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Background: Pressure wave reflections (PWRs) within the circulation are assessed at various arterial sites by various noninvasive methods. We aimed at reviewing the conflicting data regarding the hypothesis that higher PWRs are associated with higher left ventricular mass and tested whether this association stands for all available indices of PWRs, all (proximal or distal to the heart) sites of assessment, and is modified by sex, age and heart rate. Methods: Based on a predefined protocol applying the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we identified eligible for meta-analysis data regarding: augmentation index, augmentation pressure, backward pressure (Pb), reflection index, and their association with left ventricular mass index (19 studies, total population n=8686). Results: We found statistically significant associations, independent from blood pressure level, for all indices of PWRs at all arterial sites (carotid augmentation index; odds ratio; standardized beta coefficient [β]: 0.14 [95% CI, 0.07% to 0.21%], per SD increase), radial augmentation index (β: 0.21; 0.11 to 0.31), central augmentation pressure (β: 0.15; 0.03 to 0.27), central Pb (β: 0.23; 0.05 to 0.42), and central reflection index (β: 0.14; 0.06 to 0.22), except for aortic augmentation index as estimated by generalized transfer functions. Meta-regression analysis showed that the association between carotid augmentation index and left ventricular mass was higher among populations with higher heart rate ( P =0.036, beta: 0.017 [95% CI, 0.001 to 0.033]) and tended to be higher in middle-aged ( P =0.07, beta: −0.001; −0.021 to 0.001). Conclusions: A clinically meaningful association between PWRs and left ventricular mass, assessed at either central or peripheral arterial sites by most available methods was shown, suggesting that PWR reduction strategies might be useful. Based on the present evidence, such trials should target middle-aged populations with high normal heart rate.

Introduction. The association of autoimmune thyroid disease (AITD) with diabetes mellitus type-1 (DM1) has been previously documented. However, limited data exist regarding the association of AITD and diabetes mellitus type-2 (DM2). The objective of the study was to expose the role of AITD on DM2 and the impact of AITD in euthyroid patients with pre-diabetes. Euthyroid prediabetic patients were defined by impaired fasting glucose and/or glucose intolerance. Material and methods. We assessed static and dynamic insulin resistance (IRI) and insulin secretion indices (ISI), and the disposition index (DI). Results. Out of 166 patients studied, 31.9% had AITD; impaired fasting glucose (IFG) prevalence was the same with non-AITD patients. In contrast, impaired glucose tolerance (IGT) was less prevalent in AITD compared to non-AITD patients (9.4% versus 28.3%, p=0.008). IRI did not differ between the two groups. The dynamic ISI, 1st phase and 2nd phase insulin release, and the DI showed a worse insulin secretion in non-AITD compared to AITD patients (0.54 versus 0.45, p=0.029; 1029.3 versus 864.3, p=0.033; 354.8 versus 286.5, p=0.035; 0.09 versus 0.07, p=0.02, respectively). On the other hand, hsCRP was higher in AITD versus non-AITD individuals (p=0.008). Conclusions. Although individuals with pre-diabetes and AITD presented with higher levels of low-grade inflammation, their dynamic ISI and the DI, were less impaired.

Aim To characterize different patterns of variability of three repeated within-visit blood pressure (BP) readings and to determine the prevalence of specific variation trends in systolic (SBP), diastolic (DBP) blood pressure and pulse pressure (PP). Methods Data from 53 737 subjects from the National Health and Nutrition Examination Survey were analyzed. In each subject, three consecutive BP measurements were performed with a minimum time-interval of at least 30 s. We propose three patterns of within-visit BP variability (separately for SBP, DBP and PP): (1) increasing trend (BP3 > BP2 > BP1); (2) decreasing trend (BP1 > BP2 > BP3) and (3) no trend (BP3 ≈ BP2 ≈ BP1). A threshold of minimum change (ΔP > 3 mmHg) between BP1-BP2 and BP2-BP3 was also applied as a prerequisite for the definition of these trends. Results An increasing trend was observed among three consecutive measurements of SBP, DBP and PP in 7.4, 10.4 and 10.2%, respectively. When a minimum threshold of 3 mmHg was set the respective increasing trends were observed in 1.8, 2.9 and 4.4%, respectively. There was a higher prevalence of decreasing trend within three consecutive SBP, DBP and PP readings: 17, 13.1 and 16.2%, respectively, whereas using a threshold of ΔP >3 mmHg the respective prevalence was 6.3, 4.1 and 7.7%. A maximum absolute difference >10 mmHg within triplicate of SBP/DBP/PP readings was observed in 12.9, 13 and 29.4%, respectively. In the era of personalized medicine, these patterns are well worth further investigation concerning their pathophysiologic and clinical relevance.

