Giovanni Trapani

Valutazione eco-Doppler dell'insufficienza venosa cronica di recente insorgenza in soggetti anziani: il cuore potrebbe avere un ruolo?

Riassunto. L’insorgenza in eta avanzata dei segni clinici di insufficienza venosa cronica (IVC), senza precedente storia di patologia venosa degli arti inferiori, pone degli interro gativi sulla causa eziologica. Nel nostro studio abbiamo va lutato le possibili cause indagando il sistema venoso degli arti inferiori e la funzione cardiaca destra in soggetti anzia ni con segni di IVC. Le alterazioni rilevate hanno riguardato la riduzione del TAPSE, un indice di massa corporea significativamente piu alto e una ridotta capacita deambulatoria rispetto al gruppo di controllo. Le differenze potrebbero es sere alla base dell’edema e delle alterazioni cutanee di re cente insorgenza. Se si tratta di IVC di tipo funzionale o di scompenso cardiaco congestizio in fase preclinica sara chia rito solo da adeguati follow-up. Parole chiave. Insufficienza venosa, scompenso destro, TAPSE. Echo-Doppler evaluation of recent onset chronic venous in sufficiency in elderly patients: does the heart have a role? Summary. The onset in elderly subjects of clinical signs of chronic venous insufficiency (CVI), without a previous history of venous disease of the lower limbs, raises questions about the etiology. In our study we evaluated the possible causes investigating the venous system of the lower limbs and right heart function in elderly subjects with signs of CVI. The alter ations found were on the reduction of TAPSE, a significantly higher body mass index and a reduced ability to walk com pared to the control group. The differences described could explain edema and skin changes of recent onset. If it is CVI functional type or of congestive heart failure in the preclinical stage will be clarified only by adequate follow-up.

Association between HMGB1 and COPD: A Systematic Review

HMGB1 is an alarmin, a protein that warns and activates inflammation. Chronic obstructive pulmonary disease (COPD) is characterised by a progressive airflow obstruction and airway inflammation. Current anti-inflammatory therapies are poorly effective in maintaining lung function and symptoms of COPD. This underlines the need for finding new molecular targets involved in disease pathogenesis in order to block pathology progression. This review aims to analyse latest advances on HMGB1 role, utilisation, and potential application in COPD. To this purpose we reviewed experimental studies that investigated this alarmin as marker as well as a potential treatment in chronic obstructive pulmonary disease. This systematic review was conducted according to PRISMA guidelines. In almost all the studies, it emerged that HMGB1 levels are augmented in smokers and in patients affected by COPD. It emerged that cigarette smoking, the most well-known causative factor of COPD, induces neutrophils death and necrosis. The necrosis of neutrophil cells leads to HMGB1 release, which recruits other neutrophils in a self-maintaining process. According to the results reported in the paper both inhibiting HMGB1 and its receptor (RAGE) and blocking neutrophils necrosis (inducted by cigarette smoking) could be the aim for further studies.

Clinical impact of angiotensin I converting enzyme polymorphisms in subjects with resistant hypertension

Angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism is thought to affect renin–angiotensin system (RAS) activity and development of cardiovascular disease; significant associations between I/D polymorphism and atherosclerosis, stroke, nephropathy, and early mortality were already found. We investigated whether Southern Italy resistant hypertensives presented an association between the presence of I and/or D alleles and early vascular damage, inflammation, and insulin resistance. One-hundred-fifty resistant hypertensives were enrolled, studied, and genotyped; carotid intima-media thickness (cIMT), arterial stiffness (AS), and HOMA indices were also evaluated. D allele was more prevalent, and 74 patients presented DD homozygosis. Sixty-eight patients had metabolic syndrome (MetS), without significant differences between DD and I allele carriers. DD genotype appeared strongly associated with higher HOMA values (p < 0.001), and also with both Augmentation Index (AIx, p = 0.003) and Pulse Wave Velocity (PWV, p = 0.023). A significant association was found between DD genotype and cIMT (p < 0.005), while no association between ACE genotype and the presence of carotid plaques. HOMA was correlated with AS (PWV: p < 0.001; AIx: p < 0.01). DD genotype appeared to be associated with AS and HOMA index, but not with inflammation, independently from blood pressure values and the presence of other MetS factors, confirming D allele as an independent risk marker. Vascular damage may develop and progress independently from other risk factors in resistant hypertensives, likely through the interplay between ACE gene, RAS activity, and insulin resistance.

