Revealing the nature of cardiovascular disease using DERGA, a novel data ensemble refinement greedy algorithm.

BACKGROUND: The study aimed to determine the most crucial parameters associated with CVD and employ a novel data ensemble refinement procedure to uncover the optimal pattern of these parameters that can result in a high prediction accuracy. METHODS AND RESULTS: Data were collected from 369 patients in total, 281 patients with CVD or at risk of developing it, compared to 88 otherwise healthy individuals. Within the group of 281 CVD or at-risk patients, 53 were diagnosed with coronary artery disease (CAD), 16 with end-stage renal disease, 47 newly diagnosed with diabetes mellitus 2 and 92 with chronic inflammatory disorders (21 rheumatoid arthritis, 41 psoriasis, 30 angiitis). The data were analyzed using an artificial intelligence-based algorithm with the primary objective of identifying the optimal pattern of parameters that define CVD. The study highlights the effectiveness of a six-parameter combination in discerning the likelihood of cardiovascular disease using DERGA and Extra Trees algorithms. These parameters, ranked in order of importance, include Platelet-derived Microvesicles (PMV), hypertension, age, smoking, dyslipidemia, and Body Mass Index (BMI). Endothelial and erythrocyte MVs, along with diabetes were the least important predictors. In addition, the highest prediction accuracy achieved is 98.64%. Notably, using PMVs alone yields a 91.32% accuracy, while the optimal model employing all ten parameters, yields a prediction accuracy of 0.9783 (97.83%). CONCLUSIONS: Our research showcases the efficacy of DERGA, an innovative data ensemble refinement greedy algorithm. DERGA accelerates the assessment of an individual's risk of developing CVD, allowing for early diagnosis, significantly reduces the number of required lab tests and optimizes resource utilization. Additionally, it assists in identifying the optimal parameters critical for assessing CVD susceptibility, thereby enhancing our understanding of the underlying mechanisms.

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Prevalence, awareness, and control of hypertension in Greece before and after the COVID-19 pandemic: May Measurement Month survey 2019-2022.

OBJECTIVE: The COVID-19 pandemic had an adverse impact on several cardiovascular risk factors. This study investigated the prevalence, awareness and treatment of hypertension in Greece before and after the pandemic. Data were collected in the context of the May Measurement Month (MMM) global survey initiated by the International Society of Hypertension. METHODS: Adult volunteers (age ≥ 18 years) were recruited through opportunistic screening in public areas across cities in Greece in 2019 and 2022. Medical history and triplicate sitting blood pressure (BP) measurements were taken using validated automated upper-arm cuff devices. The data were uploaded to the international MMM cloud platform. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic ≥90 mm Hg and/or self-reported use of drugs for hypertension. The same threshold was used to define uncontrolled BP in treated individuals. RESULTS: Data from 12,080 adults were collected (5,727/6,353 in MMM 2019/2022; men 46/49%, p < 0.01; mean age 52.7 ± 16.6/54.8 ± 16.2, p < 0.001; smokers, 24.7/30.5, p < 0.001; diabetics 12/11.5%, p = NS; cardiovascular disease 5/5.8%, p = NS). The prevalence of hypertension was 41.6/42.6% (MMM 2019/2022, p = NS), with 21.3/27.5% of individuals with hypertension being unaware of their condition (p < 0.001), 5.6/2.4% aware untreated (p < 0.001), 24.8/22.1% treated uncontrolled (p < 0.05), and 48.3/47.8% treated controlled (p = NS). CONCLUSION: In Greece, the COVID-19 pandemic did not appear to affect the prevalence and control of hypertension; however, the rate of undiagnosed hypertension was higher after the pandemic. National strategies need to be implemented for the early detection and optimal management of hypertension in the general population in Greece.

Management of hypertensive disorders in pregnancy: a Position Statement of the European Society of Hypertension Working Group 'Hypertension in Women'.

Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group 'Hypertension in Women' of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research.

Short-Term Variability of Both Brachial and Aortic Blood Pressure is Increased in Patients with Immune-mediated Chronic Inflammation.