Non-invasive monitoring of cardiac output is a technological and clinical challenge, especially for critically ill, surgically operated, or intensive care unit patients. A brachial cuff-based, automated, oscillometric device used for blood pressure and arterial stiffness ambulatory monitoring (Mobil-O-Graph) provides a non-invasive estimation of cardiac output values simultaneously with regular blood pressure measurement. The aim of the study was to evaluate the feasibility of this apparatus to estimate cardiac output in intensive care unit patients and to compare the non-invasive estimated cardiac output values with the respective gold standard method of thermodilution during pulmonary artery catheterization. Repeated sequential measurements of cardiac output were performed, in random order, by thermodilution (reference) and Mobil-O-Graph (test), in 24 patients hospitalized at intensive care unit. Reproducibility and accuracy of the test device were evaluated by Bland–Altman analysis, intraclass correlation coefficient, and percentage error. Mobil-O-Graph underestimated significantly the cardiac output by −1.12 ± 1.38 L/min ( p 0.7 indicating a fair agreement between the test and the reference methods, while percentage error was approximately 39% which is considered to be within the acceptable limits. Cardiac output measurements were reproducible by both Mobil-O-Graph (intraclass correlation coefficient = 0.73 and percentage error = 27.9%) and thermodilution (intraclass correlation coefficient = 0.91 and percentage error = 26.7%). We showed for the first time that cardiac output estimation in intensive care unit patients using a non-invasive, automated, oscillometric, cuff-based apparatus is reproducible (by analyzing two repeated cardiac output measurements), exhibiting similar precision to thermodilution. However, the accuracy of Mobil-O-Graph (error compared to thermodilution) could be considered fairly acceptable. Future studies remain to further examine the reliability of this technology in monitoring cardiac output or stroke volume acute changes which is a more clinically relevant objective.

Wave reflection at central arteries consists of a major component of left ventricular afterload. Central augmentation index (AIx) is the most widely used surrogate of wave reflection. Recent technological developments now provide the ability to obtain, non‐invasively, aortic, or carotid pressure waves and measure AIx based on various algorithms of pulse wave analysis. The aim of this study was to compare AIx measurements performed by the Arteriograph, Complior, and Mobil‐O‐Graph apparatuses. Recordings by each device in randomized order were performed with 5‐minute interval at 211 individuals (age 55.1 ± 14.1 years, 67.8% males) who underwent diagnostic cardiovascular assessment. All measurements were obtained at the supine position, and AIx was calculated using the formula AIx = 100 × (Augmentation pressure)/(Pulse Pressure). Bland‐Altman analysis was performed. Mean difference (bias) ± one standard deviation of difference (with limits of agreement) of AIx between different devices was as follows: (a) Mobil‐O‐Graph vs Complior: −2.1 ± 14.8% (−31.1% to 26.9%), (b) Arteriograph vs Complior: 12.9 ± 14.6% (−15.7% to 41.5%), and (c) Mobil‐O‐Graph vs Arteriograph: −10.8 ± 16.9% (−43.9% to 22.3%). The three examined devices exerted significant differences in central AIx estimation which makes the three devices non‐interchangeable for wave reflection assessment. However, the Mobil‐O‐Graph device showed the highest agreement (lowest bias) with the Complior system as regards to the AIx measurement.

Progressive arterial stiffening, as a marker of arterial aging, may reach a plateau in elderly patients and may thus lose its clinical utility. This phenomenon may be more prominent in high-risk patients. We aimed to investigate if carotid-to-femoral pulse wave velocity (cf-PWV) is related to coronary artery disease (CAD) and diastolic dysfunction in elderly high-risk patients as compared to a control group of younger individuals.One-hundred and ninety-two high-risk stable patients who underwent coronary artery angiography and assessment of cf-PWV were consecutively recruited. Indices of diastolic dysfunction were also measured by echocardiography, including the volume of the left atrium and the ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (E').Increased cf-PWV was associated with the presence of CAD [odds ratio (OR) 1.34, P = 0.02], number of diseased coronary vessels (OR 1.17, P = 0.029) and CAD severity (P = 0.023) as assessed by Gensini score, in patients less than 65 years old after adjustment for traditional risk factors. Moreover, cf-PWV correlated with E/E' (P = 0.019) and increased the odds by 16% (OR 1.16, P = 0.048) for more severe diastolic dysfunction in patients aged below 65 years old. None of these outcomes correlated with cf-PWV in the elderly.In high cardiovascular risk patients, an age-dependent association of cf-PWV with CAD and diastolic dysfunction was evinced. In contrast to younger patients, these results suggest that measuring arterial stiffness in elderly high-risk patients may lack clinical value.

Therapy related acute myeloid leukemia (tAML) and secondary AML after an antecedent hematologic disorder (sAML-AHD) are often addressed together, blurring any clinical and prognostic differences. Among 516 AML patients, we compared characteristics and outcomes of 149 patients with “sAML” (sAML-AHD: 104, tAML: 45), uniformly and intensively treated during the last 2 decades at 1 center. Clinical outcomes of the whole “sAML” cohort were significantly inferior compared to de novo AML and in both intermediate and poor cytogenetic risk groups. Adverse karyotype had no effect on survival in tAML, while it was a negative predictor in sAML-AHD. Both groups showed similarly dismal outcome, with low complete remission rates (CR 44% vs. 41%) and median overall survival (OS 7 vs. 10.5 months). Allogeneic hematopoietic cell transplantation (alloHCT) recipients in CR1 had superior median OS (24 vs. 8 months). By multivariate analysis, alloHCT was an independent predictor of outcome, while karyotype was for sAML-AHD only. In conclusion, both “sAML” groups have inferior outcomes after chemotherapy, with adverse karyotype affecting primarily sAML-AHD. Until new treatment approaches are available, only alloHCT offers a survival advantage.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome, with long-term sequelae from birth to senescence. The long-term effects of PCOS are attributed to several metabolic aberrations ensuing the syndrome. In a systematic review of literature regarding the cardiovascular risk factors that accompany PCOS, we found that macrovascular function has been assessed by flow-mediated dilatation (FMD), microvascular function by venous occlusion plethysmography (VOP), and arterial structure by ultrasonographic assessment of intima-media thickness (IMT) usually of the carotid artery. Contradictory results have been reported; however, in most studies, endothelial dysfunction, an early marker of atherosclerosis assessed either by haemodynamic methods such as FMD or by biochemical methods such as endothelin-1 levels, was found to be impaired. VOP is a less-studied method, with few indices altered. IMT was found to be altered in most of the included studies, but the population was more heterogeneous. Inflammatory markers, including C-reactive protein, were also found to be altered in most studies. On the other hand, a number of interventions have been shown beneficial for the markers of cardiovascular risk, in the context of insulin-sensitizers. However, other interventions such as oral contraceptive pills or statins did not consistently show a similar beneficial effect. In summary, the early identification and eventual treatment of cardiovascular clinical and biochemical risk factors may be used in clinical practice to prevent potential ‘silent’ triggers of cardiovascular disease.

