[CME/Answers: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice]. / CME/Réponses: L'hypertension artérielle et la pandémie COVID-19: Ce qu'il faut retenir en pratique médicale.

CME/Answers: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice Abstract. The COVID-19 pandemic represents a major public health problem. A fraction of the population is at increased risk of developing complications of this disease, in particular older subjects as well as diabetic, obese and hypertensive patients. With regard to patients with high blood pressure, the existence of an increased risk remains to be confirmed in large controlled trials. So far the findings regarding this question are reassuring, whether these patients are treated or not. There seems to be no reason to worry when using blockers of the renin-angiotensin system. The observations available to date suggest that COVID-19 vaccine can be administered safely to hypertensive patients. In conclusion, there is no reason to implement changes in the care of hypertensive patients due to the pandemic.

[CME/Answers: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice]. / CME/Antworten: Hypertonie und die COVID-19-Pandemie: Was in der medizinischen Praxis zu beachten ist.

CME/Answers: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice Abstract. The COVID-19 pandemic represents a major public health problem. A fraction of the population is at increased risk of developing complications of this disease, in particular older subjects as well as diabetic, obese and hypertensive patients. With regard to patients with high blood pressure, the existence of an increased risk remains to be confirmed in large controlled trials. So far the findings regarding this question are reassuring, whether these patients are treated or not. There seems to be no reason to worry when using blockers of the renin-angiotensin system. The observations available to date suggest that COVID-19 vaccine can be administered safely to hypertensive patients. In conclusion, there is no reason to implement changes in the care of hypertensive patients due to the pandemic.

[CME: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice]. / CME: Hypertonie und die COVID-19-Pandemie: Was in der medizinischen Praxis zu beachten ist.

CME: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice Abstract. The COVID-19 pandemic represents a major public health problem. A fraction of the population is at increased risk of developing complications of this disease, in particular older subjects as well as diabetic, obese and hypertensive patients. With regard to patients with high blood pressure, the existence of an increased risk remains to be confirmed in large controlled trials. So far the findings regarding this question are reassuring, whether these patients are treated or not. There seems to be no reason to worry when using blockers of the renin-angiotensin system. The observations available to date suggest that COVID-19 vaccine can be administered safely to hypertensive patients. In conclusion, there is no reason to implement changes in the care of hypertensive patients due to the pandemic.

[CME: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice]. / CME: L'hypertension artérielle et la pandémie COVID-19: Ce qu'il faut retenir en pratique médicale.

CME: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice Abstract. The COVID-19 pandemic represents a major public health problem. A fraction of the population is at increased risk of developing complications of this disease, in particular older subjects as well as diabetic, obese and hypertensive patients. With regard to patients with high blood pressure, the existence of an increased risk remains to be confirmed in large controlled trials. So far the findings regarding this question are reassuring, whether these patients are treated or not. There seems to be no reason to worry when using blockers of the renin-angiotensin system. The observations available to date suggest that COVID-19 vaccine can be administered safely to hypertensive patients. In conclusion, there is no reason to implement changes in the care of hypertensive patients due to the pandemic.

Résumé. La pandémie COVID-19 représente un problème de santé publique majeur. Une partie de la population est à risque accru de développer des complications de cette maladie, en particulier les personnes âgées ainsi que les malades diabétiques, les obèses et, possiblement, les malades hypertendus. Pour ces derniers, cela reste à être confirmé dans des études contrôlées de grande envergure. Les connaissances accumulées à ce jour sont rassurantes, que les malades soient traités ou non. Il n'y a pas de crainte à avoir en ce qui concerne la prise de médicaments antihypertenseurs, y compris les bloqueurs du système rénine-angiotensine. Les premières observations indiquent que le vaccin anti-COVID-19 peut être administré chez le malade hypertendu avec la meme efficacité que le normotendu. En conclusion il n'y a pas de raison de prendre en charge le malade hypertendu autrement qu'avant l'apparition de la pandémie.

Axon reflex-mediated vasodilation is reduced in proportion to disease severity in TTR-FAP.

