Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of the cases of HF worldwide. Among the different phenotypes, cardiometabolic HFpEF has the highest prevalence. Cumulative insults related to cardiometabolic comorbidities-obesity, hypertension and type 2 diabetes-create a milieu of metabolic derangements, low-grade systemic inflammation (i.e., metainflammation), endothelial dysfunction, and coronary microvascular disease. Emerging data indicate that the gut-heart axis is a potential amplifier of this process. Cardiometabolic comorbidities promote gut dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, and disruption of the intestinal barrier, leading to endotoxemia and upregulation of pro-inflammatory pathways such as TLR4- and NLRP3-mediated signaling. Concomitantly, beneficial gut-derived metabolites (acetate, propionate, butyrate) decrease, while detrimental metabolites increase (e.g., TMAO), potentially fostering myocardial fibrosis, diastolic dysfunction, and adverse remodeling. SCFAs-acetate, propionate, and butyrate-may exert pleiotropic actions that directly target HFpEF pathophysiology: they may provide a CPT1-independent energy substrate to the failing myocardium, may improve lipid and glucose homeostasis via G protein-coupled receptors and AMPK activation, and may contribute to lower blood pressure and sympathetic tone, reinforce gut barrier integrity, and act as anti-inflammatory and epigenetic modulators through the inhibition of NF-κB, NLRP3, and histone deacetylases. This review summarizes current evidence linking gut microbiota dysfunction to cardiometabolic HFpEF, elucidates the mechanistic role of SCFAs, and discusses nutritional approaches aimed at enhancing their production and activity. Targeting gut-heart axis and SCFAs pathways may represent a biologically plausible and low-risk approach that could help attenuate inflammation and metabolic dysfunctions in patients with cardiometabolic HFpEF, offering novel potential therapeutic targets for their management.

Subclinical carotid artery disease anticipates major cardiovascular events, and previous studies show that low vitamin D levels are associated with arterial stiffening in hypertension. The aim of the study was to examine the relationship of 25-hydroxyvitamin D [25(OH)D] levels with subclinical carotid disease in hypertensive patients. In 223 middle-aged, nondiabetic, primary hypertensive patients free of major cardiovascular and renal complications, we measured 25(OH)D and parathyroid hormone (PTH) and assessed subclinical carotid arteries changes by B-mode ultrasonography. The carotid intima-media thickness (IMT) and presence of plaques were assessed together with measurements of indexes of carotid artery distensibility (coefficient of distensibility) or stiffening (Young’s elastic modulus; β-stiffness). Lower 25(OH)D levels were associated with older age (p < 0.001), longer duration of hypertension (p = 0.019), higher fasting plasma glucose (p = 0.037), and insulin (p = 0.044), Homeostatic Model Assessment (HOMA) index (p = 0.044), and PTH (p < 0.001). Insufficient and deficient 25(OH)D were associated with progressively greater carotid IMT (p < 0.001), frequency of carotid plaques (p = 0.026), Young’s elastic modulus (p = 0.002), and β-stiffness (p < 0.001), and progressively lower carotid coefficient of distensibility (p < 0.001). Serum levels of 25(OH)D were negatively correlated with age (p < 0.001), duration of hypertension (p = 0.006), fasting glucose (p < 0.001), HOMA index (p = 0.032), PTH (p < 0.001), carotid IMT (p < 0.001), Young’s elastic modulus (p = 0.025), and β-stiffness (p < 0.001), and positively related with carotid coefficient of distensibility (p < 0.001). Multivariate regression analysis showed that both higher carotid IMT (p = 0.004) and lower coefficient of distensibility (p = 0.002) were related to lower 25(OH)D independent of age, severity, and duration of hypertension and metabolic variables. In conclusion, deficiency/insufficiency of 25(OH)D independently predicts subclinical carotid disease in uncomplicated, middle-aged, hypertensive patients and might predispose these patients to major cardiovascular complications.