The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p0.001, and correlated significantly with procedural HITS (r = 0.5, p0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.

ObjectivesTo evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events, in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundThe impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during TAVR are unknown.MethodsPatients scheduled for TAVR were randomized prior to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 Reaction Units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions.ResultsAmong 90 patients randomized, six had inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p< 0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, and aortic valve calcium content, patients on ticagrelor had on average 255.9 (95% CI: [-335.4, -176.4]) fewer total procedural HITS, than did patients on clopidogrel. Platelet inhibition was greater in those randomized to ticagrelor 26 [10, 74.5] PRU than in those randomized to clopidogrel 207.5 [120-236.2] PRU, pConclusionsTicagrelor resulted in fewer procedural HITS, compared to clopidogrel, in patients undergoing TAVR, while achieving greater platelet inhibition, without increasing the risk for complications.Clinical Trial(ClinicalTrials.gov Identifier: NCT02989558)CONDENSED ABSTRACTWe conducted a two-center, prospective, open label, randomized, controlled clinical trial to compare the efficacy of ticagrelor vs clopidogrel in preventing cerebrovascular embolic events as assessed by transcranial Doppler during TAVR.The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) than in the clopidogrel group (723.5 [471.5, 875.0]), p< 0.001. Patients on ticagrelor had on average 255.9 (95% CI: [-335.4, -176.4]) fewer total procedural HITS than those on clopidogrel. This protective effect was not associated with an increase in complications.

Cardiac and aortic characteristics are crucial for cardiovascular disease detection. However, noninvasive estimation of aortic hemodynamics and cardiac contractility is still challenging. This paper investigated the potential of estimating aortic systolic pressure (aSBP), cardiac output (CO), and end-systolic elastance (Ees) from cuff-pressure and pulse wave velocity (PWV) using regression analysis. The importance of incorporating ejection fraction (EF) as additional input for estimating Ees was also assessed. The models, including Random Forest, Support Vector Regressor, Ridge, Gradient Boosting, were trained/validated using synthetic data (n = 4,018) from an in-silico model. When cuff-pressure and PWV were used as inputs, the normalized-RMSEs/correlations for aSBP, CO, and Ees (best-performing models) were 3.36 ± 0.74%/0.99, 7.60 ± 0.68%/0.96, and 16.96 ± 0.64%/0.37, respectively. Using EF as additional input for estimating Ees significantly improved the predictions (7.00 ± 0.78%/0.92). Results showed that the use of noninvasive pressure measurements allows estimating aSBP and CO with acceptable accuracy. In contrast, Ees cannot be predicted from pressure signals alone. Addition of the EF information greatly improves the estimated Ees. Accuracy of the model-derived aSBP compared to in-vivo aSBP (n = 783) was very satisfactory (5.26 ± 2.30%/0.97). Future in-vivo evaluation of CO and Ees estimations remains to be conducted. This novel methodology has potential to improve the noninvasive monitoring of aortic hemodynamics and cardiac contractility.

BACKGROUND There is increasing evidence that the method of calibration directly influences the association between brachial systolic blood pressure (bSBP) and estimated aortic systolic blood pressure (aSBP) and subsequently affects prognostic and diagnostic differentiation power of the latter. OBJECTIVE The aim of this study was to investigate associations between different methods of systolic pressure assessment in a large cohort and its comparison with recently published evidence. PARTICIPANTS AND METHODS During a public health campaign, cardiovascular hemodynamic data were assessed using a validated oscillometric device in a pharmacy setting. The device measures bSBP, mean arterial pressure, and diastolic blood pressure (DBP), and records brachial waveforms at the DBP level. aSBP1 was derived using bSBP and DBP and aSBP2 using measured mean arterial pressure and DBP for waveform calibration. In addition to pressures, age, sex, and anthropometric data were recorded. Regression analysis was carried out to investigate associations. RESULTS A total of 7409 (5133/2276, female/male) individuals with a median age of 54 years were sampled. aSBPs differed significantly from bSBP (126.0 mmHg) for aSBP1 (117.0 mmHg) and aSBP2 (127.5 mmHg, both P

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research.

