Ventricular-arterial coupling (VAC) in a population-based cohort of middle-aged individuals: The STANISLAS cohort.

BACKGROUND AND AIMS: Data exploring normal values of different ventricular-arterial coupling (VAC) parameters and their association with anthropometric and cardiovascular (CV) factors are scarce. We aim to report values of two different methods of VAC assessment according to age and sex and explore their association with CV factors within a large population-based cohort of middle-aged individuals. METHODS: For 1333 (mean age 48 ± 14) individuals participating in the 4th visit of the STANISLAS cohort, VAC was assessed by two methods [1]: arterial elastance (Ea)/end-systolic elastance (Ees) and [2] Pulse wave velocity (PWV)/Global longitudinal strain (GLS). RESULTS: The mean values of Ea/Ees and PWV/GLS were 1.06 ± 0.20 and 0.42 ± 0.12, respectively. The two methods of VAC assessment were poorly correlated (Pearson's correlation coefficient r = 0.14 (0.08; 0.19)). Increased PWV/GLS was associated with older age and a higher degree of cardiovascular risk factors (i.e., BMI, blood pressure, LDL, diabetes, hypertension) in the whole population as well as in the parent generation. In contrast, higher Ea/Ees were associated with decreasing age, and lower prevalence of risk factors in the whole cohort but neutrally associated with risk factors in the parent generation. CONCLUSIONS: Higher PWV/GLS is significantly associated with CV factors regardless of age. In contrast, worse Ea/Ees is associated with a better CV risk profile when considering individuals aged 30 to 70 but neutrally associated with CV factors when considering only older patients. These results may suggest that PWV/GLS should preferably be used to explore VAC. In addition, age-individualized threshold of Ea/Ees should be used.

Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.

Pragmatic diagnostic and therapeutic algorithms to optimize new potassium binder use in cardiorenal disease.

BACKGROUND: Pivotal randomized trials demonstrating efficacy, safety and good tolerance, of two new potassium binders (patiromer and sodium zirconium cyclosilicate) led to their recent approval. A major hurdle to the implementation of these potassium-binders is understanding how to integrate them safely and effectively into the long-term management of cardiovascular and kidney disease patients using renin angiotensin aldosterone system inhibitors (RAASi), the latter being prone to induce hyperkalaemia. METHODS: A multidisciplinary academic panel including nephrologists and cardiologists was convened to develop consensus therapeutic algorithm(s) aimed at optimizing the use of the two novel potassium binders (patiromer and sodium zirconium cyclosilicate) in stable adults who require treatment with RAASi and experience(d) hyperkalaemia in a non-emergent setting. RESULTS: Two dedicated pragmatic algorithms are proposed. The lowest intervention threshold (i.e. 5.1 mmol/L or greater) was the one used in the patiromer and sodium zirconium cyclosilicate) pivotal trials, both drugs being indicated to treat hyperkalaemia in a non -emergent setting. Acknowledging the heterogeneity across specialty guidelines in hyperkalaemia definition and thresholds to intervene when facing hyperkalaemia, we have been mindful to use soft language i.e. "it is to consider", not necessarily "to do". CONCLUSIONS: Providing the clinical community with pragmatic algorithms may help optimize the management of high-risk patients by avoiding the risks of both hyper and hypokalaemia and of suboptimal RAASi therapy.

NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients.

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Low N-terminal pro-brain natriuretic peptide levels are associated with non-alcoholic fatty liver disease in patients with type 2 diabetes.

AIM: Natriuretic peptides (NPs) have emerged as important regulators of lipid metabolism. Reduced levels of NPs are reported in obesity and in patients with type 2 diabetes (T2D). This NP deficiency may affect their ectopic fat distribution and lead to high risk of non-alcoholic fatty liver disease (NAFLD). METHODS: In this cross-sectional study, the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and liver fat content was quantified using 1H-magnetic resonance spectroscopy in 120 patients with T2D. RESULTS: NAFLD (defined as liver fat content ≥ 5.6%) was found in 57 (48%) of the T2D patients, who also had significantly lower NT-proBNP (P = 0.002) levels compared with patients without NAFLD, but did not differ as regards the presence of cardiovascular disease (CVD) or in kidney function. After adjusting for potential confounders (age, gender, HbA1c, BMI, HOMA2-IR, CVD, eGFR), the odds ratio for the presence of NAFLD was increased by 2.9 (P = 0.048) for NT-proBNP levels < 45 ng/L. In a multivariable linear regression model, the relationship with NT-proBNP was further analyzed as a continuous variable, and was independently and inversely associated with increasing liver fat content after full adjustment (P = 0.031). CONCLUSION: Reduced plasma NT-proBNP levels are independently associated with high liver fat content in patients with T2D. The present study suggests that NP deficiency may play a role in the development of NAFLD in T2D.

