk predictor and should be investigated as a treatment target with RHR-reducing agents.