N-palmitoyl-d-glucosamine limits mucosal damage and VEGF-mediated angiogenesis by PPARα-dependent suppression of pAkt/mTOR/HIF1α pathway and increase in PEA levels in AOM/DSS colorectal carcinoma in mice.

Chronic intestinal inflammation and neo-angiogenesis are interconnected in colorectal carcinoma (CRC) pathogenesis. Molecules reducing inflammation and angiogenesis hold promise for CRC prevention and treatment. N-Palmitoyl-d-glucosamine (PGA), a natural glycolipid analog with anti-inflammatory properties, has shown efficacy against acute colitis. Micronized PGA (mPGA) formulations exhibit superior anti-inflammatory activity. This study investigates the in vivo anti-angiogenic and protective effects of mPGA in a mouse model of colitis-associated CRC induced by azoxymethane/dextran sodium sulfate (AOM/DSS). CRC was induced in C57BL/6J mice using intraperitoneal azoxymethane followed by three cycles of 2.5% dextran sodium sulfate (DSS) in drinking water. Mice were treated with mPGA (30-150 mg/kg) with or without the PPARα inhibitor MK886 (10 mg/kg). At Day 70 post-azoxymethane injection, mice underwent anesthetized endoscopic colon evaluation. Post-mortem analysis of tumorigenesis and angiogenesis was performed using histological, immunohistochemical, and immunoblotting techniques. mPGA improved disease progression and survival rates in a dose- and PPARα-dependent manner in AOM/DSS-exposed mice. It reduced polyp formation, decreased pro-angiogenic CD31, pro-proliferative Ki67, and pro-inflammatory TLR4 expression levels, and inhibited VEGF and MMP-9 secretion by disrupting the pAkt/mTOR/HIF1α pathway. mPGA increased colon PEA levels, restoring anti-tumoral PPARα and wtp53 protein expression. Given its lack of toxicity, mPGA shows potential as a nutritional intervention to counteract inflammation-related angiogenesis in CRC.

Safety and Efficacy of Combined Coronary and Peripheral Percutaneous Revascularization: A Proof-of-Concept Study.

Background. Lower extremity peripheral artery disease (LEPAD) frequently coexists with coronary artery disease (CAD) in patients with multisite vascular disease (MVD). While percutaneous revascularization is well-established for both LEPAD and CAD, limited evidence exists for patients eligible for both procedures. Specifically, the feasibility of concomitant LEPAD and CAD percutaneous revascularization remains unknown. Objectives. To compare the efficacy and safety of concomitant coronary and lower extremity elective percutaneous revascularization. Methods. Between 2012 and 2021, we included 135 patients in an observational, retrospective single-center registry. The population was stratified into two groups: 45 patients (concomitant group) underwent simultaneous coronary and peripheral percutaneous interventions, and 90 patients (deferred group) underwent two separate procedures within one year. The primary efficacy endpoint was major adverse cardiovascular events (MACE) at one year, while the primary safety endpoint was in-hospital contrast-induced nephropathy (CIN). Results. Study groups were well-balanced in baseline characteristics. In terms of coronary features, the concomitant revascularization group more often underwent single-vessel percutaneous coronary intervention (PCI), while the deferred group had multivessel PCI with diffuse coronary disease. No differences were detected in the number of LEPAD lesions between groups. For the primary efficacy endpoint, the incidence of MACE at one year was 37.8% in the concomitant group vs. 34.4% in the deferred group (HR 1.20, 95% CI 0.64-2.10; p = 0.61). No significant differences were found in CIN occurrence between the concomitant and deferred groups (11.1% vs. 8.9%; OR 1.30; 95% CI 0.36-4.21; p = 0.68). Conclusions. Multisite vascular disease patients eligible for CAD and LEPAD percutaneous revascularization exhibited a high cardiovascular risk profile with diffuse multivessel coronary and lower extremity disease. Our study suggests the efficacy and safety of concomitant coronary and lower extremity percutaneous revascularization based on one-year MACE incidence and in-hospital CIN. However, dedicated studies are warranted to confirm the short- and long-term outcomes of the concomitant revascularization strategy.

SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/-) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/- mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers.

Venous Thromboembolism and Cancer: A Comprehensive Review from Pathophysiology to Novel Treatment.

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk-benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug-drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.

Focal reduction in left ventricular 123I-metaiodobenzylguanidine uptake and impairment in systolic function in patients with Anderson-Fabry disease.

BACKGROUND: Abnormalities of cardiac sympathetic innervation have been demonstrated in Anderson-Fabry disease (AFD). We aimed to investigate the relationship between regional left ventricular (LV) denervation and regional function abnormalities. METHODS: Twenty-four AFD patients (43.7 ± 12.8 years) were studied by 123I-metaiodobenzylguanidine (MIBG) cardiac imaging and speckle-tracking echocardiography. Segmental tracer uptake was estimated according to 0 to 4 score, and total defect score (TDS) was calculated for each patient. RESULTS: Segmental longitudinal strain worsened as MIBG uptake score increased (P < 0.001). By ROC analysis, a segmental longitudinal strain > - 16.2% predicted a segmental MIBG uptake score ≥1, with 79.7% sensitivity and 65.3% specificity. Segmental MIBG uptake defects were found in 13 out 24 AFD patients. LV mass index (60.8 ± 10.1 vs. 41.4 ± 9.8 g/h2.7), relative wall thickness (0.51 ± 0.06 vs. 0.40 ± 0.06), systolic pulmonary artery pressure (35.2 ± 6.7 vs. 27.2 ± 4.2 mmHg), and longitudinal strain (- 14.3 ± 2.7 vs. -19.4 ± 1.8%) were significantly higher in patients with segmental defect (all P < 0.01). At multivariate linear regression analysis, global longitudinal strain was independently associated with TDS (B = 3.007, 95% confidence interval 1.384 to 4.630, P = 0.001). CONCLUSIONS: Reduced cardiac MIBG uptake reflects the severity of cardiac involvement in AFD patients. LV longitudinal function impairment seems to be an earlier disease feature than regional myocardial denervation.

Does left ventricular function predict cardiac outcome in Anderson-Fabry disease?

In Anderson-Fabry disease (AFD) the impact of left ventricular (LV) function on cardiac outcome is unknown. Noninvasive LV pressure-strain loop analysis is a new echocardiographic method to estimate myocardial work (MW). We aimed to evaluate whether LV function was associated with outcome and whether MW had a prognostic value in AFD. Ninety-six AFD patients (41.8 ± 14.7 years, 43.7% males) with normal LV ejection fraction were retrospectively evaluated. Inclusion criteria were sinus rhythm and ≥ 2-year follow-up. Standard echocardiography measurements, myocardial mechano-energetic efficiency (MEE) index, global longitudinal strain (GLS) and MW were evaluated. Adverse cardiac events were defined as composite of cardiac death, malignant ventricular tachycardia, atrial fibrillation and severe heart failure development. During a median follow-up of 63 months (interquartile range 37-85), 14 events occurred. Patient age, cardiac biomarkers, LV mass index, left atrium volume, E/Ea ratio, LV ejection fraction, MEE index, GLS and all MW indices were significantly related to adverse outcome at univariate analysis. After adjustment for clinical and echocardiographic parameters, which were significant at univariate analysis, GLS and MW resulted independent predictors of adverse events (p < 0.01). By ROC curve analysis, constructive MW ≤ 1513 mmHg% showed the highest sensitivity and specificity in predicting adverse outcome (92.9% and 86.6%, respectively). MW did not improve the predictive value of a model including clinical data, LV diastolic function and GLS. LV function impairment (both systolic and diastolic) is associated with adverse events in AFD. MW does not provide additive information over clinical features and systolic and diastolic function.

Impact of chronic kidney disease on platelet aggregation in patients with acute coronary syndrome.