Interleukin 31 and skin diseases: A systematic review.

BACKGROUND Although the pathophysiology of pruritus has been extensively studied in recent years, with many resultant advancements, management of pruritus is still enigmatic, particularly in chronic cutaneous diseases, such as atopic dermatitis, chronic urticaria, allergic contact dermatitis, cutaneous T-cell lymphoma, and uremic pruritus. The recent finding of the involvement of interleukin (IL) 31 in the pathogenesis of chronic pruritus has provided a novel approach to the management of chronic inflammatory skin disorders. The present report provided an in-depth overview of the role of IL-31 in chronic skin diseases and the possible diagnostic and therapeutic applications in the management of these diseases. METHODS A systematic review of IL-31 was conducted by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS A review of a total of 45 published research articles revealed that the majority of these articles focused on the role of IL-31 in causation of pruritus and in the worsening of the disease in atopic dermatitis. Other publications examined interleukin in other pruritic diseases (cutaneous T-cell lymphoma, uremic pruritus, allergic contact dermatitis, chronic urticaria). In almost every disease, IL-31 levels were reported to be correlated with the pathology and often with pruritus. The cutaneous injection of IL-31 resulted in a long-lasting itching sensation, and the use of monoclonal antibodies that targeted IL-31 led to a reduction in pruritus. CONCLUSION The use of monoclonal antibodies against mediators involved in the pathogenesis of chronic skin diseases has shown promising results. Antibodies that target IL-31, in particular, its receptor A, showed interesting results in atopic dermatitis and decreased pruritus. In subsequent years, the use of these new therapeutic strategies could change the scenario of pruritic skin diseases. However, further studies are needed to more rigorously examine the effects of IL-31 cascade blockage in different chronic skin diseases and to confirm efficacy and the safety of these new therapeutic approaches.

Combination therapy with aliskiren versus ramipril or losartan added to conventional therapy in patients with type 2 diabetes mellitus, uncontrolled hypertension and microalbuminuria.

Hypothesis/Introduction: The aim of this study was to assess the antihypertensive efficacy and safety of aliskiren versus ramipril or losartan in hypertensive patients with type 2 diabetes mellitus, microalbuminuria and uncontrolled hypertension, despite the use of optimal conventional antihypertensive therapy. Materials and methods: In this open-label active comparator study, 126 patients were randomly assigned to receive 24 weeks of additional therapy with aliskiren (Group A) or either losartan or ramipril (Group B), according to whether a patient was already treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, respectively. Results: After 24 weeks, both treatment groups experienced a significant reduction of systolic blood pressure (−11.37% and −8.47%, respectively; both p <0.001 vs. baseline) and diastolic blood pressure levels (−10.67% and −9.28%, respectively; both p <0.001 vs. baseline), with a greater reduction of mean systolic values in Group A compared with Group B (p <0.001). Furthermore, after six months microalbuminuria was significantly decreased in both treatment groups (−67.62% and −49.1%, respectively; both p <0.001), with a reduction rate in Group A significantly higher than in Group B (p<0.001). Conclusions: The addition of aliskiren to optimal conventional therapy provided a higher reduction of blood pressure and urinary albumin excretion when compared with the addition of losartan or ramipril.

