The Critical Role of Community Pharmacists in Blood Pressure Monitoring.

Arterial hypertension is the most important modifiable risk factor for cardiovascular morbidity and mortality. In some countries, pharmacists' patient-centered approach has become a common practice, and their role in supporting the management of cardiovascular disease has been successfully developed for years. In particular, recent findings have confirmed benefits of pharmacist-provided hypertension care. Current guidelines emphasize the need for regular BP measurements in subjects age 40 years and older, who are at increased risk of hypertension. A panel of experts in cardiology, hypertensiology, family medicine, and pharmacy presented a narrative review of implementing community pharmacy blood pressure (CPBP) measurements into Polish pharmacy practice to assist pharmacists in CPBP readings. The paper focuses on basic aspects of management of untreated patients with elevated blood pressure levels, as well as management of individuals diagnosed with hypertension, who should follow their primary care physicians' recommendations for anti-hypertensive therapy. The article also includes a few important aspects related to CPBP measurement, such as equipment and techniques. Development of ready-made schemes of procedures for patients with different results of blood pressure measurement could ensure a uniform standard of services provided by pharmacists. This gives an opportunity to provide such patients with medical care and initiate treatment, and facilitates effective maintenance of BP in hypertensive subjects. This article reviews the role of pharmacists in Poland in screening for hypertension by taking blood pressure measurements.

May Measurement Month 2021: an analysis of blood pressure screening results from Poland.

May Measurement Month 2021 (MMM21) is the fourth edition of the global initiative in Poland initiated by the International Society of Hypertension (ISH) and aimed at raising awareness of hypertension and the need for blood pressure (BP) screening. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in 132 sites - between May and September 2021. Blood pressure was measured in 1699 subjects (mean age: 40.8 ± 17.0 years; 68.8% females). After multiple imputation, the age and sex standardized systolic and diastolic BP was 126.6/78.7 mmHg for the entire group, 133.8/81.9 mmHg in individuals on antihypertensive medication, and 125.4/78.6 mmHg in those not taking antihypertensive drugs. The proportion of subjects with high BP (≥140/90 mmHg) were: 30.9% for the entire group, 40.4% in subjects taking antihypertensive drugs, and 17.9% in those not taking antihypertensive drugs. Of all participants, 33.9% were in the age range of 18-29 years and we observed higher BP levels and more frequent BP elevation in males in this age group. These data provide unique insights into the hypertension rates during the COVID-19 pandemic. Due to the associated restrictions, only limited data could be obtained for older adults. Interestingly, among young Polish participants, the rate of hypertension and the level of BP were higher in males compared to females, suggestive perhaps of a higher susceptibility of males to experience a rise in BP during specific circumstances associated with a pandemic.

Impact of type 1 diabetes and its duration on wall-to-lumen ratio and blood flow in retinal arterioles.

BACKGROUND: Subclinical damage to both the small and large vessels may contribute to the development and progression of cardiovascular disease. Scanning laser Doppler flowmetry (SLDF), an established method used to measure retinal microcirculation, has been successfully applied in hypertensive and post-stroke patients. METHODS: Retinal microcirculation was assessed in 158 patients with type 1 diabetes and 38 age-matched healthy controls. The diabetics were divided into 3 groups: group A with diabetes duration <12 months, group B with diabetes with 1-10 years, and group C >10 years of diabetes. Retinal capillary structure and perfusion were evaluated using a Heidelberg retina flowmeter and automatically analyzed with full-field perfusion imaging. RESULTS: Age and BMI were comparable in all the diabetic patients and the controls (mean age 24.8 ± 4.7 years, mean BMI 22.9 ± 4.1). In the univariate analyses, RCF (retinal capillary flow) was significantly higher in group A (297 ± 121 arbitrary units [AU]) vs group B (236 ± 52 AU; p = 0.007) and group C (236 ± 70 AU; p = 0.008) and comparable to that of the controls (p = 0.46). Additionally, the WLR (Wall-to-Lumen Ratio) was highest in group C compared to the other diabetic subgroups and controls (p = 0.001). Multivariate regression analyses including age, BMI, sex, HbA1c, smoking, systolic blood pressure, and diabetes duration as covariates, showed, that only diabetes duration was significantly associated with WLR variations, whereas HbA1c was significantly linked to retinal capillary flow levels. CONCLUSIONS: New-onset diabetes is associated with an increase in RCF, which then gradually decreased with the duration of the disease. Structural changes of the retinal arterioles estimated via WLR are evident later in the course of diabetes, especially when the disease duration exceeded 10 years.