OBJECTIVE: To evaluate the area of the vascular flare in familial amyloid polyneuropathy (FAP). METHODS: Healthy controls and patients with genetically confirmed FAP were prospectively examined, on the upper and lower limbs, for thermal sensitivity (Medoc TSA-II thermal analyzer) and for axon reflex-mediated flare. The latter was induced by iontophoresis of histamine on the forearm and leg on 2 different visits. We used laser Doppler imaging (LDI) to measure the flare area (LDIflare). RESULTS: Six patients had FAP of variable severity; 1 had generalized analgesia secondary to leprosy (used as a positive control). The median Neurological Impairment Score-Lower Limbs (NIS-LLs) was 6 (0-27). The warmth detection thresholds in the feet were higher in patients (median 43°, interquartile range 39.0°-47.6°) compared with controls (37.4°, 35.3°-39.2°), indicating small fiber impairment. On the leg, LDIflare was smaller in the patients on 2 consecutive visits (controls: median 13.0 and 13.3 cm2, IQR 9.7-22.8 and 8.3-16.9; patients 6.9 and 8.0 cm2, 2.6-10.8 and 6.4-12.1; p = 0.011). LDIflare on the leg was correlated with NIS-LL (Spearman rank correlation 0.73, p = 0.09 on the first visit; Spearman rank correlation 0.85, p = 0.03 on the second visit). CONCLUSIONS: Our study underscores that histamine-induced axon reflex-mediated vascular flare on the leg is reduced in proportion to disease severity in patients with FAP.

Use of oscillometric devices in atrial fibrillation: a comparison of three devices and invasive blood pressure measurement.

BACKGROUND: The use of automated (oscillometric) blood pressure (BP) devices is not validated in atrial fibrillation (AF) patients. OBJECTIVES: To assess the reliability of three oscillometric BP devices, and the agreement with invasive arterial blood pressure(IBP) in AF patients. METHODS: 48 AF patients with randomized sequences of 10 consecutive BP measurements with two pairs of devices: (1) OmronR7™(wrist) and OmronHEM907™(arm); (2) OmronR7™ and Microlife WatchBPhome(arm). Reliability and agreement of each device were assessed by the intra-class correlation coefficient (ICC) for the continuous BP measurements and Bland & Altman methodology, respectively. In 10 additional AF patients, 10 consecutive measurements with IBP and OmronHEM907™, and IBP and Microlife WatchBPhome were performed. RESULTS: The OmronR7™ was not able to obtain any BP Readings. Arm devices presented better ICC for systolicBP(SBP) than for diastolicBP(DBP) (Omron HEM907™:0.94 [0.90; 0.97] vs. 0.77 [0.67; 0.89]; Microlife WatchBPhome:0.92 [0.88; 0.96] vs.0.79 [0.69; 0.89]).The correlation coefficient between Microlife WatchBPhome and IBP computed using the average of repeated measurements from two to ten measurements improved up to the third and remained stable afterwards. The agreement between IBP and SBP, and IBP and DBP, was moderate as illustrated by a wide limit of agreement [-24; 26](SBP) and [-15;17](DBP) for Microlife WatchBPHome, respectively and [-30; 13](SBP) and [-7; 15](DBP) for OmronHEM907. CONCLUSIONS: BP measurement using the two arm oscillometric devices achieved a high reliability for SBP. The agreement between IBP and arm devices was low but using the average of three consecutive measurements improved the results substantially.

Natriuretic Peptide Receptor B modulates the proliferation of the cardiac cells expressing the Stem Cell Antigen-1.

Brain Natriuretic Peptide (BNP) injections in adult "healthy" or infarcted mice led to increased number of non-myocyte cells (NMCs) expressing the nuclear transcription factor Nkx2.5. The aim of this study was to identify the nature of the cells able to respond to BNP as well as the signaling pathway involved. BNP treatment of neonatal mouse NMCs stimulated Sca-1+ cell proliferation. The Sca-1+ cells were characterized as being a mixed cell population involving fibroblasts and multipotent precursor cells. Thus, BNP treatment led also to increased number of Sca-1+ cells expressing Nkx2.5, in Sca-1+ cell cultures in vitro and in vivo, in the hearts of neonatal and adult infarcted mice. Whereas BNP induced Sca-1+ cell proliferation via NPR-B receptor and protein kinase G activation, CNP stimulated Sca-1+ cell proliferation via NPR-B and a PKG-independent mechanism. We highlighted here a new role for the natriuretic peptide receptor B which was identified as a target able to modulate the proliferation of the Sca-1+ cells. The involvement of NPR-B signaling in heart regeneration has, however, to be further investigated.