Background and aimsA prothrombotic state was demonstrated in patients with Cushing’s syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension.MethodsIn 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol).ResultsPlasma levels of D-dimer (D-dim), prothrombin fragment 1 + 2 (F1 + 2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1 + 2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1 + 2, and vWF independently of age, body mass index, blood pressure, and renal function.ConclusionGreater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

As of 2024, arterial hypertension is still considered the leading modifiable cardiovascular risk factor and, due to high rates of undertreatment and poor blood pressure control, the major contributor to human morbidity and mortality. Development of new treatment options and better interventions in lifestyle correction have become a priority of experimental and clinical research. In the last decades, dietary supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and generation of gut microbiota-derived short chain fatty acids (SCFAs) have surged as potential and promising interventions for hypertension and cardiovascular prevention. ω-3 PUFAs are considered "essential" fatty acids that can be obtained only from dietary sources. Although previous intervention trials were not consistent in reporting a significant benefit of ω-3 PUFAs, the recent REDUCE-IT trial has provided robust evidence in support of their role in cardiovascular prevention. Recent studies have also identified the intestinal microbiota as a potential player in the pathophysiology and progression of hypertension. Although this might occur through many pathways, generation of SCFAs that is highly dependent on dietary fiber intake is primarily involved, providing an additional target for the development of novel therapeutic strategies. For these reasons, some scientific societies currently recommend dietary supplementation of ω-3 PUFAs and fiber-containing foods in patients with hypertension. In this narrative review, we summarize the results of studies that examined the effects of ω-3 PUFAs and SCFAs on blood pressure, highlighting the mechanisms of action on the vascular system and their possible impact on hypertension, hypertension-related organ damage and, ultimately, cardiovascular outcomes.

Objective: The study of cortisol secretion and the response of plasma aldosterone concentration (PAC) to saline infusion test (SIT) are used to exclude some forms of secondary arterial hypertension. Some studies show a relationship between agents stimulating cortisol and aldosterone production, but the mechanisms have not yet been clarified, moreover the effects of cortisol concentration on PAC after a SIT test have never been studied. Design and method: In 112 essential hypertensive (EH) patients (age 48±13 years, 63 males, free of interfering hypertensive treatment) we evaluated clinical characteristics, plasma and urinary sodium and potassium, plasma cortisol at 8AM, 5PM, 11PM, 24-h urinary free cortisol, cortisol values after an overnight suppression test with 1 mg of dexamethasone (DST), and active renin and PAC before and after a saline infusion test. Results: PAC after SIT was significantly and directly related to PAC before SIT (r=0.349, P<0.001), ACTH level (r=0,233, P=0,021) and inversely related to post-DST cortisol level (r=-0.225, P=0.018), while being weakly related to GFR (r=-0,179, P=0,060). We performed a multivariate analysis with post-SIT PAC as dependent variable, including PAC before SIT test, post-DST cortisol, ACTH levels and GFR as independent variables. In this analysis post-SIT PAC was independently associated with pre-SIT PAC (B=0.225, P=0,024) and post-DST cortisol (B=-0.213, P=0.027). Conclusions: Although the physiological relationship between glucocorticoid and mineralocorticoid synthesis is not yet fully understood, these results indicate that a mild overproduction of cortisol, even if subclinical, might influence the PAC response to SIT test. We believe that this fact should be considered by the physician during the diagnostic work-up of secondary and resistant hypertension.

Objective: Glycometabolic changes are associated with hypercortisolism in Cushing's syndrome. Because impaired glucose tolerance (IGT) and insulin resistance are frequently detected in patients with essential hypertension, we hypothesized that in these patients, early glycometabolic abnormalities might be related to differences in regulation of cortisol secretion. Methods: In a cross-sectional study, we included 155 nondiabetic, essential hypertensive patients who were free of organ complications. The homeostasis model assessment (HOMA) index and the area under the curve of plasma glucose (AUC-glucose) and insulin (AUC-insulin) concentration following an oral glucose tolerance test were measured, together with daily plasma cortisol (8 a.m., 3 p.m. and 12 a.m.; AUC-cortisol) and 8 a.m. cortisol after 1 mg overnight dexamethasone suppression test (DST). Results: IGT was present in 27% of patients who were older and had higher BMI, plasma triglycerides and uric acid, AUC-cortisol and DST-cortisol, and lower HDL-cholesterol. Frequency of IGT increased progressively across tertiles of DST-cortisol, together with levels of glycated hemoglobin, fasting insulin and C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. AUC-cortisol and DST-cortisol were directly correlated with insulin, C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. Multivariate regression analysis showed that DST-cortisol was directly and independently correlated with HOMA index, AUC-glucose, and AUC-insulin. In a logistic regression model, both AUC-cortisol and DST-cortisol independently predicted IGT. Conclusion: Daily cortisol and cortisol response to DST are independent determinants of IGT and insulin resistance in nondiabetic patients with hypertension, suggesting that even subtle differences in regulation of cortisol secretion might increase the risk of these patients to develop diabetes.

