Eugenio Laurenzano

Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function.

BACKGROUND & AIMS Peripheral arterial disease (PAD) is strongly associated with endothelial dysfunction and inflammation, which portend a high cardiovascular risk. Accordingly, we investigated the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on endothelial function and inflammatory status in affected individuals. METHODS PAD patients were randomly divided into two groups. In Group I (n=16) pre-enrollment therapy was not modified, while in Group II (n=16) n-3 PUFAs 1 g b.i.d. for 3 months were added to the previous treatment. Endothelial function was assessed by measuring plasma soluble thrombomodulin (sTM) and brachial artery flow-mediated dilation (FMD), and the inflammatory status by measuring high-sensitivity C-reactive protein and myeloperoxidase. RESULTS In Group II, n-3 PUFAs reduced sTM levels from the median value of 33.0 ng/mL (interquartile range 16.7, 37.2) to 17.0 ng/mL (11.2, 33.7) (p=0.04), and improved FMD from 6.7% (3.7, 8.7) to 10.0% (6.2, 14.2) (p=0.02). Conversely, these markers did not change in Group I. After 3 months, the levels of inflammatory markers remained unmodified in both groups. CONCLUSIONS In PAD, n-3 PUFAs induced a marked improvement in endothelial function. Conversely, they did not affect the inflammatory status. In future, large, prospective studies are needed to investigate whether n-3 PUFAs, by improving endothelial function, would reduce the incidence of ischemic events in a population at high risk.

Leukocyte count in peripheral arterial disease: A simple, reliable, inexpensive approach to cardiovascular risk prediction.

BACKGROUND An elevated leukocyte count is widely proven to predict cardiovascular risk in healthy subjects and coronary patients, but its prognostic role in peripheral arterial disease (PAD) has received scarce attention. OBJECTIVES To assess the impact of leukocyte count on the incidence of major cardiovascular events in PAD, and verify whether it adds to the prognostic power of the ankle/brachial index (ABI). METHODS The occurrence of myocardial infarction and stroke was prospectively assessed in 259 consecutive PAD patients. Receiver-operating characteristic analysis and the bootstrap approach were used to identify the best cut-offs to predict the outcome, and hazard ratios (HRs) and c-statistics to assess the ability to classify risk. RESULTS During a median follow-up of 30.0 months, 28 patients had an event. Adjusted Cox analyses performed on total and differential leukocyte counts, showed that only total leukocyte count (TLC) and neutrophil count (NC), considered as continuous variables, were associated with increased cardiovascular risk (HR=1.35, p<0.01 and HR=1.31, p<0.02, respectively). Patients with ABI < or = 0.63 plus TLC>7.7 x10(9)/L or NC>4.6 x 10(9)/L had a higher risk of about 5-fold vs patients with ABI>0.63 plus TLC< or =7.7 x 10(9)/L (p<0.01) or NC < or = 4.6 x 10(9)/L (p<0.01). The c-statistic for ABI was 0.61, similar to those for TLC (0.63) and NC (0.66). However, it significantly increased to 0.70 and 0.69 for the models incorporating ABI and TLC or ABI and NC, respectively (p<0.05 for both vs ABI alone). CONCLUSIONS TLC and NC, which are inexpensive and reliable tests, predict major cardiovascular events in PAD, and add to the prognostic power of ABI, currently the most powerful prognostic indicator in these patients.

Effects of successful percutaneous lower extremity revascularization on cardiovascular outcome in patients with peripheral arterial disease