Introduction Anti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD). Patients and Methods In our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors. Results Five-year overall survival (OS) was 46.9%, disease-free survival was 46.5%, and treatment-related mortality was 20.6%, with a median follow-up of 29 months (range, 1-145 months). Acute GVHD (grade ≥ II) cumulative incidence was 26.9% in matched versus 50.5% in mismatched patients ( P = .060), whereas extensive chronic GVHD was 45.6% versus 50%, respectively ( P = .310). Five-year OS was 62.2% for the matched patients and 27.9% for the mismatched patients ( P = .003) owing to a higher treatment-related mortality rate in mismatched patients ( P = .032). In multivariate analysis including age, gender, time until transplantation, disease phase, mismatched donor, ABO mismatch, number of CD34+ infused, acute and chronic GVHD, the significant unfavorable factors for OS were HLA mismatch and advanced disease phase. Conclusion A relatively low-dose ATG is effective in acute GVHD prophylaxis, leading to promising survival rates in matched transplants. Further comparative studies with adjusted ATG dose depending on Human leukocyte antigen disparity or alternative donors are warranted.

Pulse wave velocity (PWV), a measure of arterial stiffness, and intima‐media thickening (IMT), a measure of early atherosclerosis, are intermediate markers of cardiovascular disease which are predictive of cardiovascular events. Traditionally, both were thought to result from accumulative exposure to traditional cardiovascular risk factors. However, their association with risk factors in young adults in low‐income settings is unknown. We sought to investigate the association between PWV and IMT with traditional cardiovascular risk factors in the Andhra Pradesh Children and Parents Study cohort from Southern India. Male and female adults (N = 1440) aged between 20 and 24 years underwent measures of PWV and IMT. Exposure variables included smoking, body mass index (BMI), mean arterial pressure (MAP), glucose, homeostatic model assessment of insulin resistance (HOMA‐IR), total cholesterol, high‐density lipoprotein cholesterol (HDL‐cholesterol), and triglycerides. Association between outcome and exposure variables was assessed using linear regression analysis. Average values for PWV and IMT were 5.9 ± 0.6 m/s and 0.5 ± 0.1 mm. In univariable analysis, PWV associated with MAP, BMI, smoking, total cholesterol, glucose, and HOMA‐IR and IMT associated with MAP, BMI, tobacco use, and HDL‐cholesterol. In multivariable analysis, PWV remained strongly positively associated with MAP increasing by 0.5 m/s (P

Goal: We introduce a novel approach to estimate cardiac output (CO) and central systolic blood pressure (cSBP) from noninvasive measurements of peripheral cuff-pressure and carotid-to-femoral pulse wave velocity (cf-PWV). Methods: The adjustment of a previously validated one-dimensional arterial tree model is achieved via an optimization process. In the optimization loop, compliance and resistance of the generic arterial tree model as well as aortic flow are adjusted so that simulated brachial systolic and diastolic pressures and cf-PWV converge towards the measured brachial systolic and diastolic pressures and cf-PWV. The process is repeated until full convergence in terms of both brachial pressures and cf-PWV is reached. To assess the accuracy of the proposed framework, we implemented the algorithm on in vivo anonymized data from 20 subjects and compared the method-derived estimates of CO and cSBP to patient-specific measurements obtained with Mobil-O-Graph apparatus (central pressure) and two-dimensional transthoracic echocardiography (aortic blood flow). Results: Both CO and cSBP estimates were found to be in good agreement with the reference values achieving an RMSE of 0.36 L/min and 2.46 mmHg, respectively. Low biases were reported, namely −0.04 ± 0.36 L/min for CO predictions and −0.27 ± 2.51 mmHg for cSBP predictions . Significance: Our one-dimensional model can be successfully “tuned” to partially patient-specific standards by using noninvasive, easily obtained peripheral measurement data. The in vivo evaluation demonstrated that this method can potentially be used to obtain central aortic hemodynamic parameters in a noninvasive and accurate way.

Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. Methods: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. Results: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. Conclusion: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes.

Introduction Arterial stiffening may contribute to the increase of left ventricular mass (LVM) and the development of left ventricular hypertrophy (LVH). Although male gender has been also found to be an independent determinant of LVH, it is unknown if the adverse effect of increased aortic stiffening on LVM differs between males and females. Aim To evaluate the association of aortic stiffness as assessed by carotid-to-femoral pulse wave velocity (cf-PWV) with LVM and LVH in a general population and compare these associations between males and females. Methods Demographic, laboratory and clinical data of 1686 subjects (693 males and 993 females) from the cross-sectional, observational study “Corinthia” were analyzed. All subjects underwent applanation tonometry and pulse wave analysis for the measurement of cf-PWV and echocardiography examination for the computation of LVM which was adjusted by body surface area providing the LVM index (LVMI). Multivariate linear regression analysis was performed for the determination of independent factors related with LVMI. Receiver operator curve analysis (ROC) was used to compare the ability of cf-PWV to predict LVH, in males and females separately. Results In the female population, significant and independent determinants of LVMI were: age (beta=0.243, p Conclusion Increased aortic stiffness measured by cf-PWV is significantly related with increased LVMI regardless from age and other risk factors only in females. Moreover cf-PWV was a stronger predictor of left-ventricular hypertrophy in females than males. These findings should be further explored in prospective studies.