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce "residual cardiovascular risk" in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage.

Background and aims Past studies reported a significant contribution of a prothrombotic state to the development and progression of target organ damage in hypertensive patients. Stiffening of arterial vessels is associated with aging and hypertension, and additional factors could contribute to this process. This study was designed to examine the relationships between arterial stiffening and the hemostatic and fibrinolytic system. Methods In 128 middle-aged, nondiabetic, essential hypertensive patients without major cardiovascular and renal complications, we measured coagulation markers that express the spontaneous activation of the hemostatic and fibrinolytic system and assessed stiffness of the arterial tree by measurement of the carotid/femoral pulse wave velocity (cfPWV) and pulse wave analysis with calculation of the brachial augmentation index (AIx). Results Levels of fibrinogen (FBG), D-dimer (D-d), and plasminogen activator-inhibitor 1 (PAI-1) were significantly higher in patients with PWV and AIx above the median of the distribution. FBG, D-d, and PAI-1 were significantly and directly related with both cfPWV and AIx, and multivariate regression analysis indicated that the relationships of D-d and PAI-1 with both cfPWV and AIx and of FBG with AIx, were independent of age, body mass index, severity and duration of hypertension, use of antihypertensive drugs, blood glucose, and plasma lipids. Conclusion In middle-aged, uncomplicated, nondiabetic patients with essential hypertension, spontaneous activation of plasma hemostatic cascade and impaired fibrinolysis is significantly and independently associated with stiffening of the arterial tree.

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar–arterial oxygen difference (A-aDO2), oxygen saturation

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans’ health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality, the relationship of alcohol consumption with blood pressure (BP) has been the subject of extensive investigation. For the purpose of this review, we searched the terms “alcohol”, “ethanol”, and “arterial hypertension” on Pubmed MeSH and selected the most relevant studies. Short-term studies showed a biphasic BP response after ingestion of high doses of alcohol, and sustained alcohol consumption above 30 g/day, significantly, and dose-dependently, increased the risk for hypertension. These untoward effects of alcoholic beverages on BP can be mediated by a multiplicity of neurohormonal mechanisms. In addition to the effects on BP, excess alcohol intake might contribute to cardiac and renal hypertensive organ damage, although some studies suggest possible benefits of moderate alcohol consumption on additional cardiovascular risk factors, such as diabetes and lipoprotein(a). Some intervention studies and cumulative analyses support the evidence of a benefit of the reduction/withdrawal of alcohol consumption on BP and cardiovascular outcomes. This is why guidelines of scientific societies recommend avoidance or limitation of alcohol intake below one unit/day for women and two units/day for men. This narrative article overviews all these topics, providing an update of the current knowledge on the relationship between alcohol and BP.

