Thomas Gerasimidis

The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability.

OBJECTIVE Osteopontin (OPN) and osteoprotegerin (OPG) are well-known vascular calcification inhibitors, which have been recently demonstrated to correlate with inflammation and cardiovascular events incidence. The aim of this cross-sectional study is to survey whether OPN and OPG are involved in carotid plaque vulnerability. For this reason, we assessed serum OPN and OPG levels in patients with carotid stenosis, and we explored their relationship with carotid plaque echogenicity and subsequent cerebrovascular ischemic events. METHODS A total of 164 Whites were selected from a large cohort of 297 subjects to participate. In particular, 114 patients (61 men, 53 women), aged 55 to 80, had recently-diagnosed ICA stenosis higher than 50%. A group of 50 age-, sex-, and body mass index (BMI)-matched healthy individuals served as healthy controls. Patients with renal failure, hypothyroidism, osteoporosis, and lipid-lowering therapy were excluded. Images of both carotids were obtained from all participants using a high-resolution color duplex ultrasound and the gray-scale median (GSM) score was calculated. Brain computed tomography (CT), and magnetic resonance imaging (MRI) scans when CT was questionable, were performed on all patients with carotid stenosis. Clinical parameters, lipid and glycemic indexes, hsCRP, fibrinogen, white blood cells (WBC) count, OPN, and OPG were measured. Independent t test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used for statistical analysis. RESULTS Among patients with carotid stenosis, 60 had history of ipsilateral stroke or TIA and positive CT or MRI findings (group A), while 54 had no neurological symptoms and negative CT and MRI scan (group B). Overall, patients with carotid stenosis showed worse lipid profile and increased waist circumference, blood pressure, hsCRP, fibrinogen, WBC count, OPN, and OPG levels compared with healthy subjects (group C) (P <.05). Statistical analysis revealed that group A had significantly lower levels of GSM than group B (57.41 +/- 38.19 vs 76.32 +/- 36.72; P = .008) and higher levels of hsCRP, OPN, and OPG than groups B and C (P < .05). Concerning the latter, biochemical markers group B showed only elevated OPG levels compared with group C (P = .038). Notably, GSM was considerably associated with serum OPN and OPG and waist circumference in patients with carotid atherosclerosis in univariate (r = -0.333; P = .032, r = -0.575; P < .001, r = -0.590; P =.006, respectively) and multiple regression analysis (R(2) = 0.445; P =.006). CONCLUSIONS The present study demonstrated elevated serum OPN and OPG levels in patients with carotid stenosis and documented an independent association between these biochemical markers, GSM and carotid-induced symptomatology. Therefore bone-matrix proteins combined with GSM could be potential markers for vulnerable carotid plaques.

Intensive Lipid-lowering Therapy Ameliorates Novel Calcification Markers and GSM Score in Patients with Carotid Stenosis

OBJECTIVES/DESIGN Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. The aim of this study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with carotid artery stenosis ameliorates novel vascular calcification inhibitors, such as osteopontin (OPN) and osteoprotegerin (OPG), and improves GSM score. METHODS Ninety-seven patients with carotid stenosis (>40%), but without indication for intervention, were treated for 6 months with atorvastatin (10mg-80mg) to target LDL<100mg/dl. Fifty-two age-and sex-matched healthy individuals served as the control group. Blood samples and GSM were obtained at the beginning and after 6 months. RESULTS Systolic blood pressure, hsCRP, fibrinogen, OPN and OPG levels differed significantly between patients with carotid stenosis and healthy controls at baseline (p<0.05). Atorvastatin treatment improved lipid profile and significantly reduced hsCRP (p=0.002), WBC count (p=0.041), OPN (p<0.001) and OPG levels (p<0.001). GSM score increased considerably after atorvastatin therapy (from 58.33+/-24.38 to 79.33+/-22.3; p<0.001) and that effect appeared related to OPN (p=0.001), OPG (p=0.013) and LDL (p=0.01) reduction. CONCLUSIONS In patients with carotid stenosis, intensive lipid-lowering therapy with statins attenuates serum OPN and OPG levels and enhances carotid plaque echogenicity, outlining their beneficial effects on plaque stability.