AIMS: Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy, included the more potent P2Y12 inhibitors. METHODS: We enrolled 206 patients with ACS, divided in two groups, according to the presence or the absence of moderate/severe CKD. Platelet aggregation was performed with light transmission aggregometry and results are expressed as percentage of maximum platelet aggregation. High residual platelet reactivity (HRPR) was defined as maximum platelet aggregation more than 59%. RESULTS: Patients with CKD [estimate glomerular filtration rate (eGFR) < 60 ml/min/1.73 m, n = 28] were prevalent older, diabetic, had previous coronary revascularization. In these patients, platelet aggregation was significantly higher than in those with eGFR ≥ 60 ml/min/1.73 m (ADP 10 µmol/l: 28.46 ±â€Š26.19 vs. 16.64 ±â€Š12.79, P < 0.001; ADP 20 µmol/l: 30.07 ±â€Š25.89 vs. 17.46 ±â€Š12.82, P < 0.001). HRPR was observed in 4.4% of patients, with higher prevalence in those with eGFR less than 60 ml/min/1.73 m [21.4 vs. 1.7%, P < 0.001, odds ratio (OR) [95% confidence interval (CI)] = 15.91 (3.71-68.17), P < 0.001]. At multivariate analysis, after correction for baseline confounders, eGFR [adjusted OR (95% CI) = 0.95 (0.91-0.98), P = 0.007], together with the use of clopidogrel [adjusted OR (95% CI) = 23.59 (4.01-138.82), P < 0.001], emerged as determinants of HRPR. CONCLUSION: In patients with ACS receiving dual antiplatelet therapy, CKD is associated with an increasing ADP-induced platelet aggregation and higher prevalence of HRPR, which is mainly correlated to clopidogrel use.

Left ventricular radial strain impairment precedes hypertrophy in Anderson-Fabry disease.

In Anderson-Fabry disease (AFD), left ventricular (LV) radial function has been scarcely investigated. We hypothesized that LV function may be affected by disease specific mechanisms and sought to comprehensively evaluate LV radial, circumferential and longitudinal function in a large population of AFD patients looking at the influence of LV geometry and fibrosis. We prospectively studied 94 consecutive AFD patients (41.5 ± 14.5 years; 41 men) with preserved LV ejection fraction (EF) utilizing speckle-tracking echocardiography. A subset of patients underwent gadolinium-enhanced cardiac magnetic resonance. Cases were compared to 48 healthy subjects matched for age and sex. LV concentric hypertrophy was found in 33 AFD patients while LV concentric remodeling (relative wall thickness ≥ 0.43) in 16 out 61 patients with normal LV mass. AFD patients had lower radial, longitudinal and circumferential strains than controls, independently by LV geometry pattern. Patients with LV hypertrophy showed reduced global longitudinal strain (p < 0.001) and early diastolic untwisting rate (p = 0.002) as compared to patients with normal geometry. In the whole AFD population, neither radial strain nor circumferential strain correlated with LV mass, while global longitudinal strain and early diastolic untwisting rate did (both p < 0.001). Late gadolinium enhancement was significantly associated with longitudinal strain, twisting rate and early diastolic untwisting rate, with twisting rate being the most powerful independent predictor (ß = - 0.461; p = 0.002). Findings demonstrate impairment of LV radial strain in AFD patients with preserved EF, even in a pre-hypertrophic stage. Development of LV hypertrophy and fibrosis make worse mostly longitudinal dysfunction.

Left ventricular dysfunction in ADPKD and effects of octreotide-LAR: A cross-sectional and longitudinal substudy of the ALADIN trial.