Granulomatosis with polyangiitis (GPA) is an ANCA-associated small-vessel vasculitis. Vessel wall inflammation induces multiple vascular damages, leading to accelerated atherosclerosis. Metabolic profile and cardiovascular risk are somewhat understood in GPA patients. Cardiovascular atherosclerotic disease (ASCVD) may represent a risk for outcomes. Our purpose is to evaluate ASCVD risk in GPA patients. Thirty-six patients received GPA diagnosis (T0) and were evaluated after 1 (T1) and 2 (T2) years follow-up. All patients were treated with high-dose glucocorticoid, one-year tapered, along with immunosuppressants. Total cholesterol significantly increased in T1 vs. T0 and T2. LDL exhibited the same trend, while triglycerides increased in both T1 and T2 vs. T0. No difference was found in HDL. A significant hsCRP decrease was detected at T1 and T2 vs. T0, but not between T2 and T1. Moreover, we found a significant reduction in ESR at T2 compared with T1 and T0 and at T1 compared to T0. Hypertensive patients presented a pronounced increase in lipids, while inflammation reduced slowly compared to normotensives. Our data suggest that the increase in cholesterol and LDL in T1 is a consequence of glucocorticoids. These data can be useful in the evaluation of both CV diseases and lipid metabolism, which are closely related to vessel inflammation.

Objective: Nutritional interventions potentially preventing hypertension-related organ damage are far to be fully defined. Coffee is one of the most used beverages all over the world. Many studies tried to define the optimal amount of coffee in order to understand whether coffee has a role in cardiovascular prevention. Thus, we evaluated vascular stiffness in well controlled hypertensives according to coffee consumption. Design and method: We evaluated well-treated 449 patients (225F, 224M, aged 62.56±11.49) with essential hypertension. All patients were checked for organ damage screening including carotid-femoral pulse wave velocity (cfPWV), Augmentation Index (AI), and ankle-brachial Index (ABI). To evaluate microcirculation, amydriatic retinography was performed. Arteriolar-to-Venular diameter Ratio (AVR). The number of coffee cups per day was asked during the visit. The median coffee consumption was 2 cups per day. Results: Patients were subdivided into three groups according to tertiles of cups consumed: Group 1, 0-1 cups 148 patients (87F, 61M; 63.66±12.94), Group 2, 2 cups, 159 patients (77F; 82M; 64.75±10.09), Group 3, >2 cups, 142 patients (60F; 82M; 58.96±10.54). No differences highlighted in BMI, in SBP/DBP, in cfPWV and in ABI. On the contrary, aortic stiffness evaluated as AI results significantly decreased in high coffee consumers compared to other groups (ANOVA p<0.0001). In particular, Group 3 was lower than Group 1 (Group 3 9.54±15.48 vs Group 1 17.49 ± 19.56, p<0.05) and (Group 3 9.54±15.48 vs Group 2 15.88 ± 16.57, p<0.05). AVR was higher in less coffee consumers compared to higher (Group 1 0.91 ± 0.10 vs group 3 0.87 ± 0.11, p<0.05), but no difference resulted between Group 2 and 3 or Group 1 and 2. Moreover, AVR did not correlate to Augmentation Index in any group. Conclusions: Coffee consumption may have a role in prevention of aortic remodelling and stiffness. Consumption of at least 3 cups of coffee per day reduces vascular stiffness and increase central vascular compliance, despite this effect is reduced in distal vascular circulation. Our findings need further analysis, mainly to the effects in distal/central hemodynamics due to different drug treatment.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are “essential” fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of “residual” cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented “pleiotropic” actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids.

Objective: The non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular events. At the same time a subclinical carotid change is associated with mortality and morbidity in hypertension. However it's unclear if there is a relationship between NAFLD and subclinical carotid damage in essential hypertension (EH). We searched for relationships between biochemical non-invasive NAFLD scores and subclinical carotid damage in a group of naïve EH patients. Design and method: In 299 naïve EH subjects (age 50 ± 13 years, 132 males) we evaluated clinical characteristics, biochemical scores of liver steatosis, as liver Fat Score (LFS), and fibrosis, as NAFLD Fibrosis Score (NFS), APRI, Fibrometer, and FIB-4, presence of echographic steatosis, metabolic syndrome, diabetes, levels of glucose, insulin, HOMA, lipids, glomerular filtration rate (GFR), reactive C protein (RCP), liver tests, platelet count, smoking habit and physical activity. By ultrasound carotid examination we measured the intima-media thickness (IMT), presence of carotid plaques, and in 115 subjects we calculated the carotid stiffness indexes, as the distension coefficient, the beta-stiffness, and the Young elastic module. Results: The IMT significantly increased across quartiles of LFS (P = 0.036), NFS (P = 0.001) and FIB-4 (P = 0.003). IMT was independently associated with FIB-4 (B = 0.380, P = 0.003) and NFS (B = 0.221, P = 0.013) scores. A IMT > 0.9 mm was independently associated with FIB-4 (P = 0.042). Patients with plaques had higher APRI (P = 0.005), Fibrometer (0.023), NFS (P < 0.001) and FIB-4 (P = 0.005) scores, and prevalence of plaques increased progressively across quartiles of LFS (P = 0.046), NFS (P < 0.001) and FIB-4 (P = 0.005). There was an independent association between carotid distension coefficient and Fibrometer (B = -0.360, P = 0.029), and between beta-stiffness and Fibrometer (B = 0.340, P = 0.036). Conclusions: In naïve EH patients the carotid IMT and carotid stiffness are independently associated with non-invasive NAFLD indexes. This association could induce to a more careful evaluation of a non-alcoholic liver damage in EH patients with subclinical carotid alterations. Moreover, studies are needed to clarify if profibrotic mechanisms are the base of both damages.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