Effect of type D personality on smoking status and their combined impact on outcome after acute myocardial infarction

Smoking cessation is correlated with several psychological, social, biological, and pharmacological aspects. The combined tendency to experience negative emotions and to inhibit the expression of these emotions is indicated as “type D personality,” an independent risk marker for clinical outcome in cardiac disease. Despite this effect of type D personality on cardiovascular disease, it is still unclear whether this personality trait may influence smoking cessation after a myocardial infarction.

Arterial stiffness and mitral regurgitation in arterial hypertension: An intriguing pathophysiological link

BACKGROUND We examined the relative impact of arterial stiffness on the presence and/or severity of chronic mitral regurgitation (MR) in hypertensive patients. METHODS We prospectively enrolled 141 untreated hypertensive patients (mean age 56.6 ± 11.5 years): 94 with MR, 47 without MR. As a measure of arterial stiffness, pulse wave velocity (PWV) was assessed by applanation tonometry. Assessment of MR severity was obtained through calculation of effective regurgitant orifice area (EROA) and vena contracta by standard two-dimensional transthoracic echocardiography. RESULTS PWV appears to progressively increase according to the presence and severity of MR (no MR = 7.3 ± 1.1 m/s, mild MR = 7.9 ± 1.3 m/s, moderate MR = 9.0 ± 1.7 m/s, severe MR = 13.3 ± 4.1 m/s; P < 0.001 for all comparisons). EROA was positively correlated with age (P = 0.011), left atrial volume index (P = 0.023), PWV (P < 0.001) and augmentation index (P < 0.001), and negatively correlated with left ventricular ejection fraction (P = 0.002) and heart rate (HR) (P = 0.018). On stepwise multivariate logistic regression analysis, only PWV (OR = 2.87, 95% CI 1.750-4.738, P < 0.001) and HR (OR = 0.94, 95% CI 0.895-0.994, P = 0.02) appeared to be independent predictors of severe MR. Receiver operating characteristic curves showed that a cutoff of 9 m/s for PWV provided the best sensitivity/specificity for predicting both the presence of any degree of MR (sensitivity 73%, specificity 87%, AUC = 0.863; P < 0.001) and MR severity (sensitivity 100%, specificity 81%, AUC = 0.954; P < 0.001). CONCLUSION Reduced arterial elasticity because of increased stiffness may be an important marker for the presence and severity of MR in hypertensive patients.

[OP.8A.09] EFFICACY OF MONOCLONAL ANTIBODIES ANTI-PROPROTEIN CONVERTASE SUBTILISIN-KEXIN TYPE 9 IN IMPROVING LIPID PROFILE AND ARTERIAL STIFFNESS IN PATIENTS AFFECTED BY FAMILIAL HYPERCHOLESTEROLEMIA

Objective: monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9), have emerged as a new class of drugs that effectively lower LDL cholesterol levels. Hypercholesterolemic patients present early signs of vascular inflammation and damage. We investigate whether after six months of treatment with anti-PCSK9 monoclonal antibodies we can find any improvement of pro-atherogenic profile and of arterial stiffness (AS) in patients affected by familial hypercholesterolemia already in treatment with the maximally tolerated statin therapy. Design and method: We enrolled 34 people who had decided to start treatment with anti-PCSK9 drugs; of these, 32 have completed the 6-months observation period. At enrollment and 6 months later we evaluated anthropometrics, laboratory profile, pulse wave velocity (PWV) and carotid intima-media thickness (cIMT). Results: After 6-months of treatment we found a significant decrease of inflammatory markers (Hs-CRP: −46.5%; Fibrinogen: −18.9%), LDL-C and lipoprotein (a) levels (respectively −65.9% and −34.2%). PWV (−9.5%) appeared to be improved; cIMT remained unchanged. PWV reduction appeared to be correlated with fibrinogen and LDL-C reduction. However, reduced PWV appeared to be not dependent on LDL-C and fibrinogen by the multiple regression analysis. Conclusions: After 6 months of treatment with monoclonal antibodies anti-PCSK9 the levels of CRP, Fibrinogen, LDL-C, and Lp (a), as well AS indices, are significantly improved as compared to baseline. We report the important evidence that a treatment with anti-PCSK9 monoclonal antibodies may improve significantly the arterial stiffness in patients affected by familial hypercholesterolemia.