Global cardiovascular protection in chronic kidney disease.

The development and progression of cardiovascular disease (CVD) and renal disorders are very closely related. In patients with chronic kidney disease (CKD), therapies proven to protect the cardiovascular and renal systems simultaneously are generally used only at low doses or not at all. In particular, patients with CKD who receive angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid-receptor antagonists (MRAs) often do not experience complete blockade of the renin-angiotensin-aldosterone system, primarily owing to the risk of hyperkalaemia. In this Review, we provide an overview of the available treatments required for adequate cardiorenal protection in patients with CKD. Drugs such as ß-blockers that interfere with renin secretion will be discussed, in addition to agents that can prevent hyperkalaemia, such as potassium binders and nonsteroidal MRAs. Furthermore, the current literature on the role of statins, in addition to new compounds and dosing recommendations for the treatment of patients with CKD will also be reviewed. Further studies with these new compounds and doses are needed to ascertain whether these approaches can improve the long-term cardiovascular and renal prognosis in patients with CKD.

Thoracic fat volume is independently associated with coronary vasomotion.

PURPOSE: Thoracic fat has been associated with an increased risk of coronary artery disease (CAD). As endothelium-dependent vasoreactivity is a surrogate of cardiovascular events and is impaired early in atherosclerosis, we aimed at assessing the possible relationship between thoracic fat volume (TFV) and endothelium-dependent coronary vasomotion. METHODS: Fifty healthy volunteers without known CAD or major cardiovascular risk factors (CRFs) prospectively underwent a (82)Rb cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, and MBF response to cold pressor testing (CPT-MBF) and adenosine (i.e., stress-MBF). TFV was measured by a 2D volumetric CT method and common laboratory blood tests (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hsCRP) were performed. Relationships between CPT-MBF, TFV and other CRFs were assessed using non-parametric Spearman rank correlation testing and multivariate linear regression analysis. RESULTS: All of the 50 participants (58 ± 10y) had normal stress-MBF (2.7 ± 0.6 mL/min/g; 95 % CI: 2.6-2.9) and myocardial flow reserve (2.8 ± 0.8; 95 % CI: 2.6-3.0) excluding underlying CAD. Univariate analysis revealed a significant inverse relation between absolute CPT-MBF and sex (ρ = -0.47, p = 0.0006), triglyceride (ρ = -0.32, p = 0.024) and insulin levels (ρ = -0.43, p = 0.0024), HOMA-IR (ρ = -0.39, p = 0.007), BMI (ρ = -0.51, p = 0.0002) and TFV (ρ = -0.52, p = 0.0001). MBF response to adenosine was also correlated with TFV (ρ = -0.32, p = 0.026). On multivariate analysis, TFV emerged as the only significant predictor of MBF response to CPT (p = 0.014). CONCLUSIONS: TFV is significantly correlated with endothelium-dependent and -independent coronary vasomotion. High TF burden might negatively influence MBF response to CPT and to adenosine stress, even in persons without CAD, suggesting a link between thoracic fat and future cardiovascular events.

Ambulatory and home blood pressure monitoring in people with chronic kidney disease. Time to abandon clinic blood pressure measurements?

PURPOSE OF REVIEW: There is currently much interest in the usefulness of out-of-office blood pressure (BP) for the diagnosis and the management of hypertension in patients with chronic kidney disease (CKD). This is not to suggest that office BP should be disregarded and we will take the opportunity to stress how it could be improved. RECENT FINDINGS: Arterial hypertension constitutes a very relevant cardiovascular and renal risk factor in patients with CKD. To assess this risk, the best tool is ambulatory BP monitoring (ABPM), as it allows the detection of masked hypertension, masked untreated hypertension (MUCH) and nondipping pattern, conditions known to be associated with target organ damage that further contributes to increased risk to the patient. Home BP monitoring (HBPM) cannot fully substitute for ABPM because of the absence of BP data during the night. Despite this, there are good reasons to use HBPM systematically in patients with CKD during long-term follow-up. SUMMARY: In the individual patient office, BP may significantly differ from out-of-office measurements. This shortcoming can be attenuated by repeated measurement at every visit, but even if office BP is considered normal, it is still highly desirable to obtain out-of-office data.

Impact of body tilt on the central aortic pressure pulse.