BACKGROUND AND AIM: In autosomal dominant polycystic kidney disease (ADPKD) cardiac abnormalities have been observed before the onset of hypertension or renal dysfunction. We sought to characterize, in ADPKD patients, left ventricular (LV) function and its changes after somatostatin-analogue octreotide-LAR treatment. METHODS: In a 1:1:1 cross-sectional study, we evaluated LV function by speckle-tracking echocardiography in 34 ADPKD patients from one ALADIN-trial center and in 34 age- and gender-matched healthy controls and 34 equally-matched renal controls with non-cystic chronic kidney disease. Changes in LV function were compared in the 16 and 18 ADPKD patients originally randomized to 3 year-treatment with octreotide-LAR or placebo, respectively. RESULTS: LV twist and untwisting rates were lower in ADPKD patients that in healthy or renal controls (6.1 ±â€¯2.6° vs. 11.1 ±â€¯2.1° and 10.2 ±â€¯3.7°; -49.5 ±â€¯18.1°/s vs. -79.8 ±â€¯12.2°/s and -84.3 ±â€¯25.9°/s, respectively, all p < 0.001). The correlation between LV mass or diastolic BP and untwisting rate was positive in ADPKD patients (r = 0.38, p = 0.025 and r = 0.44, p = 0.011, respectively), not significant in healthy controls and negative in renal controls (r = -0.38; p = 0.023 and r = -0.40, p = 0.012, respectively. LV untwisting rate improved from -49.9 ±â€¯18.6°/s to -70.3 ±â€¯27.5°/s with octreotide-LAR, but did not change with placebo (p = 0.027 for treatment effect). At adjusted linear regression analysis, octreotide-LAR therapy emerged as the only independent predictor of untwisting rate improvement at final visit [beta coefficient -0.504 (95% CI -46.905--6.367), p = 0.014]. CONCLUSIONS: In ADPKD patients LV function is early impaired. Somatostatin-analogue therapy might help in preventing or ameliorating LV dysfunction in this population. Clinical Trial Registration http://www.clinicaltrials.gov, NCT0030928.

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-), Akap1 heterozygous (Akap1+/-), and their wild-type (wt) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2) knockout mice (Siah2-/-). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

Effects of Carvedilol Versus Metoprolol on Platelet Aggregation in Patients With Acute Coronary Syndrome: The PLATE-BLOCK Study.

Platelet aggregation plays a pivotal role in acute coronary syndrome (ACS). In this setting, ß-blockers (BBs) are used to counteract the effects of catecholamines on heart. Circulating catecholamines can also potentiate platelet reactivity, mainly through α2- and ß2-adrenoceptors on human platelets' surface, thus BB may affect platelet aggregation; however, the effects of different BBs on platelet aggregation in contemporary-treated patients with ACS have been poorly investigated. One hundred patients with ACS on dual antiplatelet therapy with aspirin and ticagrelor were randomized to receive treatment with carvedilol, a nonselective BB (n = 50), or metoprolol, a selective ß1-blocker (n = 50), at maximum tolerated dose. Light transmission aggregometry was performed at randomization (T0) and at 30-day follow-up (T30), and the results were expressed as a percentage of maximum platelet aggregation (MPA). The primary end point was epinephrine-induced MPA at 30 days. Patients were predominantly men (80%), and mean age was 57.3 ± 9.7 years. The 2 randomized groups were well balanced for baseline characteristics. At T0, mean MPA was similar between the groups (18.96 ± 9.05 vs 18.32 ± 9.21 with 10 µM epinephrine, 14.42 ± 9.43 vs 15.98 ± 10.08 with 20 µM adenosine diphophate (ADP), and 13.26 ± 9.83 vs 14.30 ± 9.40 with 10 µM ADP for carvedilol and metoprolol, respectively, all p = NS). At 30 days, platelet aggregation induced by epinephrine was significantly lower in the carvedilol group than in the metoprolol group (23.52 ± 10.25 vs 28.72 ± 14.37, p = 0.04), with a trend toward the lower values of ADP-induced MPA (20 µM ADP 19.42 ± 13.84 vs 24.16 ± 13.62, p = 0.09; 10 µM ADP 19.12 ± 12.40 vs 22.57 ± 13.59, p = 0.19). In conclusion, carvedilol, a nonselective BB, reduces residual platelet reactivity in patients with ACS compared with the selective BB, metoprolol.