Introduction Exhaust fumes from diesel engines are a complex mixture of toxic compounds with a wide variety of harmful effects. The acute effects of diesel exhaust fumes on the cardiovascular system are well-known. However, their short-term impact has not been thoroughly studied. Purpose To study the acute and short-term (24 h) effects of diesel exhaust particles (DEPs) on endothelial function, arterial wall properties, inflammatory process and fibrosis-fibrinolysis status. Methods In this blind cross over study, 40 healthy volunteers (median age 40 years old) have been exposed to diesel exhaust particles (DEPs) and then to filtered air (FA) over a 2-hour session with a wash out period of 4 weeks. Exposure to DEPs was calibrated based on the mass of microparticles less than 2,5 microns in diameter (PM 2,5). Flow-mediated-dilation (FMD) was used to estimate endothelial function. Pulse wave velocity (PWV) and augmentation index (AIx) assessed central aortic stiffness and arterial reflected waves respectively. C reactive protein (CRP) was measured to determine the inflammatory status, as well as fibrinogen and protein C levels to evaluate the impact on the coagulation cascade. All measurements were performed before each session (T0), at the end of the 2 hours exposure session (T2) and 24 hours after completion of each session (T24). Variables with normal distribution are presented as mean±SD otherwise as median±SEM. Results At T0 of DEP and FA exposure there was no significant difference in FMD, PWV, AIX, CRP, protein C and fibrinogen levels. Exposure to DEP decreased significantly FMD (T0: 11.97±4.61% vs T2: 7.71±3.36% vs. T24: 6.17±3.19%, p Graph of results Conclusion Exposure to diesel exhaust fumes may have significant adverse effects on the cardiovascular system with impairment of endothelial function, arterial wall properties, inflammatory status and fibrosis-fibrinolysis parameters not only during the exposure period but as far as 24 hours after exposure. Acknowledgement/Funding None

Mathematical models of the arterial tree constitute a valuable tool to investigate the hemodynamics of aging and pathology. Rendering such models as patient specific could allow for the assessment of central hemodynamic variables of clinical interest. However, this task is challenging, particularly with respect to the tuning of the local area compliance that varies significantly along the arterial tree. Accordingly, in this study, we demonstrate the importance of taking into account the differential effects of aging on the stiffness of central and peripheral arteries when simulating a person’s hemodynamic profile. More specifically, we propose a simple method for effectively adapting the properties of a generic one-dimensional model of the arterial tree based on the subject’s age and noninvasive measurements of aortic flow and brachial pressure. A key element for the success of the method is the implementation of different mechanisms of arterial stiffening for young and old individuals. The designed methodology was tested and validated against in vivo data from a population of n = 20 adults. Carotid-to-femoral pulse wave velocity was accurately predicted by the model (mean error = 0.14 m/s, SD = 0.77 m/s), with the greatest deviations being observed for older subjects. In regard to aortic pressure, model-derived systolic blood pressure and augmentation index were both in good agreement (mean difference of 2.3 mmHg and 4.25%, respectively) with the predictions of a widely used commercial device (Mobil-O-Graph). These preliminary results encourage us to further validate the method in larger samples and consider its potential as a noninvasive tool for hemodynamic monitoring. NEW & NOTEWORTHY We propose a technique for adapting the parameters of a validated one-dimensional model of the arterial tree using noninvasive measurements of aortic flow and brachial pressure. Emphasis is given on the adjustment of the arterial tree distensibility, which incorporates the nonuniform effects of aging on central and peripheral vessel elasticity. Our method could find application in the derivation of important hemodynamic indices, paving the way for novel diagnostic tools.

Beside the well-known complications of poorly controlled, long-standing hypertension, milder abnormalities induced by early-stage hypertension have also been described. In our study, the authors examined the reversibility of changes induced by early-stage hypertension. The authors performed laboratory testing, ambulatory blood pressure monitoring, carotid intima-media thickness (IMT) measurement, evaluation of stiffness parameters, assessment of various cardiac and cerebral hemodynamic parameters during head-up tilt table (HUTT) testing, and neuropsychological examinations in 49 recently diagnosed hypertensive patients. Following baseline assessment, antihypertensive therapy was commenced. After one year of therapy, lower IMT values were found. Pulse wave velocity showed a borderline significant decrease. During HUTT, several hemodynamic parameters improved. The patients performed better on neuropsychological testing and reached significantly lower scores on questionnaires evaluating anxiety. The present study shows that early vascular changes and altered cognitive function observed in newly diagnosed hypertensive patients may improve with promptly initiated antihypertensive management.

Objective Increased resting heart rate as well as increased arterial stiffness are both independent predictors of cardiovascular events and mortality. Results of previous studies have failed to converge concerning the association between heart rate and arterial stiffness, regardless of other potential confounders, such as age, gender and particularly blood pressure (BP). We aimed to investigate: (a) the degree of association (if any) between resting heart rate and carotid-to-femoral pulse wave velocity (PWV), the gold standard index of arterial stiffness, (b) if the relationship between heart rate and PWV is mediated by BP levels and (c) whether their association is affected by the levels of aortic stiffening. Approach Demographic, hemodynamic, laboratory and clinical data of 1566 subjects from the cross-sectional observational 'Corinthia' study were analyzed using univariate and multivariate regression models. Mediation analysis was performed to test whether mean arterial pressure (MAP) is a significant mediator in the heart rate-PWV relationship. The total population was divided in two groups of low and high arterial stiffness according to the median PWV value (8.6 m s-1). Main results We found that (i) there is a significant association between heart rate and PWV, regardless of other confounding factors. An increase in heart rate by 20 b.p.m. can increase PWV by 0.5 m s-1. However, this association was significant only for subjects with increased aortic stiffness (PWV > 8.6 m s-1) and not for those with PWV ⩽ 8.6 m s-1. Further, (ii) heart rate-PWV association was partially mediated by MAP. Significance Increased resting heart rate is related to increased aortic stiffness, only in subjects with stiffer aortas, regardless of BP and other risk factors and subjects' characteristics. The synergistic prognostic effect of increased arterial stiffness and elevated heart rate on target organ damage, cardiovascular events and mortality should be explored in future studies.

