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.

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.

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.

In vitro and in vivo glycemic responses and antioxidant potency of acorn and chickpea fortified gluten-free breads.

Gluten-free (GF) breads, based on rice flour and corn starch (50:50), were fortified with a mixture of acorn flour (ACF) - chickpea flour (CPF) at 30% substitution level of corn starch (i.e., rice flour:corn starch:ACF-CPF 50:20:30) using different flour blends of ACF:CPF at weight ratios of 5:25, 7.5:22.5, 12.5:17.5, and 20:10 in order to improve the nutritional quality and antioxidant potential as well as the glycemic responses of the GF breads; a control GF bread with rice flour:corn starch 50:50 ratio was also prepared. ACF was richer in total phenolic content than CPF, whereas CPF was characterized by higher amounts of total tocopherols and lutein compared to ACF. For both ACF and CPF as well as the fortified breads, the most abundant phenolic compounds were gallic (GA) and ellagic (ELLA) acids as found by HPLC-DAD analysis, while a hydrolysable tannin, valoneic acid dilactone, was also identified and quantified by HPLC-DAD-ESI-MS in high amount in the ACF-GF bread having the highest level of ACF (ACF:CPF 20:10), even though it seemed to decompose during breadmaking, possibly into GA and ELLA. Therefore, the inclusion of these two raw materials as ingredients in GF bread formulations resulted in baked products with enhanced concentrations of such bioactive compounds and higher antioxidant activities, as indicated by three different assays (DPPH, ABTS and FRAP). The extent of glucose release, as evaluated by an in vitro enzymic assay, was negatively correlated (r = -0.96; p = 0.005) with the level of added ACF, and was significantly reduced for all ACF-CPF fortified products when compared with their non-fortified GF counterpart. Furthermore, the GF bread containing a flour mixture of ACP:CPF at a weight ratio of 7.5:22.5, was subjected to an in vivo intervention protocol to assess the glycemic response when consumed by 12 healthy volunteers; in this case, white wheat bread was used as reference food. The glycemic index (GI) of the fortified bread was significantly lower compared to the control GF bread (97.4 versus 159.2, respectively), which along with its lower amount of available carbohydrates and the higher level of dietary fibers, resulted in a significantly reduced glycemic load (7.8 versus 18.8 g per serving of 30 g). The present findings underlined the effectiveness of acorn and chickpea flours in improving the nutritional quality and glycemic responses of fortified GF breads with these flours.

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).

Skin microcirculation dynamics are impaired in patients with rheumatoid arthritis and no cardiovascular comorbidities.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk. Microvascular endothelial dysfunction contributes to the development of vascular injury and subsequent CVD. We hypothesised that RA patients exhibit blunted microvascular reactivity regardless of CVD risk factors and investigated potential associations with coronary microvascular perfusion and surrogate markers of CVD. METHODS: This case-control study recruited RA patients and non-RA individuals in the absence of cardiovascular comorbidities. Skin microvascular reactivity was dynamically assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperaemia protocol. Applanation tonometry was applied to assess subendocardial viability ratio, an index of myocardial microvascular perfusion, and central arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index]. Peripheral arterial stiffness (carotid PWV, ß-stiffness index) and carotid atherosclerosis (intima-media thickness) were assessed with carotid ultrasound software. RESULTS: Skin microvascular responses before and following reperfusion [baseline flux, occlusion flux, time-to-peak, peak magnitude, peak-to-baseline magnitude, baseline cutaneous vascular conductance (CVC), and percentage increase in CVC] were significantly impaired in RA patients (n=35) compared to controls (n=35). Presence of RA independently predicted altered microvascular reactivity in multivariate analysis. Skin microcirculation dynamics significantly correlated with coronary microvascular perfusion and peripheral arterial stiffness, yet not carotid atherosclerosis, even after adjustment for CVD risk factors. CONCLUSIONS: Patients with RA present impaired microvascular reactivity regardless of CVD risk factors at a preclinical stage preceding CVD. Assessment of skin microvascular dysfunction may reflect a state of generalised vasculopathy, including myocardial microvascular abnormalities, and serve as a non-invasive surrogate indicator of CVD risk in RA.

Blunted cerebral oxygenation during exercise in systemic lupus erythematosus patients.