BACKGROUND Lower extremity peripheral arterial disease (LE-PAD) reduces walking capacity and is associated with an increased cardiovascular risk. Endovascular revascularization of LE-PAD improves walking performance and quality of life. In the present study, we determined whether successful lower limbs revascularization also impacts cardiovascular outcome in LE-PAD patients. METHODS 479 consecutive LE-PAD patients at stage II of Fontaines classification, with ankle/brachial index ≤ 0.90 and one or more stenosis >50% in at least one leg artery, were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 264 (55.1%) underwent percutaneous lower extremity angioplasty (PTA group), while 215 (44.9%) were managed with conservative therapy (MT group). The incidence of major cardiovascular events (including cardiovascular death, myocardial infarction, ischemic stroke, coronary and carotid revascularizations) was prospectively analyzed by Kaplan-Meier curves. Crude and adjusted HRs (95% CI) of developing a cardiovascular event were calculated by Cox analysis. RESULTS No baseline differences were observed among the groups, except for a lower maximum walking distance in the PTA group. During a median follow-up of 21 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in PTA compared to MT patients (6.4% vs. 16.3%; p=0.003), and patients in the MT group showed a 4.1-fold increased cardiovascular risk compared to patients in the PTA group, after adjustment for potential confounders (95% CI 1.22-13.57, p=0.023). CONCLUSIONS This study shows that successful revascularization of LE-PAD patients affected by intermittent claudication, in addition to improving functional status, reduces the occurrence of future major cardiovascular events.

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

BackgroundAbdominal 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.MethodsWe 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.ResultsThe 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] x103/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 x103/μL (cut-off identified at ROC analysis) was as high as 29.0%.ConclusionsPrevalence 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.

Femoral Plaque Echogenicity and Cardiovascular Risk in Claudicants

OBJECTIVES The present study was designed to verify whether the evaluation of femoral plaque echogenicity might be a useful tool for cardiovascular risk assessment in patients affected by lower extremity peripheral arterial disease. BACKGROUND Lower extremity peripheral arterial disease is a common manifestation of atherosclerosis and is associated with a high risk of developing major cardiovascular events. Vulnerable atherosclerotic plaque plays a central role in the occurrence of acute ischemic events in different vascular territories. Furthermore, atherosclerosis is a systemic disease, and the presence of an unstable atherosclerotic plaque in a certain vascular district, characterized by low echogenicity at B-mode ultrasound, is associated to a greater prevalence of unstable plaques in other vascular beds. METHODS Femoral plaque echogenicity of 246 claudicants with ankle/brachial index ≤0.90 was evaluated at B-mode ultrasound by visual analysis and by calculating the grayscale median (GSM) value. In these patients, the occurrence of myocardial infarction and stroke was prospectively assessed. RESULTS Femoral GSM values and plaque types assessed by visual analysis were highly correlated by Spearman analysis (rho = 0.905, p < 0.001). During a median follow-up of 30 months, 32 patients (13%) had a major cardiovascular event. Compared with patients without events, those who experienced an event during the follow-up had a lower femoral plaque GSM value (42.9 ± 26.2 vs. 58.8 ± 19.3, p = 0.002) and a higher prevalence of hypoechoic femoral plaque at visual analysis (68.8% vs. 19.6%, p < 0.001). At Cox analysis, femoral GSM showed an inverse relationship with cardiovascular risk, even after adjustment for possible confounders (hazard ratio: 0.96, 95% confidence interval [CI]: 0.95 to 0.98, p < 0.001). Furthermore, patients with hypoechoic femoral plaques at visual analysis had a 7.24-fold increased cardiovascular risk compared with patients with hyperechoic plaques after adjustment for possible confounders (95% CI: 3.23 to 16.22, p < 0.001). CONCLUSIONS This study demonstrates that the presence of hypoechoic atherosclerotic femoral plaques is associated with higher cardiovascular risk in lower extremity peripheral arterial disease patients.