Aortic stiffness is not only associated with structural but also functional parameters of retinal microcirculation.

OBJECTIVE: The aim of the study was to test the hypothesis that alterations in large arteries are associated with microvascular remodelling and decreased retinal capillary blood flow. METHODS: The study group comprised of 88 patients with essential hypertension and 32 healthy controls. Retinal microcirculation was evaluated by scanning laser Doppler flowmetry. Macrovascular changes were assessed on the basis of arterial stiffness measurement (carotid-femoral pulse wave velocity), its hemodynamic consequences (central pulse pressure, augmentation pressure, augmentation index) and intima media thickness of common carotid artery. RESULTS: Pulse wave velocity was inversely correlated to mean retinal capillary blood flow in hypertensive patients (R = -0.32, p < 0.01). This relationship remained significant in multivariate regression analysis after adjustment for age, sex, central systolic blood pressure (BP) and body mass index (ß = -31.27, p < 0.001). Lumen diameter (LD) of retinal arterioles was significantly smaller in hypertensive then normotensive subjects (79.4 vs. 83.8, p = 0.03). Central and brachial systolic, diastolic and mean BPs were significantly correlated with LD and outer diameter of retinal arterioles. The relationship between LD and central BPs remained significant in multivariate analysis (ß = -0.15, p = 0.03 for cSBP; ß = -0.22, p = 0.04 for cDBP; ß = -0.21, p = 0.03 for cMBP). Moreover, in a subgroup with cardiac damage central and brachial pulse pressure were positively associated with retinal wall thickness, wall cross sectional area, and wall to lumen ratio. CONCLUSION: In conclusion, the study provides a strong evidence that microcirculation is coupled with macrocirculation not only in terms of structural but also functional parameters.

Subclinical macroangiopathic target organ damage in type 1 diabetes mellitus patients.

PURPOSE: We have summarized key studies regarding the assessment of subclinical macroangiopathic target organ damage (TOD) in type 1 diabetes mellitus (T1DM). RESULTS: Although chronic complications resulting from hyperglycemia, in particular macroangiopathies, are still the first cause of death in T1DM, there has been growing recognition of the role of hypoglycemia in cardiovascular morbidity and mortality. Subclinical TOD diagnosis ensures early implementation of the complex management aiming at either partial reversal of these complications or at least its downturn. To better identify patients with early TODs, several non-invasive diagnostic techniques are employed, including the ultrasonographic assessment of the intima-media thickness (IMT), computed tomography (CT) for coronary artery calcium (CAC) scores, and pulse wave velocity (PWV) measurement for arterial stiffness evaluation. Various studies reported that T1DM patients present an increased IMT. An increasing IMT fairly correlates with the cardiovascular (CV) events risk even after the adjustment to age, diabetes duration, quality of glucose control as well as the presence of hypertension, and chronic complications. Another, well established marker of the organ damage - CAC score is recommended by ACC/AHA guidelines to assess the overall CV risk in T1DM. Also, the arterial stiffness evaluation with PWV may further improve CV risk prediction, which has been reported in multiple studies including the Framingham Heart Study. CONCLUSIONS: There is shortage of data from prospective studies which could confirm the benefits of early treatment initiation based on the presence of the subclinical organ damage in T1DM. Most evidence comes from T2DM trials, where effective preventive measures were identified i.e.: smoking cessation, reasonable blood glucose control, efficacious hypertension treatment, and dyslipidemia management, as well as renoprotection. There is still a field for further research to see if routine assessment of asymptomatic vascular damage and early implementation of aggressive treatment would reduce mortality excess from CVD in T1DM.

Lumen narrowing and increased wall to lumen ratio of retinal microcirculation are valuable biomarkers of hypertension-mediated cardiac damage.