Early Cardiac Involvement Affects Left Ventricular Longitudinal Function in Females Carrying α-Galactosidase A Mutation: Role of Hybrid Positron Emission Tomography and Magnetic Resonance Imaging and Speckle-Tracking Echocardiography.

BACKGROUND: Hybrid 18F-fluorodeoxyglucose (FDG) positron emission tomography and magnetic resonance imaging may differentiate mature fibrosis or scar from fibrosis associated to active inflammation in patients with Anderson-Fabry disease, even in nonhypertrophic stage. This study was designed to compare the results of positron emission tomography and magnetic resonance cardiac imaging with those of speckle-tracking echocardiography in heterozygous Anderson-Fabry disease females. METHODS AND RESULTS: Twenty-four heterozygous females carrying α-galactosidase A mutation and without left ventricular hypertrophy underwent cardiac positron emission tomography and magnetic resonance using 18F-FDG for glucose uptake and 2-dimensional strain echocardiography. 18F-FDG myocardial uptake was quantified by measuring the coefficient of variation (COV) of the standardized uptake value using a 17-segment model. Focal 18F-FDG uptake with COV >0.17 was detected in 13 patients, including 2 patients with late gadolinium enhancement at magnetic resonance. COV was 0.30±0.14 in patients with focal 18F-FDG uptake and 0.12±0.03 in those without (P<0.001). Strain echocardiography revealed worse global longitudinal systolic strain in patients with COV >0.17 compared with those with COV ≤0.17 (-18.5±2.7% versus -22.2±1.8%; P=0.024). For predicting COV >0.17, a global longitudinal strain >-19.8% had 77% sensitivity and 91% specificity and a value >2 dysfunctional segments 92% sensitivity and 100% specificity. CONCLUSIONS: In females carrying α-galactosidase A mutation, focal 18F-FDG uptake represents an early sign of disease-related myocardial damage and is associated with impaired left ventricular longitudinal function. These findings support the hypothesis that inflammation plays an important role in glycosphingolipids storage disorders.

Outcomes after non-cardiac surgery: mortality, complications, disability, and rehospitalization.

In the last 25 years, the number of patients aged ≥75 years undergoing non-cardiac surgery has greatly increased. In elderly patients, frailty is significantly associated with an increased risk of adverse events, functional decline, procedural complications, prolonged hospitalization, and mortality. The relationship between frailty and increased mortality and morbidity requires an appropriate tool of assessment to accurately quantify the patient's clinical and perioperative conditions. The preoperative evaluation of elderly patients candidate for non-cardiac surgery should include assessment of frailty, sarcopenia and malnutrition, as these are related to high surgical risk. For colon-rectal surgery as also for gastric cancer surgery, especially early gastric cancer, the introduction of laparoscopy has yielded considerable benefits in terms of short-term postsurgical outcomes, e.g. lower rate of intraprocedural bleeding and reduced length of hospital stay. Despite the progress made in preoperative assessment, surgical procedures and postoperative management, the improvement of outcomes after non-cardiac surgery in elderly patients remains a challenge and calls for future, well-designed clinical studies.

Evolution of surgical techniques for a progressive risk reduction.

Advanced age is a strong predictor of high perioperative mortality in surgical patients and patients aged 75 years and older have an elevated surgical risk, much higher than that of younger patients. Progressive advances in surgical techniques now make it possible to treat high-risk surgical patients with minimally invasive procedures. Endovascular techniques have revolutionized the treatment of several vascular diseases, in particular carotid stenosis, aortic pathologies, and severely incapacitating intermittent claudication or critical limb ischemia. The main advantages of the endovascular approach are the low complication rate, high rate of technical success and a good clinical outcome. Biliary stenting has improved the clinical status of severely ill patients with bile duct stricture before major surgery, and represents a good palliative therapy in the case of malignant biliary obstruction.

Abluminal-Coated Drug-Eluting Bifurcation-Dedicated Stent for the Treatment of Tibioperoneal Bifurcation.