Objective Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR), and ACS after prolonged follow-up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow-up. Design Prospective study in a tertiary hospital. Patients and Measurements Seventy-one patients with AI, (51 non-functioning [NFAI], 20 ACS), and 5.54±1.7 year follow-up underwent testing for autonomous cortisol secretion, Oral Glucose Tolerance Test to determine IR indices and adrenal imaging. Results At follow-up, 16/51 (31%) NFAI patients converted to ACS, while 2 with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary free cortisol (H-UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9.8% NFAI and 15% ACS, respectively) and 14 IR (17.6% NFAI and 25% ACS, respectively). Adenoma size increased from 2.1±0.8 to 2.3±0.8cm, whereas IR correlated with post-dexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν-UFC), to H-UFC, to C-ACS and ACS patients. Conclusions New-onset ACS developed in 31% patients with NFAI whereas 21% of NFAI patients had H-UFC levels. All AI patients as a group and the subgroups of N-UFC, H-UFC, C-ACS and ACS patients developed deterioration of metabolic parameters during follow-up that was more prominent in ACS patients. This article is protected by copyright. All rights reserved.

Balloon aortic valvuloplasty (BAV) has been used prior to valve implantation of a self-expandable valve as part of the transcatheter aortic valve implantation (TAVI) procedure. We aimed to evaluate the impact of BAV prior to TAVI.We retrospectively studied 203 consecutive patients who were treated either with (pre-BAV-TAVI group) or without BAV (D-TAVI group). Implantation depth (ID) was angiographically measured at non-coronary cusp (NCC) and left coronary cusp (LCC) at: the starting point (stage-1), before (stage-2), and after (stage-3) final bioprosthesis release. Paravalvular regurgitation (PVR) and 1-year clinical follow-up were recorded.Overall, from stage-1 to stage-3, prosthesis migrated toward the left ventricle, in both cusps and groups. At NCC a forward migration was observed from stage-1 to stage-2 in both groups (p0.001). In the pre-BAV-TAVI group only, at NCC, an upward migration decreased the ID from stage-2 to stage-3 (p=0.022). PVR ≥grade 2, immediately after expansion was more frequently observed in pre-BAV-TAVI group (41% vs 22%, respectively; p=0.024). However, PVR was similar at discharge. Clinical parameters were comparable between the two groups.The use of BAV prior to TAVI may have an impact on device final position, but not on short- and long-term clinical outcome.

'Cover index' has been proposed to appraise the congruence between the aortic annulus and the device, with the assumption of not taking into account the actual device implantation depth. The aim of this study was to investigate whether the annulus-prosthesis mismatch, as expressed with the new proposed 'true cover index' according to actual implantation depth, can predict aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI).Patients who had undergone TAVI with the self-expandable CoreValve device, were retrospectively studied. All available prosthesis sizes were ex-vivo scanned and the precise diameter at 0.3mm intervals along each device was measured. The 'true cover index' was evaluated, as a ratio of the following: 100×([prosthesis actual diameter at implantation depth-annulus diameter]/prosthesis actual diameter at implantation depth). AR was echocardiographically evaluated at discharge and 30days and classified as prominent if moderate, or trivial if none or mild.Overall, 120 patients who had undergone TAVI, were considered eligible for the study. 'True cover index' was statistically significantly lower among patients with prominent AR in comparison with trivial AR at discharge (5.7±4.8mm vs 9±5.1, p=0.025), as well as at one month post-TAVI (5.4±5.1mm vs 9.0±5.1, p=0.023), indicating increased AR for smaller index. After adjustment for severe annulus calcification, impaired baseline LVEF and previous valvuloplasty, it remained an independent predictor of one month prominent AR (OR: 0.854, CI: 0.730-0.999; p=0.048). 'True cover index' of4.3 was shown to predict one-month prominent AR with sensitivity =75% and specificity =82.5%.'True cover index' is strongly and independently correlated with the short and mid-term AR after CoreValve implantation.

Background: Transcatheter aortic valve implantation (TAVI) has undeniably earned a prestigious post in the quiver of interventional cardiologists against symptomatic severe aortic stenosis. Cerebrovascular events are listed within the most frequent complications. Methods: We performed a systematic search of EMBASE, MEDLINE, and the Cochrane library from inception to March 2016 for the following search terms (transcatheter AND antiplatelet) OR (transcatheter AND antithrombotic) to retrieve studies of dual antiplatelet treatment (DAPT) and single antiplatelet treatment (SAPT) in patients after TAVI to study thrombotic, hemorrhagic and cardiovascular events at 30 days post procedure. From a total of 208 records 4 studies met inclusion criteria. Results: In the included studies, 286 patients were enrolled in the DAPT group and 354 patients in the SAPT group. There was no difference in all-cause mortality, cardiovascular mortality, stroke, and myocardial infraction 30 days post TAVI between DAPT and SAPT. However, patients in the DAPT group had a significantly increased incidence of lethal and major bleeding at 30 days of follow-up and the incidence of the combined end-point of stroke, spontaneous MI, all-cause mortality and major bleeding was significantly higher in the DAPT group in comparison to the SAPT group. Conclusion: DAPT compared to SAPT in patients after TAVI increases incidence of hemorrhagic events with no benefits in terms of thrombotic events and cardiovascular mortality. However, these data must be interpreted cautiously and the choice of DAPT over SAPT must be based on an individual patient characteristic according to medical practice criteria.