The present work was undertaken to investigate, in young healthy volunteers, the relationships between the forward propagation times of arterial pressure waves and the timing of reflected waves observable on the aortic pulse, in the course of rapid changes in body position. 20 young healthy subjects, 10 men, and 10 women, were examined on a tilt table at two different tilt angles, -10° (Head-down) and + 45° (Head-up). In each position, carotid-femoral (Tcf) and carotid-tibial forward propagation times (Tct) were measured with the Complior device. In each position also, the central aortic pressure pulse was recorded with radial tonometry, using the SphygmoCor device and a generalized transfer function, so as to evaluate the timing of reflected waves reaching the aorta in systole (onset of systolic reflected wave, sT1r) and diastole (mean transit time of diastolic reflected wave, dMTT). The position shift from Head-up to Head-down caused a massive increase in both Tct (women from 130 ± 10 to 185 ± 18 msec P < 0.001, men from 136 ± 9 to 204 ± 18 msec P < 0.001) and dMTT (women from 364 ± 35 to 499 ± 33 msec P < 0.001, men from 406 ± 22 to 553 ± 21 msec P < 0.001). Mixed model regression showed that the changes in Tct and dMTT observed between Head-up and Head-down were tightly coupled (regression coefficient 2.1, 95% confidence interval 1.9-2.3, P < 0.001). These results strongly suggest that the diastolic waves observed on central aortic pulses reconstructed from radial tonometric correspond at least in part to reflections generated in the lower limbs.

Eligibility to treatment and economic effect of the implementation of the new U.S. or European Society of Hypertension/European Society of Cardiology hypertension guidelines.

OBJECTIVE: To evaluate the population and economic impact of implementing the new Joint National Committee (JNC) or European Society of Hypertension (ESH)/European Society of Cardiology (ESC) hypertension guidelines in the Swiss population. METHODS: Cross-sectional, population-based sample (6708 participants) collected between 2003 and 2006 in the city of Lausanne, Switzerland. Blood pressure categories were defined according to both the JNC (JNC-7 and JNC-8) and the ESH/ESC (2007 and 2013) guidelines. RESULTS: The proportion of participants aged 35-60 years eligible for drug treatment was 25.6% [95% confidence interval (CI) 24.4-26.9%] and 24.8% (95% CI 23.6-26.0%) for the JNC-7 and the JNC-8 guidelines, respectively; for participants aged 60-75 years, the values were 62.3% (95% CI 60.1-64.5%) and 46.8% (95% CI 44.5-49.0%), respectively. Shifting from the JNC-7 to the JNC-8 guidelines would lead to an annual saving of 163.6 million Swiss francs (187.7 million US dollars or 134.5 million European €). The proportion of participants aged 35-75 years without chronic kidney disease, diabetes mellitus or reported history of cardiovascular disease and eligible for treatment was 30.2% (95% CI 29.0-31.4%) for the ESH/ESC 2007 and 2013 guidelines. For participants with chronic kidney disease, diabetes mellitus or reported history of cardiovascular disease, the values were 73.6% (95% CI 70.8-76.3%) and 55.6% (95% CI 52.5-58.8%), respectively. Shifting from the ESH/ESC 2007 to the ESH/ESC 2013 guidelines would lead to an annual saving of 86.9 million Swiss francs (99.5 million US dollars or 71.4 million European €). CONCLUSION: In Switzerland, shifting from the JNC-7 to the JNC-8 guidelines or from the ESH/ESC 2007 to the ESH/ESC 2013 guidelines would decrease the prevalence of patients eligible for treatment and increase the percentage of treated patients within blood pressure goals. Both strategies lead to potential savings in antihypertensive drug treatment.

Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse.

Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response important for myocardial healing, but which may also contribute to adverse ventricular remodelling. Such inflammation is initiated by molecular danger signals released by damaged myocardium, which induce innate immune responses by activating toll-like receptors (TLRs). Detrimental roles have been recently reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore evaluated the role of TLR5, expressed at high level in the heart, in the development of myocardial damage and inflammation acutely triggered by MIR. TLR5(-/-) and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h reperfusion). We measured infarct size, markers of cardiac oxidative stress, myocardial phosphorylation state of mitogen-activated protein (MAP) kinases and AKT, expression levels of chemokines and cytokines in the heart and plasma, as well as cardiac function by echography and conductance volumetry. TLR5-deficient mice had normal cardiac morphology and function under physiological conditions. After MIR, the absence of TLR5 promoted an increase in infarct size and myocardial oxidative stress. Lack of TLR5 fostered p38 phosphorylation, reduced AKT phosphorylation and markedly increased the expression of inflammatory cytokines, whereas it precipitated acute LV (left ventricle) dysfunction. Therefore, contrary to the detrimental roles of TLR2, TLR3 and TLR4 in the infarcted heart, TLR5 is important to limit myocardial damage, inflammation and functional compromise after MIR.