OBJECTIVES: Subclinical brain lesions have been reported in systemic lupus erythematosus (SLE) patients. Advanced neuroimaging techniques have revealed microstructural and microvascular alterations. Most studies examining structural or functional brain abnormalities were performed either at rest or during a mental task. Our study aimed to examine possible differences in cerebral oxygenation during exercise between SLE patients without known neuropsychiatric manifestations and age-matched controls, using near-infrared-spectroscopy (NIRS) and examine possible underlying mechanisms through evaluation of brain derived neurotrophic factor (BDNF) levels. METHODS: The protocol involved a seated rest, a 3-min submaximal (30%) handgrip exercise, and a 3-min recovery. Continuous-NIRS was used to monitor changes in cerebral-oxygenated (O2Hb), de-oxygenated (HHb) and total-haemoglobin (tHb). BDNF levels were measured in serum samples. RESULTS: Twenty-six SLE patients and 27 matched controls were enrolled. No differences were observed in baseline characteristics. During exercise, cerebral-O2Hb increased in both groups. However, SLE patients exhibited a significantly lower average- (1.20 ± 0.89 vs. 2.69 ± 2.46, p=0.001) and peak-O2Hb response (2.89 ± 1.56 vs. 5.83 ± 4.59, p=0.004) compared to controls. Serum BDNF levels were significantly lower in SLE patients compared to controls (p<0.01). CONCLUSIONS: To our knowledge, this is the first study to evaluate cerebral oxygenation during exercise using NIRS in SLE patients compared to age-matched controls. Our data show that SLE patients even without overt neuropsychiatric manifestations exhibit a blunted increase in cerebral-O2Hb during a submaximal exercise stimulus. Examining brain oxygenation during a simple exercise task may assist in identifying patients with early alterations in cerebral function.

Microcirculation dynamics in systemic vasculitis: evidence of impaired microvascular response regardless of cardiovascular risk factors.

OBJECTIVES: Systemic vasculitides (SVs) are a highly inflammatory group of diseases characterized by significant cardiovascular (CV) mortality. Microvascular damage closely linked with accelerated atherosclerosis and thrombosis represents a core pathophysiological mechanism contributing to the excess CV risk of patients with SVs. Skin represents an easily accessible tissue facilitating non-invasive microvascular study. In this study we aimed to investigate microcirculation dynamics and associate them with disease-related factors in patients with SVs. METHODS: We assessed skin microcirculation using laser speckle contrast imaging (LSCI) and vascular reactivity by the post-occlusive reactive hyperaemia (PORH) protocol in a meticulously selected group of patients with SVs without CV disease and compared them to controls, matched for age, sex, BMI and smoking status. RESULTS: Sixty individuals were included in the study, 30 patients and 30 controls. Patients with SVs presented a lower peak magnitude during reperfusion phase (median [interquartile range] 207 [60.1] vs 143.7 [41.0] laser speckle perfusion units, P < 0.001) and lower percentage cutaneous vascular conductance increase (mean (s.d.) 190.0 [49.6]% vs 149.6 [48.9]%, P = 0.002) as compared with controls. Importantly, microvascular damage was correlated with disease duration (P < 0.001, r = -0.563 and P < 0.001, r = 0.442, respectively). CONCLUSION: For the first time we have shown that patients with SVs exhibit impaired microvascular function and blunted reactivity after occlusion, as this was demonstrated by the LSCI technique. Therefore, skin microcirculation may be a useful, non-invasive method in patients with SVs for the early detection of microvascular dysfunction, which is closely related to the high CV risk that these patients bear.

Relationship of 24-h ambulatory blood pressure variability with micro and macrovascular parameters and hypertension status.

OBJECTIVES: Increased blood pressure variability (BPV) has been associated with an increased risk of subclinical organ damage and cardiovascular events, independently of elevated average BP values. We aimed to investigate the association of BPV indices with micro- and macrovascular parameters, some of them not previously studied. METHODS: We evaluated 344 individuals (233 never-treated/newly diagnosed hypertensive and 111 normotensive individuals). BPV was assessed using average real variability (ARV) during 24-h, daytime and night-time ambulatory blood pressure monitoring, and systolic weighted standard deviation (wSD). Retinal microvascular diameter was assessed by nonmydriatic retinal photography. Arterial stiffness was assessed by pulse wave velocity (PWV) and aortic augmentation index (AIx); subendocardial variability ratio (SEVR) was used as an index of myocardial perfusion. Carotid intima-media thickness (cIMT) was measured by ultrasound. Data were analyzed using multiple regression analysis. RESULTS: After adjusting for potential confounders, PWV and cIMT were independently associated with ARV components in the total sample (P < 0.023 and P < 0.014, respectively). Within hypertensives only PWV and cIMT were independently associated with ARV components (P < 0.002 for PWV and P < 0.003 for cIMT). In contrast, within normotensives, only retinal parameters and AIx were associated with ARV components (P < 0.017 and P = 0.013, respectively). None of the univariate correlations between vascular parameters and wSD remained significant after adjustment for potential confounders. CONCLUSION: Short-term BPV as assessed by ARV is independently associated with macrovascular parameters in untreated hypertensive patients, and with microvascular parameters in normotensive individuals.