Objective: Aortic (a) systolic blood pressure (SBP) is associated with arterial damage more consistently than brachial (b) SBP. However, it is unknown whether: (i) aSBP is normal in the presence of elevated bSBP, and vice versa; (ii) SBP classification on the basis of proposed bSBP and aSBP cut-off values, improves cardiovascular (CV) risk assessment. We tested (i) the frequency of 4 office SBP phenotypes: type I (both normal bSBP and aSBP); type II (high bSBP but normal aSBP); type III (normal bSBP but high aSBP), and type IV (both high bSBP and aSBP), (ii) the probability of each phenotype (using type I as reference) to be associated with increased arterial damage. Design and method: In a cohort study of 1861 participants (age: years 54 years, 49.1% males), we measured simultaneously bSBP, aSBP and carotid cross-sectional wall area (CSWA) with ultrasound. Results: Depending on the applied aSBP cut-off values, type II and type III phenotypes represented together 5–11 % of the studied population (0.9–3.4% and 1.8–10.3%, respectively). Subgroups with phenotypes II and III had significantly higher probability (by 2.3–3.3 and 3.3–8.9 times, respectively) as assessed by logistic regression analysis to present elevated carotid artery CSWA compared to the reference group, even after adjustment for diastolic blood pressure and other confounders. Conclusions: Defined on the basis of both bSBP and aSBP measurements, type II (i.e. isolated high bSBP) and type III (isolated high aSBP) are commonly observed and refine the detection of subgroups regarding the presence of arterial damage.

To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 × [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement.

Background Arterial stiffness measured under static conditions reclassifies significantly cardiovascular (CV) risk and associates with narrower retinal arterioles. However, arterial stiffness exhibits circadian variation, thus single static stiffness recordings do not correspond to the "usual" 24 hr, awake, and asleep average arterial stiffness. We aimed to test the hypothesis that ambulatory 24 hr, awake, and asleep aortic (a) pulse wave velocity (PWV) associate with retinal vessel calibers, independently of confounders and of static arterial stiffness, in hypertensive individuals free from diabetes and CV disease. Methods Digital retinal images were obtained (181 individuals, age: 53.9±10.7 years, 55.2% men) and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively); ambulatory (24 hr, awake, asleep) and static office aPWV were estimated by Mobil-O-Graph; and static office carotid to femoral (cf) PWV by SphygmoCor. Results Regression analysis performed in 320 gradable retinal images showed that, after adjustment for confounders: (i) ambulatory aPWV was significantly associated with narrower retinal arterioles but not with venules; (ii) asleep aPWV had stronger associations with CRAE than awake aPWV; (iii) both ambulatory aPWV and cfPWV were associated mutually independently with narrower retinal arterioles; aPWV introduction in the model of cfPWV, improved model's R2 (P = 0.012). Similar discriminatory ability of 24 hr aPWV and of cfPWV to detect the presence of retinal arteriolar narrowing was found. Conclusion Ambulatory aPWV, estimated by an operator-independent method, provides additional information to cfPWV regarding the associations of arterial stiffness with the retinal vessel calibers.

See related article, pp 148–157 The role of office and ambulatory 24-hour measurement of brachial blood pressure (BP) on the assessment and prediction of cardiovascular risk and mortality has been well established. In addition, the independent predictive value of office measurement of carotid-to-femoral pulse wave velocity (PWV), a surrogate of arterial stiffness, has been reported in longitudinal prospective studies and further confirmed by several meta-analyses. Indeed, the assessment of arterial stiffness at the office or clinical setting has gained a place in the latest (2013) European guidelines with an indication (Class IIa; Level of Evidence B) for evaluation of subclinical organ damage in hypertensive patients. Along with the growing clinical interest on the field, a variety of promising devices were introduced by the industry, which, however, led to known and new methodological concerns and debates thus resulting to the establishment of consensus reports and guidelines for their standardization.1 Several parallel studies have investigated the potential predictive value of central BP and aortic wave reflections, beyond and above peripheral (ie, brachial) BP values, but the provided evidence remains cloudy. With the advancement of technology, similarly to the ambulatory BP monitoring (ABPM) at the brachial artery, it is now feasible to monitor and evaluate the 24-hour (or longer) variation of arterial stiffness, wave reflections, and central BP at ambulatory conditions.2 Several commercially available devices exist for the above purposes as thoroughly described previously,3 providing a new tool to assess vascular function and properties at a circadian level. Numerous studies have demonstrated the prognostic value of ambulatory arterial stiffness in various populations and especially in hypertensive patients.3 Most commonly, the ambulatory arterial stiffness index, calculated using BP indices derived by brachial ABPM, has been applied for the assessment of 24-hour variation of arterial stiffness. Recently, the RENIS cohort investigated …

Reference EPFL-ARTICLE-227670doi:10.1097/Hjh.0000000000001247Afficher la publication dans Web of Science Notice creee le 2017-05-01, modifiee le 2017-05-07