Background: Left ventricular (LV) abnormalities were reported in patients with overt and subclinical Cushing syndrome. The aim of this study was to investigate the relationships of daily plasma cortisol profile and cortisol response to an overnight suppression test with cardiac changes in patients with hypertension. Methods: In a cross-sectional study, we included 136 nondiabetic, patients with essential hypertension who were free of cardiovascular and renal complications. Plasma cortisol was measured at 8 am , 3 pm , and 12 am and at 8 am after overnight suppression with 1 mg dexamethasone (dexamethasone suppression test [DST]). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. Results: LV hypertrophy was present in 30% and LV diastolic dysfunction in 51% of patients who were older and had significantly higher body mass index, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol. LV mass index and relative wall thickness increased progressively across tertiles of DST cortisol, together with progressive worsening of diastolic function. LV mass index was directly related to age, systolic blood pressure, duration of hypertension, and 12 am and DST cortisol, and inversely to creatinine clearance. Multivariate regression analysis showed independent correlation of LV mass index with body mass index, systolic blood pressure, and 12 am and DST cortisol. Logistic regression showed that DST cortisol independently predicted LV hypertrophy. Conclusions: Midnight and DST plasma cortisol levels are independent determinants of LV mass and geometry in patients with essential hypertension suggesting that even minor changes in regulation of cortisol secretion could contribute to cardiac abnormalities in these patients.

In patients who recovered from COVID-19 pneumonia the aortic stiffness is associated with severity of disease and levels of proADM, but not with history of hypertension. Patients with more higher proADM levels in acute phase of the infectious disease could need a longer follow-up evaluation of the CFPWV after the recovering from disease to search for long time vascular damage.

Recent evidence indicates that mildly increased fasting and post-oral load blood glucose concentrations contribute to development of organ damage in nondiabetic patients with hypertension. In previous studies, vitamin D deficiency was associated with decreased glucose tolerance. The aim of this study was to examine the relationships between serum 25(OH)D levels and glucose tolerance and insulin sensitivity in hypertension. In 187 nondiabetic essential hypertensive patients free of cardiovascular or renal complications, we measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and performed a standard oral glucose tolerance test (OGTT). Patients with 25(OH)D deficiency/insufficiency were older and had significantly higher blood pressure, fasting and post-OGTT (G-AUC) glucose levels, post-OGTT insulin (I-AUC), PTH levels, and prevalence of metabolic syndrome than patients with normal serum 25(OH)D. 25(OH)D levels were inversely correlated with age, blood pressure, fasting glucose, G-AUC, triglycerides, and serum calcium and PTH, while no significant relationships were found with body mass index (BMI), fasting insulin, I-AUC, HOMA index, and renal function. In a multivariate regression model, greater G-AUC was associated with lower 25(OH)D levels independently of BMI and seasonal vitamin D variations. Thus, in nondiabetic hypertensive patients, 25(OH)D deficiency/insufficiency could contribute to impaired glucose tolerance without directly affecting insulin sensitivity.