Purpose: In the course of hypertension, left ventricular hypertrophy and diastolic dysfunction develop very often and may progress toward heart failure. The aim of the study was to analyze the relationship between abnormalities of retinal microcirculation and cardiac damage defined as left ventricular hypertrophy and/or diastolic dysfunction.Materials and methods: The study comprised 88 patients with essential hypertension. The group was divided into two subgroups: hypertensives without cardiac damage (n = 55) and with cardiac damage (n = 33). Control group comprised 32 normotensive subjects. Scanning laser Doppler flowmetry was used to evaluate retinal microcirculation. Echocardiography was used to assess cardiac damage.Results: Lumen diameter of retinal arterioles was significantly smaller in patients with cardiac damage vs. controls (77 vs. 84 µm, p = 0.02). Additionally, there was an evident trend with respect to lumen diameter (LD) across all three studied subgroups; i.e.: the smallest dimeters were present in cardiac damage patients, moderate size in hypertensives' without cardiac damage, and the largest diameters in healthy controls (pfor trend < 0.01). Lumen diameter was inversely correlated with cardiac intraventricular septum diameter (R = -0.25, p = 0.02), left ventricular mass (R = -0.24, p = 0.02), and left atrial volume (R = -0.22, p = 0.04). Wall to lumen ratio was associated with intraventricular septum diameter (R = 0.21, p = 0.044) and left atrial volume (R = 0.21, p = 0.045). In multivariable regression analysis, lumen diameter was independently associated with intraventricular septum diameter (ß = -0.05, p = 0.03), left ventricular mass (ß = -1.15, p = 0.04), and left atrial volume (ß = -0.42, p = 0.047); wall to lumen ratio was independently associated with intraventricular septum diameter (ß = 3.67, p = 0.02) and left atrial volume (ß = 30.0, p = 0.04).Conclusions: In conclusion, retinal arterioles lumen diameter and wall to lumen ratio were independent biomarkers of cardiac damage. Retinal examination performed by means of scanning laser Doppler flowmetry might be a valuable tool to improve cardiovascular risk stratification of hypertensive patients.

The accuracy of SpaceLabs 90207 in blood pressure monitoring in patients with atrial fibrillation.

PURPOSE: Irregular heart rhythm in the course of atrial fibrillation (AFib) results in lower blood pressure (BP) measurements reproducibility which is further limited by various BP-monitors used. Therefore the aim of our study was to estimate accuracy of oscillometric BP measurement (SpaceLabs 90207) with reference to mercury manometer-based readings. MATERIAL AND METHODS: Study was performed in 47 hemodynamically stable patients aged 63 ± 12 yo with paroxysmal or persistent AFib, at baseline. Patients were reassessed within one week after effective cardioversion (SR; n = 29). BP was measured using Y-tube connection allowing for simultaneous measurements on the same arm with SpaceLabs 90207 and referral method. Mean values were tested with paired t-tests. Additionally, concordance correlation coefficient (ρc) and Bland-Altman plots were assessed. Results were confronted with AAMI, and ESH-IP criteria. RESULTS: Both during arrhythmia and sinus rhythm diastolic BP differed significantly (Δ = 4.6 ± 6.0 mm Hg, p < .001 and 2.1 ± 4.0 mm Hg, p < .001; for AFib, and SR, respectively), which was not the case for systolic BP. The ρc during arrhythmia equaled 0.89, and 0.75 for systolic and diastolic BP, respectively, which further improved while SR (0.96 and 0.89, respectively). Results confronted against AAMI and ESH-IP showed that all criteria were met except for one (60% vs. required 65% of paired differences of less than 5 mm Hg) during AFib. CONCLUSIONS: The direct comparisons of BP readings allowed to conclude that diastolic blood pressure tended to be slightly overestimated when assessed with SpaceLabs 90207 in patients with both, AFib and SR, which was not a case for systolic BP. When the results were confronted with available validation protocols requirements, all referral criteria were met except for one. Taken together, our results suggest acceptable BP readings dispersion of SpaceLabs 90207 in BP monitoring of patients with both AFib and SR.

Insufficiency of the zona glomerulosa of the adrenal cortex and progressive kidney insufficiency following unilateral adrenalectomy - case report and discussion.

