196,370 research outputs found
Vascular calcification in diabetes mellitus: Molecular mechanisms and clinical implications
No full textCardiovascular risk assessment and diagnostic work-up in rare diseases: focus on hyperaldosteronism and primary antibody deficiency
No full textIntroduction: Unilateral form of primary aldosteronism (PA) is the main curable cause of endocrine hypertension cause of PA and it is in up to 66% of all cases investigated with adrenal vein sampling (AVS). Mutations in the KCNJ5 potassium channel involve up to 70% of unilateral PA. The in vitro evidences of macrolide antibiotics specifically inhibit the altered function of mutated KCNJ5 channels has opened new horizons for the diagnosis and treatment of unilateral PA with KCNJ5 mutations in that it can allow identification and target treatment of PA patients harbouring a mutated unilateral PA.
Aim: To test the effect of roxithromycin on aldosterone secretion and blood pressure in vivo in patients without PA, and in those with PA subtyped by AVS and examined according to the presence or absence of KCNJ5 mutation.
Methods: We enrolled consecutive hypertensive patients undergoing screening for secondary hypertension, from January 2018 to June 2022. Each patient received a single oral dose of roxithromycin and, after the diagnostic work-up, baseline values of plasma aldosterone concentration (PAC) and blood pressure were compared with post-roxithromycin values. Next- generation sequencing (NGS) was used to identify KCNJ5 mutated from wild-type forms of unilateral PA. Response to roxithromycin was compared between non-PA, non-unilateral PA and unilateral PA. In unilateral PA we focused on KCNJ5 mutated vs wild-type patients.
Results: After roxithromycin administration, patients with unilateral PA carring KCNJ5 mutation showed a decrease in PAC (p=0.030) that did not occur in unilateral PA KCNJ5 wild-type. In these groups systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not change in response to roxithromycin. However, in non-PA group a decrease in PAC was observed (p<0.001) with a decrease in plasma cortisol concentration (PCC) (p<0.001) and systolic (p<0.001) but not diastolic blood pressure. After adrenalectomy, roxithromycin did not induce any change in PAC in KCNJ5 mutated unilateral PA.
Conclusion: Roxithromycin administration induces a decrease in aldosterone production in patients with KCNJ5 mutation but not in wild-type, confirming its ability in vivo to blunt aldosterone production by blocking the mutated Kir3.4 sodium channel without affecting wild-type forms. As the decrease in PAC in the same patients did not occur after adrenalectomy, the roxithromycin effect is unequivocally attributable to the KCNJ5 mutated unilateral PA.Introduction: Although the immune system is involved in vascular disorders, the actual role of B cells in atherosclerotic cardiovascular disease (ASCVD) remains unclear. Inflammatory conditions like Rheumatoid Arthritis and Systemic Lupus Erythematosus present an accelerated atherosclerotic process, that is somehow limited by appropriate treatment, including B cell depleting therapies. Common Variable Immunodeficiency (CVID) is a rare primary immunodeficiency of adulthood and represents a pathological condition suitable for studying the role of B cells in ASCVD. The cardiovascular risk profile of patients affected by this rare disease is unexplored and it is unclear whether CVID patients are protected towards atherogenesis.
Aim: We investigated the prevalence of cardiovascular risk factors and the presence of subclinical ASCVD in CVID patients.
Methods: We collected anamnestic clinical and biochemical data related to CVID and to ASCVD in a single center cohort of CVID patients, grouped according to clinical and immunological phenotype. At follow-up visit vascular structural and functional investigation was performed by SphygmoCor(R) XCEL instrument while droplet digital PCR analysis was used to assess gene expression.