Endovascular treatment of below-the-knee region disease is often challenging because of the involvement of arterial bifurcations. Several cases have been reported on the use of coronary stents for the treatment of these patients, but limited evidence is available on the use of dedicated coronary bifurcation devices. We here report the endovascular treatment of a symptomatic bifurcation lesion in below-the-knee region, using a self-expanding Biolimus A9-eluting stent in combination with a "conventional" coronary drug-eluting stent.

Use of statins in lower extremity artery disease: a review.

BACKGROUND: Lower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk. DESCRIPTION: It is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached. CONCLUSIONS: Our opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statins.

Abdominal aortic aneurysm in patients affected by intermittent claudication: prevalence and clinical predictors.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a frequent cause of death among elderly. Patients affected by lower extremity peripheral arterial disease (LE-PAD) seem to be particularly at high risk for AAA. We aimed this study at assessing the prevalence and the clinical predictors of the presence of AAA in a homogeneous cohort of LE-PAD patients affected by intermittent claudication. METHODS: We performed an abdominal ultrasound in 213 consecutive patients with documented LE-PAD (ankle/brachial index ≤ 0.90) attending our outpatient clinic for intermittent claudication. For each patient we registered cardiovascular risk factors and comorbidities, and measured neutrophil count. RESULTS: The ultrasound was inconclusive in 3 patients (1.4%), thus 210 patients (169 males, 41 females, mean age 65.9 ± 9.8 yr) entered the study. Overall, AAA was present in 19 patients (9.0%), with a not significant higher prevalence in men than in women (10.1% vs 4.9%, p = 0.300). Patients with AAA were older (71.2 ± 7.0 vs 65.4 ± 9.9 years, p = 0.015), were more likely to have hypertension (94.7% vs 71.2%, p = 0.027), and greater neutrophil count (5.5 [4.5 - 6.2] vs 4.1 [3.2 - 5.5] x 10(3)/µL, p = 0.010). Importantly, the c-statistic for neutrophil count (0.73, 95% CI 0.60 - 0.86, p = 0.010) was higher than that for age (0.67, CI 0.56-0.78, p = 0.017). The prevalence of AAA in claudicant patients with a neutrophil count ≥ 5.1 x 10(3)/µL (cut-off identified at ROC analysis) was as high as 29.0%. CONCLUSIONS: Prevalence of AAA in claudicant patients is much higher than that reported in the general population. Ultrasound screening should be considered in these patients, especially in those with an elevated neutrophil count.

Ankle/brachial index to everyone.

BACKGROUND: In the last years significant attention has been paid in identifying markers of subclinical atherosclerosis or of increased cardiovascular risk. METHOD: An abnormal ankle/brachial index (ABI) identifies patients affected by lower extremity peripheral arterial disease, and even more important, represents a powerful predictor of the development of future ischemic cardiovascular events. CONCLUSIONS: In our opinion, ABI is a cardiovascular risk prediction tool with very desirable properties that might become a routine measurement in clinical practice.

Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication.

BACKGROUND: Lower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication. METHODS: 236 diabetic patients affected by LE-PAD at stage II of Fontaine's classification, with ankle/brachial index ≤ 0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses. RESULTS: No baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049). CONCLUSIONS: The present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events.

Chronic aortic dissection: still a challenge.

Chronic aortic dissections are complex lesions with a fairly predictable natural history depending on factors such as baseline aortic diameter, the degree of false lumen thrombosis, the presence of a persistent communication, an underlying connective tissue disorder, and the control of hypertension. Medical management with antihypertensive therapy including beta-blockers is the treatment of choice for all stable chronic aortic dissections. Repair is indicated in the case of complications: aortic rupture, malperfusion syndromes, symptomatic dissections, asymptomatic dissections becoming significantly aneurysmal or demonstrating a rapid growth rate. In this regard, serial imaging of the aorta is crucial to detect unstable lesions requiring surgery or an endovascular intervention. As endograft technologies improve endovascular approach may become the future standard of care.