BACKGROUND: Primary aldosteronism (PA) is the most common cause of secondary hypertension and bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) seem to be the most common causes of PA. Unilateral adrenalectomy (UA) is the preferred treatment for APA, although the benefits are still difficult to assess. CASE REPORT: We present a case report of a 69-year old man with a 30 year history of hypertension and probably long-standing PA due to APA, with typical organ complications. Since repeated abdominal CT scans were equivocal, not showing radiological changes characteristic for PA, the diagnosis of APA was delayed and was only finally confirmed by adrenal venous sampling which demonstrated unilateral aldosteronism. The patient underwent UA, complicated by mineralocorticoid deficiency syndrome and increased creatinine and potassium levels. At 12 months follow-up the patient still had hyperkalemia and was fludrocortisone dependent. CONCLUSIONS: Older patients and patients with long-lasting PA who are treated with UA may demonstrate deterioration of renal function and develop transient or persistent insufficiency of the zona glomerulosa of the remaining adrenal gland necessitating fludrocortisone supplementation. Transient hyperkalemia may be observed following UA as a result of the prolonged effects of aldosterone antagonists and/or transient mineralocorticoid/glucocorticoid insufficiency. Additionally, the level of progression of chronic kidney disease after UA is difficult to predict. There likely exists a group of patients who might paradoxically have higher cardiovascular risk due to significant deterioration in kidney function not only resulting from the removal of the aldosterone induced glomerular hyperfiltration phenomenon. Identification of such a group requires further detailed investigation.

Prevalence and distribution of left ventricular diastolic dysfunction in treated patients with long-lasting hypertension.

BACKGROUND: Although the presence of sub-clinical left ventricular diastolic dysfunction (LVDD) increases cardiovascular risk, the current ESH/ESC guidelines do not include the presence of this condition in the list of target organ damage or cardiovascular risk charts dedicated to the hypertensive population. Several conditions may predict the LVDD occurrence, however, clustering of these factors with hypertension makes the relationship less clear. Therefore, the aim of this study was to evaluate both the occurrence and the severity of diastolic dysfunction in a large cohort of treated hypertensives. METHODS: We retrospectively analyzed records of 610 hypertensive participants of the CARE NORTH Study who consented to echocardiography and were free of overt cardiovascular disease. Mean age was 54.0 ± 13.9 years (mean ± SD), BMI 29.7 ± 4.8 kg/m2. The exclusion criteria were: established heart failure, LVEF <45%, coronary revascularization, valvular defect, atrial fibrillation, or stroke. The staging of LVDD was based on comprehensive transthoracic echocardiographic measurements. RESULTS: 49.7% percent of the patients had normal diastolic function (38.8% vs. 59.0%, females (F) vs. males (M), respectively; p < .001). Grade 1 LVDD was documented in 24.4% (27.8% and 21.6%; F and M; p = .08) and grade 2 LVDD in 19.3% (24.9% and 14.6%; F and M; p = .001) of the patients. None were diagnosed with grade 3 LVDD. In the logistic regression model, female sex, advancing age, obesity status, established diabetes mellitus, higher 24-hour SBP, and increasing LVMI were identified as the independent variables increasing the odds for the presence of LVDD, whereas blood-lowering therapy attenuated the risk. CONCLUSIONS: There is an unexpectedly high prevalence of different forms of diastolic dysfunction in treated hypertensive patients who are free of overt cardiovascular disease.

Modelling of subarachnoid space width changes in apnoea resulting as a function of blood flow parameters.

During apnoea, the pial artery is subjected to two opposite physiological processes: vasoconstriction due to elevated blood pressure and vasorelaxation driven by rising pH in the brain parenchyma. We hypothesized that the pial artery response to apnoea may vary, depending on which process dominate. Apnoea experiments were performed in a group of 19 healthy, non-smoking volunteers (9 men and 10 women). The following parameters were obtained for further analysis: blood pressure, the cardiac (from 0.5 to 5.0Hz) and slow (<0.5Hz) components of subarachnoid space width, heart rate, mean cerebral blood flow velocity in the internal carotid artery, pulsatility and resistivity index, internal carotid artery diameter, blood oxygen saturation and end-tidal carbon dioxide. The experiment consisted of three apnoeas, sequentially: 30s, 60s and maximal apnoea. The breath-hold was separated for 5minute rest. The control process is sophisticated, involving internal cross-couplings and cross-dependences. The aim of work was to find a mathematical dependence between data. Unexpectedly, the modelling revealed two different reactions, on the same experimental procedure. As a consequence, there are two subsets of cardiac subarachnoid space width responses to breath-hold in humans. A positive cardiac subarachnoid space width change to apnoea depends on changes in heart rate and cerebral blood flow velocity. A negative cardiac subarachnoid space width change to apnoea is driven by heart rate, mean arterial pressure and pulsatility index changes. The described above two different reactions to experimental breath-hold provides new insights into our understanding of the complex mechanisms governing the adaptation to apnoea in humans. We proposed a mathematical methodology that can be used in further clinical research.

Randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome: the ALL-VASCOR study protocol.