Results: 127 CVID patients were enrolled in the study. Patients with complicated phenotype presented significantly lower levels of cholesterol and blood glucose, despite a significantly higher use of corticosteroids (p=0.014) due to higher frequency of GLILD (p<0.001) and autoimmunity(p=0.007), particularly ITP (p<0.001). Patients with Chapel phenotype 2 and 3 presented the lowest cholesterol and HbA1c levels. No significant difference was found in terms of metabolic syndrome, hypertension, diabetes, anti-hypertensive, anti diabetic and lipid lowering ongoing treatment, as well as acute cardiovascular events between complicated and uncomplicated phenotype. Lower IgA, IgM IgG levels at diagnosis, SmB cells % as well as higher T-LGL % (CD3+CD8+CD57+) and monthly dosage of IgRT in the complicated group were the main between groups significantly different immunologic parameters. In vivo measurement by SphygmoCor(R) XCEL instrument in a subgroup of 55 patients showed significant difference pulse pressure and augmentation pressure, with a tendence towards higher arterial thickness in patients with only infections. In the same subgroup, B lymphocytes isolated from pheripheral blood of patients with complicated phenotype presented a borderline-significantly higher expression of LDL receptor gene at droplet digital PCR analysis (p=0.053). Conclusion: Our data suggest that clinical phenotypes of CVID may be associated with different cardiovascular risk profiles, possibly based on the different underlying immunological alterations. Preliminary data suggests that B cell defects in CVID patients might influence the development of cardiovascular disease leading to different cardiovascular risk profile. The role of IgRT also needs to be explored. Follow-up studies will unravel the significance of our subclinical findings in terms of development of overt disease, with possible implications in terms of new therapeutic strategies for ASCVD
Effect of regular physical activity on carotid intima-media thickness. Results from a 6-year prospective study in the early stage of hypertension
No full textAim. To study the effect of leisure-time physical activity on the progression of carotid intima-media thickness (IMT) in the early stage of hypertension. Methods. We studied 47 sedentary and 40 physically active young pre-hypertensive or stage 1 hypertensive subjects. IMT was assessed in the common carotid artery, carotid bulb and internal carotid artery at baseline and after 6.5 years. Results. Cumulative maximum IMT of the three carotid segments (M-MAX, 0.13 +/- 0.08 vs 0.10 +/- 0.07 mm, p = 0.006) and cumulative mean IMT (m-IMT, 0.11 +/- 0.07 vs 0.09 +/- 0.06 mm, p = 0.01), adjusted for con-founders, increased to a greater degree in the sedentary than the active subjects. Differences in known risk factors explained a large proportion of the observed association. Inclusion of baseline cholesterol in the regression model attenuated the strength of the association for both M-MAX (p - 0.04) and m-IMT (p - 0.049). When also baseline blood pressure, heart rate, and body mass index were taken into account the association with physical activity status remained significant for maximum IMT of internal carotid artery (p = 0.034) and was of borderline significance for M-MAX (p = 0.066). Conclusions. Physical activity can delay the progression of carotid IMT in hypertension. This effect is mediated in substantial part by the better risk factor profile in active subjects
Effect of regular physical activity on carotid intima-media thickness. Results from a 6-year prospective study in the early stage of hypertension.
No full textAIM: To study the effect of leisure-time physical activity on the progression of carotid intima-media thickness (IMT) in the early stage of hypertension.
METHODS: We studied 47 sedentary and 40 physically active young pre-hypertensive or stage 1 hypertensive subjects. IMT was assessed in the common carotid artery, carotid bulb and internal carotid artery at baseline and after 6.5 years.
RESULTS: Cumulative maximum IMT of the three carotid segments (M-MAX, 0.13 ± 0.08 vs 0.10 ± 0.07 mm, p = 0.006) and cumulative mean IMT (m-IMT, 0.11 ± 0.07 vs 0.09 ± 0.06 mm, p = 0.01), adjusted for confounders, increased to a greater degree in the sedentary than the active subjects. Differences in known risk factors explained a large proportion of the observed association. Inclusion of baseline cholesterol in the regression model attenuated the strength of the association for both M-MAX (p = 0.04) and m-IMT (p = 0.049). When also baseline blood pressure, heart rate, and body mass index were taken into account the association with physical activity status remained significant for maximum IMT of internal carotid artery (p = 0.034) and was of borderline significance for M-MAX (p = 0.066).
CONCLUSIONS: Physical activity can delay the progression of carotid IMT in hypertension. This effect is mediated in substantial part by the better risk factor profile in active subjects
Blood Pressure Variability and Therapeutic Implications in Hypertension and Cardiovascular Diseases
No full textBlood pressure (BP) is characterized by continuous dynamic and spontaneous oscillations occurring over lifetime and defining the so-called blood pressure variability (BPV). BPV has been associated with target organ damage, cardiovascular (CV) risk and death, suggesting the use of BPV as a new target in hypertension management in addition to mean BP values lowering. The purpose of the review is to focus on the therapeutic implications of BPV and summarize the effects of different drug classes on various types of BPV. Despite most first-line antihypertensive medications contribute to reduce both short and long term BPV, calcium channel blockers (CCBs) as monotherapy or fixed-combination therapy appear to be the most effective on BPV control. Further randomized interventional trials are needed to investigate which drug combinations are most appropriate according to patient CV risk stratification, in order to improve their CV outcomes
Best operative strategy for energy management of a cruise ship employing different distributed generation technologies
No full textThis paper aims to study the application of distributed generation technologies on a naval energy system, investigating the best operating strategy for energy management throughout an annual load profile. The thermo-economic analysis is performed considering electrical and thermal load demands referred to hotel and service loads of a cruise ship (around 6 MWel), both variable with the season and the period of the day, taking into account the off-design curves and cost functions for the different generators. Four different solutions are investigated, comparing the operative strategies in terms of energy efficiency, CO2 emissions and annual costs. The analysis is performed with dedicated software for the thermo-economic time-dependent analysis, developed by the University of Genoa. The thermo-economic approach has general validity, thus it can be also applied to different kinds of ships, even considering different technologies for energy generation and storage
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