Evaluation of Subclinical Fluid Overload Using Lung Ultrasound and Estimated Plasma Volume in the Postoperative Period Following Kidney Transplantation.

AIM: B-lines count measured with lung ultrasound (LUS) quantifies extravascular lung water and is validated in the setting of acute cardiac failure or chronic dialysis. Patients are often kept in moderately overhydrated states during the early postoperative period following kidney transplantation (KT). We described congestion changes during the early postoperative period following KT and the feasibility of LUS in this setting. METHODS: LUS (28 scanning-points method) and inferior vena cava (IVC) measurements were routinely performed in 36 patients after KT. Estimated plasma volume (ePV) was calculated from hemoglobin and hematocrit levels. RESULTS: No patient had >15 B-lines during the hospital stay. B-lines slightly increased until Day 4 after KT (Day 1, 1.7 ± 1.7; Day 4, 2.5 ± 2.5) and decreased up to Day 10 (1.4 ± 2.2; P vs Day 4 <.05). More B-lines were observed in patients aged older than 60 (P = .01 at Day 4) whereas IVC diameter and ePV were similar. In patients older than 60, B-lines had weak correlation with body weight variation (r = 0.64; P < .05), IVC diameters (r = 0.59 at Day 4 and r = 0.58 at Day 10; P < .05) but a strong correlation with ePV (r = 0.93 at Day 14; P < .05). B-line changes from Day 1 to Day 10 correlated with IVC diameter changes (r = 0.62; P < .05). CONCLUSION: LUS identifies subtle congestion changes during the early postoperative period following KT. The hyperhydration strategy usually followed during this period does not result in overt pulmonary congestion as assessed by LUS, even in older recipients.

Impact of Hyperkalemia and Worsening Renal Function on the Use of Renin Angiotensin Aldosterone System Inhibitors in Chronic Heart Failure With Reduced Ejection Fraction.

Patients with heart failure (HF) and reduced ejection fraction (HFREF) are at increased risk of death and hospitalizations for HF. Numerous registries have reported a large and persistent gap between real-life practice in the use of life-saving evidence-based therapies, such as renin angiotensin system inhibitors, beta blockers, mineralocorticoid receptor antagonists (MRAs), and recommended practices in international guidelines. The fears of inducing hyperkalemia and/or worsening renal function are the main triggers of this underuse.

Combined baseline and one-month changes in big endothelin-1 and brain natriuretic peptide plasma concentrations predict clinical outcomes in patients with left ventricular dysfunction after acute myocardial infarction: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

OBJECTIVE: Increased levels of neuro-hormonal biomarkers predict poor prognosis in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD). The predictive value of repeated (one-month interval) brain natriuretic peptides (BNP) and big-endothelin 1 (BigET-1) measurements were investigated in patients with LVSD after AMI. METHODS: In a sub-study of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS trial), BNP and BigET-1 were measured at baseline and at 1month in 476 patients. RESULTS: When included in the same Cox regression model, baseline BNP (p=0.0003) and BigET-1 (p=0.026) as well as the relative changes (after 1month) from baseline in BNP (p=0.049) and BigET-1 (p=0.045) were predictive of the composite of cardiovascular death or hospitalization for worsening heart failure. Adding baseline and changes in BigET-1 to baseline and changes in BNP led to a significant increase in prognostic reclassification as assessed by integrated discrimination improvement index (5.0%, p=0.01 for the primary endpoint). CONCLUSIONS: Both increased baseline and changes after one month in BigET-1 concentrations were shown to be associated with adverse clinical outcomes, independently from BNP baseline levels and one month changes, in patients after recent AMI complicated with LVSD. This novel result may be of clinical interest since such combined biomarker assessment could improve risk stratification and open new avenues for biomarker-guided targeted therapies. KEY MESSAGES: In the present study, we report for the first time in a population of patients with reduced LVEF after AMI and signs or symptoms of congestive HF, that increased baseline values of BNP and BigET-1 as well as a further rise of these markers over the first month after AMI, were independently predictive of future cardiovascular events. This approach may therefore be of clinical interest with the potential of improving risk stratification after AMI with reduced LVEF while further opening new avenues for biomarker-guided targeted therapies.