INTRODUCTION: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality. METHODS AND ANALYSIS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland. ETHICS AND DISSEMINATION: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences. PROTOCOL VERSION NUMBER: 01-15 November 2022. TRIAL REGISTRATION NUMBER: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.

Assessing Machine Learning for Diagnostic Classification of Hypertension Types Identified by Ambulatory Blood Pressure Monitoring.

Background: Inaccurate blood pressure (BP) classification results in inappropriate treatment. We tested whether machine learning (ML), using routine clinical data, can serve as a reliable alternative to ambulatory BP monitoring (ABPM) in classifying BP status. Methods: This study employed a multicentre approach involving 3 derivation cohorts from Glasgow, Gdansk, and Birmingham, and a fourth independent evaluation cohort. ML models were trained using office BP, ABPM, and clinical, laboratory, and demographic data, collected from patients referred for hypertension assessment. Seven ML algorithms were trained to classify patients into 5 groups, named as follows: Normal/Target; Hypertension-Masked; Normal/Target-White-Coat (WC); Hypertension-WC; and Hypertension. The 10-year cardiovascular outcomes and 27-year all-cause mortality risks were calculated for the ML-derived groups using the Cox proportional hazards model. Results: Overall, extreme gradient boosting (using XGBoost open source software) showed the highest area under the receiver operating characteristic curve of 0.85-0.88 across derivation cohorts, Glasgow (n = 923; 43% female; age 50.7 ± 16.3 years), Gdansk (n = 709; 46% female; age 54.4 ± 13 years), and Birmingham (n = 1222; 56% female; age 55.7 ± 14 years). But accuracy (0.57-0.72) and F1 (harmonic mean of precision and recall) scores (0.57-0.69) were low across the 3 patient cohorts. The evaluation cohort (n = 6213; 51% female; age 51.2 ± 10.8 years) indicated elevated 10-year risks of composite cardiovascular events in the Normal/Target-WC and the Hypertension-WC groups, with heightened 27-year all-cause mortality observed in all groups, except the Hypertension-Masked group, compared to the Normal/Target group. Conclusions: ML has limited potential in accurate BP classification when ABPM is unavailable. Larger studies including diverse patient groups and different resource settings are warranted.

Contexte: Les erreurs dans la classification des valeurs de la pression artérielle (PA) entraînent une inadéquation du traitement. Nous avons tâché de déterminer si l'apprentissage machine, à l'aide de données cliniques routinières, constituait une solution de rechange fiable à la surveillance ambulatoire de la PA pour définir le statut de la PA. Méthodologie: Cette étude a utilisé une approche multicentrique incluant trois cohortes de dérivation de Glasgow, Gdansk et Birmingham, et une quatrième cohorte d'évaluation indépendante. Les modèles d'apprentissage machine ont été développés en analysant les données démographiques, les valeurs de la PA mesurée au cabinet, les données relatives à la surveillance ambulatoire de la PA et aux épreuves de laboratoire recueillies auprès de patients adressés pour une évaluation de l'hypertension. Sept algorithmes d'apprentissage machine ont été appliqués pour classer les patients en cinq groupes : Normale/Cible; Hypertension-Masquée; Normal/Cible-Blouse blanche; Hypertension-Blouse blanche; Hypertension. Les événements cardiovasculaires sur 10 ans et le risque de mortalité toutes causes confondues sur 27 ans ont été calculés dans les groupes dérivés de l'apprentissage machine à l'aide d'un modèle de risques proportionnels de Cox. Résultats: D'une manière générale, l'amplification de gradient extrême (à l'aide du logiciel ouvert XGBoost) a mis en évidence l'aire sous la courbe de la fonction d'efficacité du récepteur (courbe ROC pour Receiver Operating Characteristic) la plus haute, soit 0,85 à 0,88, pour toutes les cohortes de dérivation : Glasgow (n = 923; 43 % de femmes; âge : 50,7 ± 16,3 ans); Gdansk (n = 709; 46 % de femmes; âge : 54,4 ± 13 ans); Birmingham (n = 1 222; 56 % de femmes; âge : 55,7 ± 14 ans). La précision (0,57 ­ 0,72) et le score F1 (moyenne harmonique de la précision et du rappel) (0,57 ­ 0,69) ont été faibles dans les trois cohortes de patients. La cohorte d'évaluation (n = 6 213; 51 % de femmes; âge : 51,2 ± 10,8 ans) a indiqué un risque d'événements cardiovasculaires composites sur 10 ans élevé dans les groupes Normale/Cible-Blouse blanche et Hypertension-Blouse blanche, tandis qu'une hausse de la mortalité toutes causes confondues sur 27 ans a été observée dans tous les groupes, sauf dans le groupe Hypertension-Masquée, comparativement au groupe Normale/Cible. Conclusions: Le potentiel d'exactitude de la classification de la PA à l'aide de l'apprentissage machine lorsque la surveillance ambulatoire de la PA n'est pas possible est limité. Des études de plus grande envergure portant sur des groupes de patients et des niveaux de ressources diversifiés s'imposent.

Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries.

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease.

Revelations about carotid body function through its pathological role in resistant hypertension.

Much recent attention has been given to the carotid body because of its potential role in cardiovascular disease states. One disease, neurogenic hypertension, characterised by excessive sympathetic activity, appears dependent on carotid body activity that may or may not be accompanied by sleep-disordered breathing. Herein, we review recent literature suggesting that the carotid body acquires tonicity in hypertension. We predict that carotid glomectomy will be a powerful way to temper excessive sympathetic discharge in diseases such as hypertension. We propose a model to explain that signalling from the 'hypertensive' carotid body is tonic, and hypothesise that there will be a sub-population of glomus cells that channel separately into reflex pathways controlling sympathetic motor outflows.

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation.

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

Vascular Aging and Damage in Patients with Iron Metabolism Disorders.

Vascular aging is a physiological, multifactorial process that involves every type of vessel, from large arteries to microcirculation. This manifests itself as impaired vasomotor function, altered secretory phenotype, deteriorated intercellular transport function, structural remodeling, and aggravated barrier function between the blood and the vascular smooth muscle layer. Iron disorders, particularly iron overload, may lead to oxidative stress and, among other effects, vascular aging. The elevated transferrin saturation and serum iron levels observed in iron overload lead to the formation of a non-transferrin-bound iron (NTBI) fraction with high pro-oxidant activity. NTBI can induce the production of reactive oxygen species (ROS), which induce lipid peroxidation and mediate iron-related damage as the elements of oxidative stress in many tissues, including heart and vessels' mitochondria. However, the available data make it difficult to precisely determine the impact of iron metabolism disorders on vascular aging; therefore, the relationship requires further investigation. Our study aims to present the current state of knowledge on vascular aging in patients with deteriorated iron metabolism.

Predictors of Mortality in Hemodialyzed Patients after SARS-CoV-2 Infection.

INTRODUCTION: The determinants of COVID-19 mortality are well-characterized in the general population. Less numerous and inconsistent data are among the maintenance hemodialysis (HD) patients, who are the population most at risk of an unfavorable prognosis. METHODS: In this retrospective cohort study we included all adult HD patients from the Pomeranian Voivodeship, Poland, with laboratory-confirmed SARS-CoV-2 infection hospitalized between 6 October 2020 and 28 February 2021, both those who survived, and also those who died. Demographic, clinical, treatment, and laboratory data on admission, were extracted from the electronic medical records of the dedicated hospital and patients' dialysis unit, and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with 3-month all-cause mortality. RESULTS: The 133 patients (53.38% males) aged 73.0 (67-79) years, with a median duration of hemodialysis of 42.0 (17-86) months, were included in this study. At diagnosis, the majority were considered to have a mild course (34 of 133 patients were asymptomatic, another 63 subjects presented mild symptoms), while 36 (27.07%) patients had low blood oxygen saturation and required oxygen supplementation. Three-month mortality was 39.08% including an in-hospital case fatality rate of 33.08%. Multivariable logistic regression showed that the frailty clinical index of 4 or greater (OR 8.36, 95%CI 1.81-38.6; p < 0.01), D-Dimer of 1500 ng/mL or greater (6.00, 1.94-18.53; p < 0.01), and CRP of >118 mg/L at admission (3.77 1.09-13.01; p = 0.04) were found to be predictive of mortality. CONCLUSION: Very high 3-month all-cause mortality in hospitalized HD patients was determined mainly by frailty. High CRP and D-dimer levels upon admission further confer mortality risk.

COVID-19 vaccination reduces mortality in patients on maintenance hemodialysis.