Metabolic syndrome and cardiovascular risk prediction in peripheral arterial disease

BACKGROUND AND AIMS Metabolic syndrome (MetS) was reported to be associated with increased cardiovascular risk in various settings, however its prognostic impact in peripheral arterial disease (PAD) is scanty. METHODS AND RESULTS We prospectively studied 173 patients with intermittent claudication and ankle/brachial index (ABI)<0.90, in whom MetS was defined using the criteria of both the revised version of the Adults Treatment Panel III (rATP III) and the International Diabetes Federation (IDF). Of these patients, 52.6% met the rATP III and 54.9% the IDF criteria for MetS. During a median follow-up of 31 months, 54 cardiovascular events occurred. Kaplan-Meier curves showed a greater incidence of ischemic events in patients with MetS than in those without. However, adjusted Cox analyses revealed that only IDF-MetS was independently associated with increased cardiovascular risk (HR=1.91, 95% CI 1.03-3.51, p=0.038). Kaplan-Meier curves for the four groups of patients delineated according to the bootstrapped ABI cut-off value (0.73) and the presence or absence of IDF-MetS revealed that the syndrome improved the predictive power of ABI alone. Actually, among patients with an ABI≤0.73, those with IDF-MetS had a higher cardiovascular risk than those without the syndrome (HR=2.55, 95% CI 1.22-5.12, p=0.012). This was confirmed by c-statistic, which was 0.56 for ABI alone and increased to 0.65 (p=0.046) when IDF-Mets was added to the pressure index. CONCLUSION In PAD, IDF-MetS, but not rATP III-MetS, is associated with an increased risk of cardiovascular events. Furthermore, IDF-MetS adds to the prognostic value of ABI, currently the most powerful prognostic indicator in PAD.

Echolucent femoral plaques entail higher risk of echolucent carotid plaques and a more severe inflammatory profile in peripheral arterial disease

OBJECTIVE Plaque instability is recognized as a multivessel phenomenon related to inflammation. This study examined if the morphology of femoral plaques was related to that of carotid plaques. METHODS The echogenicity of femoral and carotid plaques of 102 patients with peripheral artery disease (PAD) was studied and classified as echolucent or echorich according to the gray-scale median (GSM) value, which was 53.6 for femoral plaques and 55.2 for carotid plaques. Serum C-reactive protein (CRP) levels and neutrophil count were also measured. RESULTS Echolucent carotid plaques were more frequent in patients with echolucent than in those with echorich femoral plaques (55.8% vs 32.0%; P < .01). At multivariate analysis, femoral GSM lower than the median was the only significant predictor of echolucent carotid plaques (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.53-9.83). Patients with echolucent femoral plaques had higher serum CRP levels (P < .01) and a higher neutrophil count (P = .029) than patients with echorich femoral plaques. However, univariate analysis showed that neutrophil count (OR, 3.48; 95% CI, 1.23-9.85) but not hs-CRP was associated with echolucent carotid plaques. At multivariate analysis, neutrophil count exceeding the median remained associated with echolucent carotid plaques (OR, 5.71; 95% CI, 1.37-23.85), whereas the association between femoral and carotid echolucency was attenuated (OR, 3.75; 95% CI, 0.98-4.43). CONCLUSIONS In PAD, the presence of echolucent femoral plaques is associated with a greater prevalence of echolucent carotid plaques, probably as a consequence of a more pronounced inflammatory profile. This confirms and extends the finding that plaque echolucency is a multivessel phenomenon. Prospective studies are needed to assess whether carotid screening in PAD patients might contribute to improving clinical decision-making.

Prevalence of hypoechoic carotid plaques in coronary artery disease: relationship with coexistent peripheral arterial disease and leukocyte number

Abstract In coronary artery disease (CAD), a concomitant peripheral arterial disease (PAD) entails a more severe coronary atherosclerosis. We hypothesized that the severity of carotid artery disease is greater in CAD+PAD than in CAD alone. In 90 CAD and 79 CAD+PAD patients, carotid plaque echolucency was measured by gray-scale median (GSM), and the degree of carotid stenosis by routine Doppler criteria. Plaques were absent in 20 (22.2%) CAD and 8 (10.1%) CAD+PAD patients (p = 0.035), while the prevalence of carotid stenosis ≥ 50% was 16.7% and 25.3%, respectively (p = 0.166). The GSM score was 45.1 [21.7–67.7] in CAD+PAD vs 60.1 [44.9–83.1] in CAD alone (p < 0.001). Consistently, hypoechoic plaques (GSM < 25th percentile) were more common in CAD+PAD than in CAD patients (38.0% vs 11.4%, p < 0.001). On multivariate analysis, CAD+PAD was the only variable significantly associated with hypoechoic plaques (OR = 4.16, 95% CI 1.68–10.28). However, when the leukocyte count was added to the model, it showed the strongest association with hypoechoic plaques (OR = 6.70, 95% CI 2.13–21.10). In conclusion, compared with CAD alone patients, those with concomitant PAD showed a greater prevalence of plaques with characteristics of instability. Thus, our data suggest that in CAD+PAD, evaluation of carotid plaque echogenicity could contribute to improve clinical decision-making and differentiate treatments for individual patients.