INTRODUCTION: Blood pressure (BP) variability (BPV) has emerged as an indicator of subclinical organ damage and an independent predictor of cardiovascular disease (CVD) morbidity and mortality in high-risk populations. AIM: We aimed to assess short-term variability of both brachial and aortic BP in psoriasis, a common immune-mediated inflammatory disorder characterized by increased CVD risk. METHODS: Psoriasis patients and non-psoriasis individuals had their BP assessed throughout a 24 h period (Mobil-O-Graph device). Brachial and aortic BPV during the 24 h and the respective daytime and nighttime periods was calculated from relevant ambulatory BP profiles. In-house software was applied to automatically calculate average real variability (ARV) of brachial and aortic systolic (bSBP, aSBP) and diastolic BP (bDPB, aDBP), and the weighted standard deviation (wSD) of 24 h bSBP/aSBP. 24 h pulse wave velocity (PWV) and augmentation index (AIx) were used as widely applied markers of arterial stiffness. RESULTS: Psoriasis patients (n = 74) presented increased ARV of 24 h and daytime bSBP/aSBP, and increased ARV of 24 h and daytime bDBP/aDBP, compared to controls (n = 40). PWV and AIx correlated with ARV of 24 h bSBP/aSBP, daytime bSBP/aSBP, while PWV further correlated with ARV of nighttime aSBP. The observed associations with PWV, yet not AIx, with indices of BPV remained significant after adjusting for CVD risk factors. CONCLUSIONS: This is the first study reporting increased 24 h variability of both brachial and aortic BP in psoriasis. The association of short-term BPV with arterial stiffness implies a potential role of BPV in terms of CVD risk stratification in patients with chronic immune-mediated inflammation.

Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis.

OBJECTIVES: Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. METHODS: We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. RESULTS: We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. CONCLUSION: Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 µm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

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.

Clinical Significance of Nocturnal Hypertension and Nighttime Blood Pressure Dipping in Hypertension.

PURPOSE OF REVIEW: This narrative review article aims to discuss more recent evidence, current challenges, and future perspectives regarding the clinical importance of nocturnal hypertension and nighttime blood pressure dipping, with particular reference to diagnosis, prognostic value, and therapeutic approach. RECENT FINDINGS: The importance of nighttime blood pressure and nighttime blood pressure dipping has been demonstrated in decades. Increased nighttime blood pressure has been acknowledged as an unfavorable clinical trait. However, more recent evidence suggests that the abolishment of normal circadian blood pressure rhythm is not always a solid predictor of adverse cardiovascular events and needs to be interpreted in the light of each patients' individual characteristics. Physicians treating hypertensive patients with adverse nighttime blood pressure profiles often face the dilemma of chronotherapy. This has been a blurred field for years, yet very recent evidence from appropriately designed studies attempts to shed light on this puzzling question. As 24-h ambulatory blood pressure monitoring is being increasingly recommended and applied in real-world practice for the diagnosis and monitoring of hypertension, information on nighttime blood pressure and nocturnal dipping profile is collected but is not always easy to interpret.

Impact of the Level of Adherence to the DASH Diet on Blood Pressure: A Systematic Review and Meta-Analysis.

Introduction: the objective of our study was to systematically review the current literature and perform a meta-analysis to evaluate the effect of the level of adherence to the DASH diet on blood pressure. Methods: The identification of relevant studies, data extraction and critical appraisal of the included studies were performed independently by two reviewers. A random-effects model was employed to synthesize the available evidence using the standardized mean difference (SMD) as the appropriate effect size. Results: A total of 37 and 29 articles were included in the qualitative and quantitative analysis, respectively. The pooled effect for systolic blood pressure was SMD = -0.18 (95%CI: -0.32 to -0.04; I2 = 94%; PI: -0.93 to 0.57) and for diastolic blood pressure it was SMD = -0.13 (95%CI: -0.19 to -0.06; I2 = 94%; PI: -0.42 to 0.17). Conclusions: Our findings showed that greater adherence to the DASH diet has a beneficial effect on blood pressure compared to the lowest adherence. Increased compliance with DASH diet recommendations might also have a positive effect on cardiometabolic factors and overall health status. Future studies should aim to standardize the tools of adherence to the DASH diet and utilize rigorous study designs to establish a clearer understanding of the potential benefits of the level of adherence to the DASH diet in blood pressure management.

Circulating microvesicles across a population with various degree of cardiovascular burden are associated with systolic blood pressure.