Interactions cardiorénales.

Hypertension is common in patients with chronic renal disease particularly those with diabetes. It is sometimes resistant to the pharmacological treatment. The mineralocorticoid receptor antagonist spironolactone may be indicated here. The mineralocorticoid receptor antagonists have a Class 1, Level A indication for the treatment of heart failure with reduced ejection fraction. There is an associated risk of worsening renal function and of hyperkalemia which does not hinder their clinical benefit. However, an appropriate biological monitoring is warranted, along with potential dose adaptations. Cardiorenal syndrome significantly worses the prognosis of congestive heart failure. The use of ultrafiltration can be effective when conventional treatments failed. Its place in the front line needs to be evaluated.

Temporal Trend and Time-Varying Effect of Preemptive Second Kidney Transplantation on Graft Survival: A 30-Year Single-Center Cohort Study.

BACKGROUND: There are discrepancies regarding the impact of preemptive 2nd kidney transplantation (PSKT) on graft survival. The present study aimed to determine whether the association between PSKT and outcome varies over time and whether this association is era dependent. METHODS: A total of 266 patients underwent SKT (244 non-PSKT, 22 PSKT) in our center from 1985 to 2015. Association between PSKT and graft survival (allograft failure from any cause including death) was assessed with the use of Cox models. RESULTS: During a median follow-up of 6.7 years, 116 events were recorded: 72 returns to dialysis and 44 deaths before return to dialysis. Survival curves diverged up to 5 years (5-year survivals: PSKT, 94.1 ± 5.7%; non-PSKT, 76.8 ± 2.9%) but they converged thereafter (12-year survivals: PSKT, 50.9 ± 15.2%; non-PSKT, 55.5 ± 3.9%). After adjustment for age and living-donor status, PSKT tended to be associated with better graft survival (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.02-1.27; P = .08) within the first 5 years of SKT but tended to be associated with worse outcome thereafter (HR, 2.36; 95% CI, 0.97-5.72; P = .06; P for interaction with time = .04). In addition, a significant interaction was identified between PSKT and SKT year (P for interaction = .04). In the multivariable model, the estimated HR for PSKT was 2.54 (95% CI, 0.88-7.35; P = .08) in 1990 as opposed to 0.16 (95% CI, 0.02-1.17; P = .07) in 2012. CONCLUSIONS: The effect of PSKT on graft survival varies over time and according to year of the procedure. Although the benefit observed within the first 5 years of SKT appears to fade over time, overall graft survival seemingly improved in more recent years.

Neural modulation for hypertension and heart failure.

Hypertension (HTN) and heart failure (HF) have a significant global impact on health, and lead to increased morbidity and mortality. Despite recent advances in pharmacologic and device therapy for these conditions, there is a need for additional treatment modalities. Patients with sub-optimally treated HTN have increased risk for stroke, renal failure and heart failure. The outcome of HF patients remains poor despite modern pharmacological therapy and with established device therapies such as CRT and ICDs. Therefore, the potential role of neuromodulation via renal denervation, baro-reflex modulation and vagal stimulation for the treatment of resistant HTN and HF is being explored. In this manuscript, we review current evidence for neuromodulation in relation to established drug and device therapies and how these therapies may be synergistic in achieving therapy goals in patients with treatment resistant HTN and heart failure. We describe lessons learned from recent neuromodulation trials and outline strategies to improve the potential for success in future trials. This review is based on discussions between scientists, clinical trialists, and regulatory representatives at the 11th annual CardioVascular Clinical Trialist Forum in Washington, DC on December 5-7, 2014.

Galectin-3 inhibition prevents adipose tissue remodelling in obesity.

Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg(-1) per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10(-8 )m) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity.

Review of heart failure treatment in type 2 diabetes patients: It's at least as effective as in non-diabetic patients!

Our society is currently facing an epidemic of diabetes and heart failure. Historically, certain cardiology treatments, mainly beta-blockers, have been considered 'dangerous' in diabetic patients, but the time has come for personalized medicine to be applied in the field of cardiology, especially in heart failure (HF). To determine whether HF treatment should be individualized according to diabetes status, this review of the available randomized evidence was carried out, with special emphasis on treatment-effect modification in relation to diabetes. Based on a large body of evidence in the literature, our review concludes that HF treatment should be the same for diabetic and non-diabetic patients. In concurrence, international guidelines now strongly advocate the use of HF drugs, including beta-blockers, in diabetic HF patients. The benefit of HF treatment is at least as favourable in such patients as in non-diabetic patients on a relative basis. Given the higher risk of events in diabetics, this could translate to an even greater absolute impact of HF treatment in these patients, which should further encourage caregivers to more aggressively manage HF in diabetic patients. To this end, non-cardiologists, including general practitioners and endocrinologists/diabetologists who treat diabetic HF patients, should be considered part of the HF drug optimalization process, including the referral of patients to specialized centres for possible implantable cardiac defibrillators and/or cardiac resynchronization indication assessment.