Assessment of microvesicles from different cell origins in patients with psoriasis: evidence of thrombogenic, proinflammatory microenvironment in the absence of established cardiovascular disease.

Psoriasis is associated with increased cardiovascular risk. Endothelial, platelet, and erythrocyte microvesicles (MVs) are novel biomarkers of endothelial dysfunction and thromboinflammation. We explored whether MVs of different cell types are elevated in patients with psoriasis, and investigated potential associations with disease severity and macrovascular function. Endothelial, platelet and erythrocyte MVs were measured using a standardized flow cytometry protocol in psoriasis patients and controls free from established cardiovascular disease. Carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were measured as markers of subclinical atherosclerosis and arterial stiffness. Psoriasis severity was assessed with PASI (Psoriasis Area Severity Index). Both platelet (p < 0.001) and erythrocyte MVs (p = 0.046), yet not endothelial MVs, were significantly increased in patients with psoriasis (n = 41) compared with controls (n = 41). Patients with higher PASI (≥10) presented significantly higher levels of ErMVs compared to those with lower PASI (<10) (p = 0.047). Carotid IMT and PWV were comparable between psoriasis patients and controls and did not significantly correlate with MVs. In the multivariate analysis, psoriasis was identified as an independent predictor of both platelet (p < 0.001) and erythrocyte MVs (p = 0.043), while hypertension was independently associated with endothelial MVs (p < 0.001). Increased formation of platelet and erythrocyte MVs may be evident in psoriasis patients and is indicative of prothrombotic, proinflammatory microenvironment, even in the absence of subclinical macrovascular dysfunction and before the clinical onset of overt cardiovascular complications. Potential mechanistic links and prognostic implications of increased MVs in psoriasis warrant further investigation.

Blunted Microvascular Reactivity in Psoriasis Patients in the Absence of Cardiovascular Disease, as Assessed by Laser Speckle Contrast Imaging.

Psoriasis is associated with accelerated rates of cardiovascular disease (CVD). Laser Speckle Contrast Imaging (LSCI) is a novel, non-interventional technique for the dynamic assessment of microvascular endothelial dysfunction, which represents an early precursor of CVD. We investigated whether skin microvascular reactivity is impaired in psoriasis and whether an association exists with large artery stiffening. Skin microvascular reactivity was assessed with LSCI combined with post-occlusive reactive hyperaemia protocol in psoriasis patients and controls in the absence of established CVD. Arterial stiffness and central hemodynamics were assessed throughout a whole 24 h period with the Mobil-O-Graph device. Most LSCI indices of microvascular reactivity were impaired in psoriasis patients (n = 90) compared to controls (n = 45) [baseline flux; occlusion flux; peak-to-baseline magnitude; baseline cutaneous vascular conductance (CVC); percentage increase in CVC, p < 0.001 for all comparisons]. In multivariate analysis, psoriatic disease predicted the above markers independently of classical CVD risk factors. Augmentation index, peripheral pulse pressure, and central systolic/diastolic blood pressure correlated with LSCI microvascular responses in the study population (n = 135). Pulse wave velocity significantly correlated with nearly all LSCI parameters, while the association with baseline flux was independent of CVD risk factors and psoriatic disease in multivariate analysis (beta = 0.096, p = 0.039). This study provides evidence of altered skin microvascular responses in psoriasis by use of LSCI, and interaction with macrovascular dysfunction, before the establishment of overt CVD. A non-interventional approach of skin microcirculation with LSCI might be used as an early indicator of vascular health in psoriasis.

Theories and Molecular Basis of Vascular Aging: A Review of the Literature from VascAgeNet Group on Pathophysiological Mechanisms of Vascular Aging.

Vascular aging, characterized by structural and functional alterations of the vascular wall, is a hallmark of aging and is tightly related to the development of cardiovascular mortality and age-associated vascular pathologies. Over the last years, extensive and ongoing research has highlighted several sophisticated molecular mechanisms that are involved in the pathophysiology of vascular aging. A more thorough understanding of these mechanisms could help to provide a new insight into the complex biology of this non-reversible vascular process and direct future interventions to improve longevity. In this review, we discuss the role of the most important molecular pathways involved in vascular ageing including oxidative stress, vascular inflammation, extracellular matrix metalloproteinases activity, epigenetic regulation, telomere shortening, senescence and autophagy.

Skin microvascular function, as assessed with laser speckle contrast imaging, is impaired in untreated essential and masked hypertension.