Brain natriuretic peptide is able to stimulate cardiac progenitor cell proliferation and differentiation in murine hearts after birth.

Brain natriuretic peptide (BNP) contributes to heart formation during embryogenesis. After birth, despite a high number of studies aimed at understanding by which mechanism(s) BNP reduces myocardial ischemic injury in animal models, the actual role of this peptide in the heart remains elusive. In this study, we asked whether BNP treatment could modulate the proliferation of endogenous cardiac progenitor cells (CPCs) and/or their differentiation into cardiomyocytes. CPCs expressed the NPR-A and NPR-B receptors in neonatal and adult hearts, suggesting their ability to respond to BNP stimulation. BNP injection into neonatal and adult unmanipulated mice increased the number of newly formed cardiomyocytes (neonatal: +23 %, p = 0.009 and adult: +68 %, p = 0.0005) and the number of proliferating CPCs (neonatal: +142 %, p = 0.002 and adult: +134 %, p = 0.04). In vitro, BNP stimulated CPC proliferation via NPR-A and CPC differentiation into cardiomyocytes via NPR-B. Finally, as BNP might be used as a therapeutic agent, we injected BNP into mice undergoing myocardial infarction. In pathological conditions, BNP treatment was cardioprotective by increasing heart contractility and reducing cardiac remodelling. At the cellular level, BNP stimulates CPC proliferation in the non-infarcted area of the infarcted hearts. In the infarcted area, BNP modulates the fate of the endogenous CPCs but also of the infiltrating CD45(+) cells. These results support for the first time a key role for BNP in controlling the progenitor cell proliferation and differentiation after birth. The administration of BNP might, therefore, be a useful component of therapeutic approaches aimed at inducing heart regeneration.

Cutting edge: IL-1α is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.

Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88(-/-) fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1ß, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1α-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1α in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1α as a crucial early danger signal triggering post-MI inflammation.

[Hypertension and medication compliance: a challenge every day]. / Hypertension et adhérence thérapeutique: un challenge de tous les jours.

Hypertension is a cardiovascular risk factor frequently encountered in everyday practice. A drug therapy is often necessary to normalize blood pressure. However, despite adequate intensive drug treatment, adequate blood pressure target are not reached. Lack of adherence to treatment is often the cause. This article reviews various techniques for assessing patients' adherence and offers several ways to improve it.

L'hypertension artérielle est un facteur de risque cardiovasculaire fréquemment rencontré dans la pratique quotidienne. Une prise en charge médicamenteuse est très souvent nécessaire afin de normaliser la pression artérielle. Il arrive cependant que le traitement médicamenteux intensif ne permette pas d'atteindre les cibles tensionnelles. Un manque d'adhérence au traitement en est fréquemment la cause. Cet article passe en revue diverses techniques pour évaluer l'adhérence des patients et propose plusieurs moyens afin de l'améliorer.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

OBJECTIVE: This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging. METHODS: We assessed, in young (18-30 years, n = 13) and aged males (≥60 years, n = 13), the thigh, forearm, and forehead's skin vasodilatory response to local heating (LTH) with a LDI. In each subject and at each location, local Tskin was brought from 34°C (baseline) to 39 or 41°C for 30 minutes, to effect submaximal vasodilation, with maximal vasodilation then elicited by further heating to 44°C. RESULTS: The CVCs evaluated at baseline and after maximal vasodilation (CVCmax ) were higher in the forehead than in the two other anatomical locations. On all locations, CVCmax decreased with age but less markedly in the forehead compared to the two other locations. When expressed in % of CVCmax , the plateau increase of CVCs in response to submaximal temperatures (39 and 41°C) did not vary with age, and minimally so with location. CONCLUSION: Skin aging, whether intrinsic or combined with photoaging, reduces the maximal vasodilatory capacity of the dermal microcirculation, but not its reactivity to local heating.