Increased visit-to-visit blood pressure variability is associated with worse cardiovascular outcomes in low ejection fraction heart failure patients: Insights from the HEAAL study.

BACKGROUND: Recent data have highlighted shortcomings of the usual blood pressure (BP) hypothesis in several populations, and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. Herein, we aimed at assessing the association between visit-to-visit BP variability and outcomes in chronic heart failure (CHF) patients enrolled in the Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL). METHODS AND RESULTS: The HEAAL study randomized 3834 patients with HF and reduced ejection fraction administered 150 mg or 50mg losartan daily in a double blind, randomized, controlled trial. The patients were followed up for up to 6.8 years after randomization, and BP was measured at 3 time points in the first year and at semi-annual visits in the years thereafter. Three measures of visit-to-visit BP variability were computed for each subject: the standard deviation, the coefficient of variation and the average absolute visit-to-visit variation. Cox proportional hazard models were used to investigate the relationship between variations in systolic blood pressure, baseline covariates and the time to death or heart failure hospitalization (i.e. primary outcome). In multivariate analyses stratified on baseline BP, the patients with higher visit-to visit BP variability exhibited poorer outcomes (average absolute difference in SBP in mmHg:hazard ratio: 1.023 [95% CI (1.013, 1.034), P<0.0001]), independent from high dose losartan (still beneficial). CONCLUSIONS: For the first time, visit-to-visit BP variability was found elevated in CHF patients with reduced ejection fraction, and associated with poorer cardiovascular outcomes. Such assessments should be prioritized for testing prevention strategies in CHF. CLINICAL TRIAL REGISTRATION: This study is registered with the ClinicalTrials.gov, number NCT00090259.

Incident hyperkalemia may be an independent therapeutic target in low ejection fraction heart failure patients: insights from the HEAAL study.

BACKGROUND: Angiotensin receptor antagonists (ARBs) improve outcomes in patients with heart failure (HF) with reduced left ventricular ejection fraction, but may induce hyperkalemia (HK) and/or a worsening of renal function (WRF). METHODS AND RESULTS: The incidence and risk factors of HK and its inter-relationship with WRF, as well as associations with clinical outcome (death or admission for HF i.e. the primary outcome) in 3846 HF patients enrolled in the double blind HEAAL trial (losartan 150 mg/d vs. 50 mg/d) were assessed. Worsening of renal function was defined as a decrease in eGFR >20% from baseline and HK as serum K >5.5 or >5 mmol/L. Higher dose of losartan increased serum potassium. Episodes of HK >5 mmol/L or WRF occurred at least once in about half of the patients. WRF was associated with higher occurrence of HK (HR 1.19 (1.06-1.34)) and vice versa (HR 1.35 (1.19-1.53)), but preceded HK in only about half of the events. High dose losartan improved outcome despite more frequent WRF and HK, both being independently associated with adverse outcomes in multivariate analyses. CONCLUSIONS: HK and WRF are common in HF patients. Both can be predicted from baseline risk factors and are therefore potentially preventable. Although associated with worse outcome, occurrence of any does not hinder the efficacy of high dose losartan. HK was associated with WRF and worse outcomes. Whether therapy targeting specifically HK may maximize the survival benefit derived from renin angiotensin aldosterone inhibitor use should be appropriately tested in future trials.

Salivary aldosterone as a diagnostic aid in primary aldosteronism.