Circulating microvesicles (MVs) have been studied in heterogeneous, divergent, and rather small patient populations with cardiovascular risk . Therefore, we measured endothelial (EMVs), platelet (PMVs) and erythrocyte (RMVs) MVs in patients with divergent cardiovascular risk. We then compared them to coronary artery disease (CAD) and healthy subjects and identified independent MVs' predictors. We enrolled consecutive patients from our Cardiology, Hypertension, Diabetic, Rheumatic, and Nephrology Outpatient Units with MVs measurements. Central blood pressure (BP) was measured by either applanation tonometry or Mobil-O-graph device, while MVs by a standardized flow cytometry protocol. We studied 369 participants with increased cardiovascular risk: 63 with high cardiovascular risk (47 diabetes mellitus type II/DM and 16 end-stage renal disease/ESRD), 92 with chronic inflammatory disorders and 73 with untreated essential hypertension/UEH. We further included 53 subjects with CAD and 87 otherwise healthy individuals. All MVs were lower in patients with increased cardiovascular risk compared to CAD, showing predictive value with high sensitivity and specificity. Furthermore, PMVs and EMVs were increased in patients with cardiovascular risk compared to healthy individuals. DM and ESRD patients had increased EMVs versus UEH and chronic inflammatory disorders. In the whole study population, RMVs were associated only with history of essential hypertension. In multivariate analysis, systolic BP predicted PMVs. Aage, systolic BP, and DM predicted EMVs. In a large population of patients with divergent cardiovascular risk, MVs are independently associated with systolic blood pressure.

Adherence to the DASH Diet and Risk of Hypertension: A Systematic Review and Meta-Analysis.

The aim of this study was to assess the effect of the level of adherence to the DASH diet on hypertension risk by conducting a systematic review and meta-analysis. A systematic literature search was performed. Two independent investigators performed the study selection, data abstraction, and assessment of the included studies. The meta-analysis was performed separately with the adjusted hazard (HR) or incident rate ratios (IRR) and the odds ratios (OR) of the highest compared to the lowest DASH diet adherence scores using a random effects model. A total of 12 studies were included in the qualitative and quantitative synthesis. When cohort studies reporting HR were pooled together, high adherence to the DASH diet was associated with a lower risk of hypertension (HR: 0.81, 95% CI 0.73-0.90, I2 = 69%, PI 0.61-1.08) compared to the low adherence. When cross-sectional studies reporting OR were combined, high adherence to the DASH diet was also related to a lower risk of hypertension (OR: 0.80, 95% CI 0.70-0.91, I2 = 81%, PI 0.46-1.39). The findings suggest that high adherence to the DASH diet has a positive effect on reducing hypertension risk compared to low adherence. These data strengthen and are in line with all hypertension guidelines, indicating that lifestyle changes should start early even in populations with normal blood pressure.

Circulating levels of galectin-3 and coronary microvascular perfusion in rheumatoid arthritis patients with suppressed inflammation.

OBJECTIVE: Cardiovascular manifestations are the leading cause of mortality in rheumatoid arthritis (RA). Galectin-3, a lectin protein with major role in cellular, inflammatory, and fibrotic processes, has been introduced as a novel cardiac biomarker. We hypothesized that patients with RA present increased levels of galectin-3, and investigated potential associations with arterial stiffness and coronary microvascular dysfunction. METHODS: This cross-sectional study enrolled RA patients and non-RA individuals without cardiovascular comorbidities. Galectin-3 and high-sensitivity C-reactive protein (hsCRP) were measured with enzyme-linked immunosorbent assay (ELISA) in serum samples. Subendocardial viability ratio (SEVR), an index of microvascular myocardial perfusion, and pulse wave velocity (PWV), the gold-standard measure of vascular stiffness, were estimated with applanation tonometry. RESULTS: Cardiovascular risk factors and hsCRP were comparable between patients (n = 24) and controls (n = 24). However, galectin-3 was increased [6.9 (6.7) vs 4.6 (4.7)] ng/dl, p = 0.015], and coronary microvascular perfusion was decreased (142.6 ± 22.8 vs 159.7 ± 23.2%, p = 0.028) in RA patients compared to controls, whereas PWV did not significantly differ. Galectin-3 correlated with both PWV and SEVR in univariate analysis. However, after adjustment for cardiovascular risk factors and subclinical inflammation, these associations were rendered non-significant. CONCLUSION: Galectin-3 appears increased in RA, even among patients with suppressed inflammation in the absence of cardiovascular comorbidities. The observed association of galectin-3 with coronary microvascular perfusion in our study was non-significant after adjustment for cardiovascular risk factors and inflammation. The potential role of galectin-3 as a cardiac biomarker in RA warrants further investigation. Key Points • Galectin-3 has emerged as a novel cardiac biomarker but remains understudied in RA. • Patients with RA present elevated levels of galectin-3 and impaired coronary microvascular perfusion compared to non-RA individuals. • These differences were observed in patients with suppressed inflammation, even in the absence of CVD. • The association of galectin-3 with coronary microvascular impairment in RA warrants further investigation.