Patients with chronic kidney disease on maintenance hemodialysis (HD) have a very high risk of death in the course of COVID-19. The aim of the study was to assess the effectiveness of COVID-19 vaccination to reduce the incidence of COVID-19 and the fatality rate in HD patients. A retrospective registry-based cohort study was performed in all HD adult patients in the Pomeranian Voivodeship. Vaccinations were carried out from January to April 2021 with mRNA vaccines, either BNT162b2 or mRNA-1273 with two-dose schedule. In the first analysis (2nd pandemic wave), 1,160 unvaccinated patients were included (59.7% males, 25.7% diabetic). In the second analysis (4th pandemic wave), 1,131 (59.4% male, 30.7% diabetic) individuals were included, 1,042 (92.13%) were fully vaccinated. Three hundred and fifteen HD patients (27.2%) were COVID-19 positive during the 2nd wave, and 6.9% (78/1,131) during the 4th wave. Within the fully vaccinated patients of the 4th wave, 60 were COVID-19 positive, 5.8 vs. 20.2% of unvaccinated COVID-19 positive patients in 2nd wave, respectively. COVID-19 incidence rate ratio (IRR) was 0.21 (4th wave-vaccinated vs. 2nd wave-unvaccinated) indicating a 79% reduction. The IRR between vaccinated and unvaccinated patients of the 4th wave was 0.28 in favor of vaccinated patients with 72% reduction. In the 2nd wave, 93 patients died as a result of COVID-19 (fatality rate: 29.5%). The fatality rate of fully vaccinated patients during the 4th wave was 6.7% (p = 0.004), while the fatality rate in the 4th wave within unvaccinated patients accounted for 11.1%. Significant clinical effectiveness of COVID-19 vaccination was demonstrated in a multicenter study in HD patients.

Facing the Challenge of Lowering Blood Pressure and Cholesterol in the Same Patient: Report of a Symposium at the European Society of Hypertension.

A symposium held at the 29th European Meeting on Hypertension and Cardiovascular Protection in Milan, Italy, discussed the potential impact and long-term benefits of early active management of cardiovascular disease (CVD) risk in patients with hypertension, and potential barriers to this strategy. Hypertension often aggregates with other cardiovascular risk factors, exponentially increasing morbidity and mortality. While effective therapies to treat hypertension exist, a substantial number of patients still experience major cardiovascular events. Two major issues account for these disappointing results: interventions initiated too late in the disease trajectory and lack of effective translation of the research findings into daily clinical practice. Results from genetic studies suggest that lifetime exposure to lower blood pressure (BP) and cholesterol levels due to protective gene mutations, can provide greater cardiovascular benefits than middle-/late-age interventions. Clinical guidelines suggest adding statins to BP-lowering therapies for further cardiovascular benefits in most hypertensive patients; however, real-world data show that physicians' compliance with these recommendations and patients' adherence to BP- and lipid-lowering treatments remain poor, resulting in poor risk factor control and an increased risk of adverse outcomes. The use of single-pill combinations (SPC) can partially mitigate these issues, as they are associated with increased patient adherence and improved BP control. Treatment with SPC has been recommended in the European Hypertension Guidelines, but optimization of the total CVD risk may need adoption of more ambitious treatment strategies aimed to deliver single pills that control multiple CVD risk factors. Amlodipine, perindopril and atorvastatin have been shown to improve BP and lipid levels to a great extent when given separately, and this combination has also been shown to improve cardiovascular outcomes. Overall, early intervention in patients with hypertension with use of an effective, high-intensity cardiovascular risk reduction regimen and attention to medication adherence through reducing pill burden are likely to result in optimal outcomes.

The use of single-pill combinations as first-line treatment for hypertension: translating guidelines into clinical practice.

: The 2008 European Society of Cardiology/European Society of Hypertension guidelines recommend the first-line prescription of two antihypertensive drugs in single-pill combinations (SPCs), also known as fixed-dose combinations, for the treatment of most patients with hypertension. This recommendation is based on a large amount of data, which shows that first-line treatment with SPCs supports reaching blood pressure targets rapidly and reducing cardiovascular outcome risk while keeping the therapeutic strategies as simple as possible and fostering adherence and persistence. As this approach constitutes a big shift from the stepped-care approaches that have been dominant for many years, practicing physicians have expressed concerns about using SPCs as first-line agents. In this review, we will discuss the barriers to the uptake of this recommendation. We will also offer suggestions to reduce the impact of these barriers and address specific concerns that have been raised.