[PP.10.19] RENAL DENERVATION RAPIDLY RESTORES CIRCULATING PROGENITOR CELLS IN PATIENTS AFFECTED BY RESISTANT HYPERTENSION

Objective: To investigate whether blood pressure (BP) lowering after renal sympathetic denervation (RSD) affects CD34+ cell number in drug-resistant hypertension (R-HTN). Design and method: We enrolled 11 patients with R-HTN, already treated with at least 6 antihypertensive drugs, including a diuretic, at full dosages; patients with office BP of >160 mmHg (>150 mmHg for type 2 diabetes) were considered eligible for the procedure. Adherence to drug treatment was accurately checked by patients general practitioners. Mean age was 61 ± 7.9 years; M:F 8:5. We measured clinic (sphygmomanometer) and ambulatory (Tonoport V GE-Healthcare) BP, and heart rate (HR; electrocardiogram), at baseline and 30 days after RSD procedure (Symplicity; Medtronic). 24 h BP recordings and home BP protocols were consulted in addition to office BP measurements at the hospital before enrollment. Results: At T0: SBP: 179.1 ± 9.3mmHg; DBP: 101.2 ± 5.5 mmHg; HR 79.9 ± 9.4; CD34+ cells: 1.66 ± 0.51. At T1 SBP values were reduced on the average of 40.2 mmHg (138.9 ± 7.3; −22.5%, p < 0.001) DBP of 18 mmHg (83.2 ± 3.2; −17.7%, p < 0.001), and HR of 10.4 bpm (67.3 ± 6.0; −17.7%, p < 0.005), and CD34+cell number increased on an average of 0.34 cells /microL (2.0 ± 0.51; +21.2%, p < 0.001). Conclusions: RSD rapidly restores CD34+cell number in patients affected by true R-HTN; if these results will be confirmed on a larger scale, they could provide new insights about CD34+ cells and pathophysiological aspects of arterial hypertension.

[PP.23.10] CLINICAL IMPACT OF ANGIOTENSIN CONVERTING ENZYME (ACE) POLYMORPHISM ON DEVELOPMENT OF CARDIOVASCULAR AND METABOLIC COMPLICATIONS IN SUBJECTS WITH RESISTANT HYPERTENSION

Objective: The renin-angiotensin system and endothelial function have been both associated with hypertension, but there are very few data in resistant hypertension. The aim of the present study was to assess the relationship between insertion/deletion polymorphism in the gene encoding the angiotensin-converting enzyme (ACE I/D) and estimation of cardiovascular and metabolic complications in resistant hypertensive patients. Design and method: In the present study we analyzed and genotyped data from 150 patients with resistant hypertension. We have evaluated arterial stiffness (AS) indices, carotid intima-media thickness (cIMT), HOMA index and clinical data. Results: D allele was more prevalent, and 74 patients presented DD homozygosis. Sixty-eight patients had metabolic syndrome (MetS), without significant differences between DD and I allele carriers. DD genotype appeared strongly associated with higher HOMA values (p < 0.001), and also with both AIx (p = 0.003) and PWV (p = 0.023). A significant association was found between DD genotype and cIMT (p < 0.005), and the presence of carotid plaques (p < 0.001). HOMA was correlated with AS (PWV: p < 0.001; AIx: p < 0.01). Conclusions: Our results are in agreement with experimental evidences suggesting that DD genotype appeared to be associated with AS, increased cIMT, HOMA index, and the presence of carotid plaques, and confirming that D allele plays an important risk role on development of cardiovascular and metabolic complications in patients with resistant hypertension, independently from the presence of other risk factors.