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.

Assessing skin microcirculation in patients at cardiovascular risk by using laser speckle contrast imaging. A narrative review.

Skin tissue holds a prominent role in microcirculatory research as an easily accessible vascular bed for the noninvasive evaluation of microvascular function. Skin microvascular changes have been associated to alterations in distinct target organs and vascular beds, reinforcing the hypothesis that skin microcirculation can be used as a model of generalized microvascular function. In addition, skin microvascular dysfunction has been documented in cardiovascular disease and patients of increased cardiovascular risk where it has been associated with multiple cardiovascular risk factors, rendering it a candidate surrogate marker of vascular damage. Laser speckle contrast imaging (LSCI) is a noninvasive, dynamic laser technique that allows assessment of skin microvascular function (SMF) by obtaining two-dimensional maps of the skin perfusion in real time with high spatial and temporal resolution and, most importantly, with the highest reproducibility compared to other laser methods. An ever-increasing number of studies using LSCI is confirming evidence of impaired SMF in several cardiovascular risk groups, therefore expanding its application in microvascular research and showing its potential clinical utility. This review attempts to present the growing importance of SMF in cardiovascular research and the emergence of LSCI technique as a robust imaging modality with a promising role to explore skin microvascular physiology. After a short description of the relevant technique and its main principle of function, we have also opted to present the most up to date studies using LSCI for the investigation of SMF in patients with cardiovascular disease as well as various groups of increased cardiovascular risk.

Microvascular and Endothelial Dysfunction in Prediabetes.

Prediabetes is a significant metabolic status since there is high potential for future progression of diabetes mellitus (DM). People with prediabetes are at increased risk of cardiovascular disease (CVD) and mortality. Endothelial and microvascular dysfunction is considered a key step towards the development and progression of CVD. Importantly, endothelial and microvascular dysfunction can be detected and monitored using non-invasive procedures in peripheral organs and tissues, including the retina, kidney, skin and skeletal muscle. Structural and functional alterations of the microvasculature have been consistently documented in the above microvascular beds in patients with diabetes mellitus. In contrast, such alterations remain understudied in prediabetes, but are currently receiving attention as markers of subclinical and future CVD. The aim of this review is to summarize available evidence regarding the presence of subclinical microvascular and endothelial dysfunction in prediabetes and their impact on cardiovascular risk.

Association between ambulatory blood pressure monitoring patterns with cognitive function and risk of dementia: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis is to investigate whether nocturnal blood pressure fall, expressed by dipping patterns according to 24 h ambulatory blood pressure monitoring (ABPM), is associated with abnormal cognitive function (cognitive impairment or dementia). METHODS: We systematically searched PubMed, Embase, and Cochrane databases to identify original articles through December 2022. We included any study with at least ten participants reporting on all-cause dementia or cognitive impairment incidence (primary outcome) or validated cognitive tests (secondary outcome) among ABPM patterns. We assessed risk of bias using Newcastle-Ottawa Quality Assessment Scale. We pooled odds ratios (OR) and standardized mean differences (SMD) using random-effect models for primary and secondary outcome, respectively. RESULTS: In the qualitative synthesis, 28 studies examining 7595 patients were included. The pooled analysis of 18 studies showed that dippers had a 51% [OR 0.49(0.35-0.69)] lower risk of abnormal cognitive function and a 63% [OR 0.37(0.23-0.61)] lower risk of dementia alone, compared to non-dippers. Reverse dippers presented an up to sixfold higher risk [OR 6.06(3.15-11.64)] of abnormal cognitive function compared to dippers and an almost twofold higher risk [OR 1.81(1.26-2.6)] compared to non-dippers. Reverse dippers performed worse in global function neuropsychological tests compared with both dippers [SMD - 0.66(- 0.93 to - 0.39)] and non-dippers [SMD - 0.35(- 0.53 to - 0.16)]. CONCLUSION: Dysregulation of the normal circadian BP rhythm, specifically non-dipping and reverse dipping is associated with abnormal cognitive function. Further studies are required to determine potential underlying mechanisms and possible prognostic or therapeutic implications. PROTOCOL REGISTRATION: PROSPERO database (ID: CRD42022310384).