Non-Invasive Assessment of Micro- and Macrovascular Function after Initiation of JAK Inhibitors in Patients with Rheumatoid Arthritis.

BACKGROUND: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. METHODS: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima-media thickness was assessed with ultrasound. RESULTS: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. CONCLUSIONS: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA.

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.

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.

Contribution of single office aortic systolic blood pressure measurements to the detection of masked hypertension: data from two separate cohorts.

Masked hypertension (MH) and masked uncontrolled hypertension (MUH) remain largely underdiagnosed with no efficient detection algorithm. We recently proposed a novel classification of office systolic hypertension phenotypes defined on the basis of both brachial and aortic systolic blood pressure (bSBP/aSBP) and showed that type III ("isolated high office aSBP" phenotype: normal office bSBP but high office aSBP) has higher hypertension-mediated organ damage (HMOD). We tested whether MH/MUH (1) can be detected with the "isolated high office aSBP" phenotype and (2) if it is associated with elevated office aSBP with respect to normotension. We classified two separate and quite different cohorts (n = 391 and 956, respectively) on the basis of both bSBP and aSBP into four different phenotypes. Participants were classified as sustained hypertensives, masked hypertensives/masked uncontrolled hypertensives (MHs/MUHs), white coat hypertensives, and normotensives according to their office and out-of-office BP readings. The majority (more than 60% in cohort A and more than 50% in cohort B) of type III individuals were MHs/MUHs. Almost 35% of MHs/MUHs had optimal office bSBP rather than high normal bSBP. In both cohorts, the detection of more than 40% of MH/MUH was feasible with the type III phenotype. MHs/MUHs had higher office aSBP than individuals with sustained normotension (p < 0.05). In conclusion, in the absence of an efficient screening test, the diagnosis of MH/MUH can be assisted by the detection of the "isolated high office aSBP" phenotype, which can be measured in a single office visit. MHs/MUHs have increased aSBP relative to normotensives, further explaining the increased mortality of MH/MUH.

Assessment of Endothelial Injury and Pro-Coagulant Activity Using Circulating Microvesicles in Survivors of Allogeneic Hematopoietic Cell Transplantation.

(1) Background: survivors of allogeneic hematopoietic cell transplantation (alloHCT) suffer from morbidity and mortality due to cardiovascular events. We hypothesized that vascular injury and pro-coagulant activity are evident in alloHCT survivors without existing alloHCT complications or relapse. (2) Methods: we enrolled consecutive adult alloHCT survivors without established cardiovascular disease and control individuals matched for traditional cardiovascular risk factors (January-December 2019). Circulating microvesicles (MVs) of different cellular origins (platelet, erythrocyte, and endothelial) were measured by a standardized flow cytometry protocol as novel markers of vascular injury and pro-coagulant activity. (3) Results: we recruited 45 survivors after a median of 2.3 (range 1.1-13.2) years from alloHCT, and 45 controls. The majority of patients suffered from acute (44%) and/or chronic (66%) graft-versus-host disease (GVHD). Although the two groups were matched for traditional cardiovascular risk factors, alloHCT survivors showed significantly increased platelet and erythrocyte MVs compared to controls. Within alloHCT survivors, erythrocyte MVs were significantly increased in patients with a previous history of thrombotic microangiopathy. Interestingly, endothelial MVs were significantly increased only in alloHCT recipients of a myeloablative conditioning. Furthermore, MVs of different origins showed a positive association with each other. (4) Conclusions: endothelial dysfunction and increased thrombotic risk are evident in alloHCT recipients long after alloHCT, independently of traditional cardiovascular risk factors. An apparent synergism of these pathophysiological processes may be strongly involved in the subsequent establishment of cardiovascular disease.

Noninvasive Assessment of Myocardial Perfusion in Different Blood Pressure Phenotypes and Its Association With Arterial Stiffness Indices.

BACKGROUND: We investigated for the first time whether patients with recent-onset, uncomplicated hypertension and different hypertension phenotypes exhibit altered values of subendocardial viability ratio (SEVR), a surrogate measure of myocardial perfusion that correlates with the ratio of subendocardial to subepicardial blood flow. We additionally explored whether SEVR correlates with arterial stiffness in a population free from the long-term effects of essential hypertension. METHODS: Nontreated individuals free from any known health problems were classified as true hypertensives (THs), white-coat hypertensives (WCHs), masked hypertensives (MHs), and normotensives. SEVR was noninvasively calculated with applanation tonometry in the radial artery. Carotid-femoral pulse wave velocity, central and peripheral pulse pressure (PP), augmentation index, and central systolic/diastolic blood pressure (BP) were assessed with applanation tonometry. Total arterial compliance index was calculated with impedance cardiography. RESULTS: In a total of 150 participants, normotensive individuals exhibited the highest values of SEVR (162.9 ± 25.3%), whereas SEVR appeared to be similar in MHs (150.2 ± 22.1%), WCHs (148.1 ± 20.4%), and THs (149.9 ± 24.8%) (P = 0.017). In the univariate analysis, SEVR significantly correlated with central systolic BP, peripheral PP, and total arterial compliance index. The association between SEVR and both central (P = 0.017) and peripheral PP (P = 0.003) remained significant after adjustment for heart rate and other parameters. CONCLUSIONS: SEVR, an alternative tool to the invasive assessment of microvascular coronary perfusion, presents different values across patients with divergent BP phenotypes and correlated with arterial stiffness, even in the absence of overt cardiovascular disease. Future studies need to address the potential utility of this easily implementable marker as a screening test for myocardial ischemia.

Capillary rarefaction as an index for the microvascular assessment of hypertensive patients.

Arterial hypertension represents a leading cause of cardiovascular mortality and morbidity worldwide through its detrimental effects on target organs. Therefore, the early identification and appropriate management of high-risk patients emerges as extremely important. Given that the microvasculature is subject to a series of morphological and functional changes under the continuous effect of high blood pressure, research over the last years has gradually moved toward the identification of specific microcirculatory alterations that may serve as early prognostic markers of cardiovascular risk. Dermal capillaries represent an "open window" for the in vivo study of human microcirculation that has been long used mainly for the study of rheumatic diseases. However, capillaroscopy has been relatively understudied and only recently applied in the field of hypertension. Capillaroscopy represents a forthcoming promising estimate of the microvascular status in hypertensive patients, with capillary rarefaction representing the most typical finding. The present review aims at summarizing available evidence and the main findings, as well as the premises and promises, of capillary rarefaction as a tool for evaluating patients with hypertension.