Recent evidence demonstrates an increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population, making noninvasive and simple screening methods necessary. The aim of the present study was to apply a time-resolved fluorescence immunoassay for the measurement of aldosterone in saliva and the establishment of a cut-off to identify patients with a high likelihood for PA requiring subsequent screening with the aldosterone to renin ratio. Saliva was collected (AM and PM) to ascertain an optimum time with best discriminating power between healthy and disease states. Plasma aldosterone, after overnight recumbency and 4 h later, was collected for posture testing. The participants included 53 PA patients (aged 14-78), 54 with essential hypertension (EH, aged 19-82), and 38 healthy volunteers (aged 19-56). Saliva aldosterone (SA) (median, 25-75(th)%) in PA was found at 90 pg/ml (61-139) compared to 53 pg/ml (40-85) in EH, with discrimination between PA versus EHs best in the morning (cutoff: 81 pg/ml, 77% sensitivity, 82% specificity). Saliva aldosterone decreases throughout the day in patients with adenomas [APA AM: 123 pg/ml (92-213) vs. PM: 79 pg/ml (41-116)], but not in those with bilateral hyperplasia [BAH AM: 85 pg/ml (59-115)] vs. pm 69 pg/ml (57-114). Morning SA alone allows discrimination between PA and controls, though with significant overlap against EHs, leading to a high number of false positives. More promising is the use of diurnal variation in SA in distinguishing between APA and BAH. The decline in SA seen in patients with APA presents a more constant finding compared to posture testing, which fails to correctly classify a large number of patients.

Saliva as a medium for aldosterone measurement in repeated sampling studies.

BACKGROUND: Saliva is a readily available biological fluid, making it convenient in diagnosis of diseases and in multi-sampling protocols. Several salivary steroids give a useful index of free plasma levels. Increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population has increased interest in the mineralocorticoid aldosterone. METHODS: A biotinylated-aldosterone tracer and a commercially available antibody are used in a time-resolved fluorescence immunoassay (TR-FIA) to measure salivary aldosterone (SA). Saliva was collected in various multi-sampling protocols: Investigation of diurnal rhythm in healthy and PA patients, ACTH stimulation test and posture test in healthy subjects. RESULTS: Method validation showed a sensitivity of 19 ng/L and intra-/inter-assay precision between 7.2-10.1% and 8.7-15.7%, respectively. SA correlated significantly (y = 0.2995x +/- 0.01, r(2)=0.60) to plasma aldosterone measured by a commercial radioimmunoassay. SA (median; 95%CI) was at 111 (95-127)ng/L in PA (n=84) and 50 (44-56)ng/L in healthy subjects (n=60). After change in posture, aldosterone increased in both, saliva (57 (47-63)ng/L to 95 (84-117)ng/L) and plasma (26 (26-41)ng/L to 135 (110-181)ng/L). Peak levels were reached after 1h, and were higher in females than in males. CONCLUSIONS: SA correlates well to plasma aldosterone and mirrors responses during conditions of stress. SA is significantly higher in PA, and the diurnal rhythm seen in the healthy is blunted in PA. We additionally found gender-dependent differential responses to posture, with higher increases in females. Measurement of aldosterone in saliva presents a useful and convenient method for application in multi-sampling studies.

[Convulsions following dialysis sessions]. / Convulsions dans le décours de séances de dialyse.

A bipolar patient with renal angiosclerosis due to lithium intoxication showed convulsive crises for about four months after each haemodialysis session. Aetiological work up was not able to isolate a unique cause, but modifications in treatment relieved the symptoms.

Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques.

BACKGROUND: Apoptosis of vascular cells is considered to be a major determinant of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be generated in atherosclerotic plaques and recent in vitro data suggest that plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis. AIM: To determine whether plasminogen activation may induce aortic VSMC apoptosis ex vivo and in vivo. METHODS AND RESULTS: Mice with single or combined deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1 (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica media from PAI-1-deficient mice induced plasminogen activation and VSMC apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin, active caspase 3 and VSMC apoptotic index were significantly higher in atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than in those from littermates with single ApoE deficiency. A parallel decrease in VSMC density was observed. CONCLUSIONS: These data strongly suggest that plasminogen activation may contribute to VSMC apoptosis in atherosclerotic plaques.

Estimating the total energy demand for supra-maximal exercise using the VO2-power regression from an incremental exercise test.

The VO2-power regression and estimated total energy demand for a 6-minute supra-maximal exercise test was predicted from a continuous incremental exercise test. Sub-maximal VO2-power co-ordinates were established from the last 40 seconds (s) of 150-second exercise stages. The precision of the estimated total energy demand was determined using the 95% confidence interval (95% CI) of the estimated total energy demand. The linearity of the individual VO2-power regression equations was determined using Pearson's correlation coefficient. The mean 95% CI of the estimated total energy demand was 5.9 +/- 2.5 mL O2 Eq x kg(-1) x min(-1), and the mean correlation coefficient was 0.9942 +/- 0.0042. The current study contends that the sub-maximal VO2-power co-ordinates from a continuous incremental exercise test can be used to estimate supra-maximal energy demand without compromising the precision of the accumulated oxygen deficit (AOD) method.