Skin microcirculation has been proposed as a model of generalized microvascular function. Laser speckle contrast imaging (LSCI) is a novel, noninvasive method to assess skin microvascular function (SMF). To date, SMF data in hypertension are conflicting, and no study with LSCI exists. In addition, the application of LSCI in masked hypertension is scarce. We assessed SMF with LSCI coupled with postocclusive reactive hyperemia (PORH) in patients with newly diagnosed untreated essential hypertension (UHT) and masked hypertension (MH) compared to healthy normotensive (NT) individuals. We enrolled consecutive UHT and MH patients and NT individuals matched for age, sex, body mass index, and smoking status. All participants underwent SMF assessment by LSCI coupled with PORH (PeriCam PSI system, Perimed, Sweden). Correlation analyses were performed between SMF and common cardiovascular risk factors and BP parameters. In total, 70 UHT patients, 20 MH patients and 40 NT individuals were enrolled. UHT and MH patients exhibited significantly impaired SMF compared to NT individuals (UHT patients: base-to-peak flux (p < 0.001)), PORH amplitude (p < 0.001); MH patients: base-to-peak flux (p = 0.013), PORH amplitude (p = 0.022). MH patients did not differ compared to UHT patients. SMF was negatively associated with office, ambulatory and central BP. SMF was negatively associated with blood lipids and smoking. Hypertensive status was the single most important predictor of SMF. UHT and MH patients exhibit impaired SMF compared to NT individuals. MH patients did not differ compared to UHT patients. SMF is negatively associated with BP and cardiovascular risk factors. LSCI could be implemented as a useful tool to investigate SMF in hypertension.

Assessment of skin microcirculation in primary aldosteronism: impaired microvascular responses compared to essential hypertensives and normotensives.

Primary aldosteronism (PA) is associated with considerably higher cardiovascular risk and increased prevalence of organ damage compared to essential hypertension (EH). Laser speckle contrast imaging (LSCI) has emerged as a novel non-invasive tool to assess of skin microcirculation. Our aim was to evaluate skin microvascular function (SMF) using LSCI coupled with post-occlusive reactive hyperemia (PORH) in a group of PA patients (PAs) compared to patients with EH (EHs) and normotensive controls (NTs). We enrolled PAs, age- and gender-matched with EHs and NTs. All participants underwent SMF assessment by LSCI with PORH. We enrolled 109 participants including 29 PAs, 47 EHs, and 33 NTs. SMF was significantly impaired in PAs, including peak time (p < 0.001) and base to peak flux (p < 0.001) compared to NTs and EHs. Among PAs, plasma aldosterone showed a positive correlation with occlusion flux (p = 0.005). Our study shows for the first time that PAs present impaired SMF as assessed with LSCI coupled with PORH, not only compared to NTs but also compared to EHs with similar blood pressure profile. Further studies are needed to investigate the clinical impact of such alterations in terms of pathophysiology and cardiovascular risk prediction.

A study of endothelial and platelet microvesicles across different hypertension phenotypes.

Rather than being mere biomarkers reflecting generalized vascular injury, endothelial- (EMVs) and platelet-derived (PMVs) microvesicles have emerged as potent regulators of intercellular communication with significant biologic effects in vascular homeostasis and several pathophysiological responses including inflammation and thrombosis. So far, studies in hypertension are scarce, whereas no studies exist in masked hypertension (MH). We measured EMVs and PMVs in untreated, newly diagnosed hypertensives (HTs) and MHs compared to normotensive controls (NTs), and associated them with various cardiovascular risk factors. Sustained hypertension (SHT) and MH were defined according to standard blood pressure (BP) criteria. All HTs were free of cardiovascular disease and medications. Microvesicles' quantitation and detection were performed by flow cytometry by using cell-specific antibodies and corresponding isotypes (anti-CD105 and anti-CD144 for EMVs, anti-CD42a for PMVs, and Annexin V-fluorescein isothiocyanate for all microvesicles). In this study, we included 59 HTs (44 SHTs and 15 MHs) and 27 NTs. HTs had significantly elevated EMVs (p = 0.004), but not PMVs compared to NTs. MHs had significantly elevated EMVs compared to NTs (p = 0.012) but not compared to SHTs. Furthermore, EMVs significantly correlated with ambulatory (r = 0.214-0.284), central BP (r = 0.247-0.262), and total vascular resistance (r = 0.327-0.361). EMVs are increased not only in SHTs but also in MHs, a hypertension phenotype with a cardiovascular risk close to SHT. EMVs have emerged as active contributors to thromboinflammation and vascular damage and may explain, in part, the adverse cardiovascular profile of SHTs and MHs.