Abstract. Background: The 2017 ACC/AHA blood pressure (BP) guidelines generated controversies due to the new proposed BP cut-off values defining hypertension. We aimed to assess aortic stiffness of subjects who are reclassified as stage 1 hypertensive according to the new guidelines and compare them with the subjects of “elevated BP” category. Patients and methods. Data from the “Corinthia” study, an observational, cross-sectional survey of 2,043 participants were analyzed. Subjects were classified into 4 groups: group A: systolic pressure (SBP) 120–129 and diastolic pressure (DBP) < 80 mmHg, group B: SBP 130–139 or DBP 80–89 mmHg, group B1: SBP 130–139 and DBP < 80 mmHg and group B2: SBP 130–139 and DBP 80–89 mmHg. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity (PWV). A value of PWV > 10m/s was consider indicative of asymptomatic organ damage while values of PWV exceeded the 90 % percentile for each age group were consider as abnormal. Results: Groups B, B1 and B2 have significantly increased PWV compared to group A, independently from age and other risk factors (PWV: 9.2 ± 2.8 vs 9.4 ± 2.7 vs 8.6 ± 2.5 vs 8.1 ± 2.3 m/s, p < 0.01, respectively). The prevalence of PWV > 10 m/s and abnormal PWV values in group A was significantly lower than the corresponding prevalence in randomly selected, age-matched subjects from group B (13.5 % vs 24.4 %, p = 0.027 and 5.6 % vs 14.2 %, p = 0.022, respectively). Conclusions: The reclassified subjects as stage 1 hypertensive by the new guidelines have a significantly increased aortic stiffness and greater prevalence in asymptomatic aortic damage compared to subjects with elevated BP. This finding may indirectly explain the increased cardiovascular risk of this group.

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.

Artificial pancreas is a technology that minimizes user input by bridging continuous glucose monitoring and insulin pump treatment, and has proven safety in the adult population. The purpose of this systematic review and meta-analysis is to evaluate the efficacy of closed-loop (CL) systems in the glycemic control of non-adult type 1 diabetes patients in both a pairwise and network meta-analysis (NMA) context and investigate various parameters potentially affecting the outcome.Literature was systematically searched using the MEDLINE (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2018), Clinicaltrials.gov (2008-2018) and Google Scholar (2004-2018) databases. Studies comparing the glycemic control in CL (either single- or dual-hormone) with continuous subcutaneous insulin infusion (CSII) in people with diabetes (PWD) aged18 years old were deemed eligible. The primary outcome analysis was conducted with regard to time spent in the target glycemic range. All outcomes were evaluated in NMA in order to investigate potential between-algorithm differences. Pairwise meta-analysis and meta-regression were performed using the RevMan 5.3 and Open Meta-Analyst software. For NMA, the package pcnetmetain R 3.5.1 was used.The meta-analysis was based on 25 studies with a total of 504 PWD. The CL group was associated with significantly higher percentage of time spent in the target glycemic range (Mean (SD): 67.59% (SD: 8.07%) in the target range and OL PWD spending 55.77% (SD: 11.73%), MD: -11.97%, 95% CI [-18.40, -5.54%]) and with lower percentages of time in hyperglycemia (MD: 3.01%, 95% CI [1.68, 4.34%]) and hypoglycemia (MD: 0.67%, 95% CI [0.21, 1.13%]. Mean glucose was also decreased in the CL group (MD: 0.75 mmol/L, 95% CI [0.18-1.33]). The NMA arm of the study showed that the bihormonal modality was superior to other algorithms and standard treatment in lowering mean glucose and increasing time spent in the target range. The DiAs platform was superior to PID in controlling hypoglycemia and mean glucose. Time in target range and mean glucose were unaffected by the confounding factors tested.The findings of this meta-analysis suggest that artificial pancreas systems are superior to the standard sensor-augmented pump treatment of type 1 diabetes mellitus in non-adult PWD. Between-algorithm differences are also addressed, implying a superiority of the bihormonal treatment modality. Future large-scale studies are needed in the field to verify these outcomes and to determine the optimal algorithm to be used in the clinical setting.

Background Neuroinflammation, impaired brain insulin signaling, and neuronal apoptosis may be interrelated in the pathophysiology of people with Alzheimer disease (AD) and diabetes, either type 1 or 2 diabetes (T1D or T2D, respectively). Methods We studied 116 patients: 41 with AD, 20 with T1D, 21 with T2D, and 34 healthy controls. The number (n) of cytokine-secreting peripheral blood mononuclear cells (PBMCs) before and after mitogenic stimulation was determined for interleukin 1β (IL1β), interleukin 6 (IL6), tumor necrosis factor (TNF) by the enzyme-linked-immuno-spot assay. Serum concentrations of C-reactive protein (CRP) and Fas ligand (FASLG) were determined by ELISA. Results The studied subgroups did not differ in sex but differed in age. Higher CRP concentrations were detected in the AD group than in the T1D group (P = 0.02) and lower in controls (P < 0.001). The nPBMCs was higher in AD patients after stimulation than in basal conditions: after stimulation in nTNF (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.001 vs control), nIL6 (P = 0.039 vs T2D; P < 0.001 vs T1D; P = 0.007 vs control), and nIL1β (P = 0.03 vs control). The nPBMCs increased after stimulation with ΡΜA in all the subgroups (P < 0.001). FASLG in the AD group displayed statistically higher concentrations than in all other subgroups (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.012 vs control). The nPBMCs was positively correlated with plasma concentrations of FASLG in the AD subgroup. Conclusions Patients with AD display a low-grade systemic inflammation compared to people with diabetes. The FAS–FASLG pathway has a potential role because FASLG concentrations are positively correlated with the inflammatory response in AD. However, this positive correlation cannot be seen in people with diabetes, at least not with the apoptotic markers used in the present study.