Early outcome of high energy Laser (Excimer) facilitated coronary angioplasty ON hARD and complex calcified and balloOn-resistant coronary lesions: LEONARDO Study

AIM An innovative xenon-chlorine (excimer) pulsed laser catheter (ELCA X80) has been recently used for the treatment of complex coronary lesions, as calcified stenosis, chronic total occlusions and non-compliant plaques. Such complex lesions are difficult to adequately treat with balloon angioplasty and/or intracoronary stenting. The aim of this study was to examine the acute outcome of this approach on a cohort of patients with coronary lesions. METHODS AND RESULTS Eighty patients with 100 lesions were enrolled through four centers, and excimer laser coronary angioplasty was performed on 96 lesions (96%). Safety and effectiveness data were compared between patients treated with standard laser therapy and those treated with increased laser therapy. Laser success was obtained in 90 lesions (93.7%), procedural success was reached in 88 lesions (91.7%), and clinical success in was obtained in 87 lesions (90.6%). There was no perforation, major side branch occlusion, spasm, no-reflow phenomenon, dissection nor acute vessel closure. Increased laser parameters were used successfully for 49 resistant lesions without complications. CONCLUSIONS This study suggests that laser-facilitated coronary angioplasty is a simple, safe and effective device for the management of complex coronary lesions. Furthermore, higher laser energy levels delivered by this catheter improved the device performance without increasing complications.

The prevalence of hypoechoic carotid plaques is greater in peripheral than in coronary artery disease and is related to the neutrophil count

OBJECTIVE Previous reports indicate that the prevalence and severity of carotid stenoses is greater in peripheral artery disease (PAD) than in coronary artery disease (CAD). To date, no study has compared these two populations with respect to plaque echogenicity, which is an independent risk factor for cerebrovascular events. METHODS In 43 PAD patients without CAD and in 43 CAD patients without PAD, carotid plaques were studied with high-resolution B-mode ultrasound and by computerized measurement of the gray-scale median. RESULTS At visual analysis, the prevalence of hypoechoic plaques was 39.5% in PAD and 18.6% in CAD (P = .033). The corresponding values for gray-scale median analysis were 34.9% and 14.0% (P = .024). At multivariate analysis, PAD patients showed a greater risk of having hypoechoic plaques than CAD patients at visual (odds ratio [OR], 4.39, 95% confidence interval [CI] 1.21-15.92, P = .025) and gray-scale median analysis (OR, 5.13; 95% CI, 1.27-20.67; P = .021). This association was no longer significant when neutrophil number was included among the covariates. In this model, only an increased neutrophil count was associated with hypoechoic plaques (P < .01 for both visual and gray-scale median analysis). Indeed, neutrophil count was greater in PAD than in CAD (4.4 +/- 1.0 vs 3.9 +/- 1.2 10(9)/L, P = .030). The concordance between visual typing of carotid plaques and gray-scale median measurement was good (rho = 0.714, P < .01). CONCLUSIONS Compared with CAD patients, those with PAD, in addition to a greater atherosclerotic burden, may have characteristics of instability of carotid plaques that, in turn, may result in cerebrovascular events. Prospective studies are needed to assess specifically whether the greater prevalence of hypoechoic plaques in PAD vs CAD patients is associated with a greater risk of cerebrovascular events.