Endovascular Treatment of Popliteal Artery Aneurysms

OBJECTIVE To present the results of the endovascular treatment of popliteal artery aneurysms. METHODS From April 1999 to January 2002, 11 patients, aged 40-94 years, with 12 popliteal aneurysms were treated. Nine (75%) underwent an endoluminal repair, of whom three were done emergently due to an aneurysm rupture. Aneurysm diameter was 28-105 (mean 69) mm. A Hemobahn stent graft was inserted in six, Wallgraft in two and Passager in one case. RESULTS During a mean follow-up of 14 (3-31) months, four (44%) thromboses occurred: two in the early postoperative period (30 days) and two during the late postoperative period. Two of the four occluded grafts were successfully reopened, and in the one a stenosis of the distal end of the stent graft was treated with balloon dilatation. Patency rates at 1 and 12 months were 64/47% (primary patency) and 88/75% (secondary patency), respectively. CONCLUSION Initial experience with endovascular treatment of the popliteal aneurysm in high-risk patients yielded modest results. Larger number of patients and further follow-up time is necessary to evaluate the long-term results.

Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization

OBJECTIVE Atherosclerotic plaque stabilization is a promising strategy to prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have emerged as novel cardiovascular biomarkers. This open-label, prospective study aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is more effective than moderate lipid-lowering in increasing carotid plaque echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN and OPG levels in patients with moderate carotid stenosis. METHODS One hundred forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without indications for surgical intervention, were enrolled. Patients with coronary heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured at baseline and after 12 months as well as the GSM score. Independent samples t test, paired samples t test, Pearson correlation, and multiple regression analysis were used (P < .05). RESULTS There were no significant differences between groups at baseline. Three patients in group A experienced either cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent coronary angioplasty during follow-up. Group B showed a more pronounced improvement in total cholesterol and LDL-cholesterol compared with group A (P < .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001). Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater degree compared with moderate treatment. Similarly, GSM score was remarkably increased in both groups, but that augmentation was greater in group B (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to 85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely associated with GSM score changes in univariate and standard multiple regression analysis (R(2) = 0.411, P = .021). CONCLUSIONS Among patients with moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque echogenicity and reduced serum OPN and OPG levels to a greater extent than respective moderate atorvastatin therapy. Most importantly, those atorvastatin-induced effects were associated with OPN and OPG suppression in a dose-dependent manner.

Impact of Endograft Material on the Inflammatory Response After Elective Endovascular Abdominal Aortic Aneurysm Repair

The purpose of this paper is to examine the impact of endograft material on the inflammatory response after elective endovascular abdominal aortic aneurysm repair. Consecutive patients (n=22, all men, 53 to 82 years old) were divided into 2 groups according to the graft material used: In group A (n=12) the endovascular device was made of polyester and in group B (n=10) the device was made of expanded polytetrafluoroethylene (ePTFE). All patients received antiinflammatory drugs in the perioperative period. Fever, white blood cells and platelet count, serum concentrations of cytokines (interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-a], interleukin 8 [IL-8], acute-phase proteins high-sensitivity C-reactive protein [hsCRP] and alpha1-antitrypsin [a1-antitrypsin]), and complement protein (C3a) were measured preoperatively and 1, 3, 6, 24, 48, and 72 hours after aneurysm exclusion. One patient in each group had a systemic inflammatory response syndrome with 2 of the systemic inflammatory response syndrome (SIRS) criteria. No other complication associated with inflammation were present in any patient. Fever was more frequent in group A patients. Increases of white blood cells and serum concentrations of IL-6, TNF-a, hsCRP, a1-antitrypsin, and C3a and decrease of platelet count were recorded in both groups, but no statistically significant difference between them was recorded. However, serum concentrations of IL-8 were significantly higher in group A patients 24 hours postoperatively (p=0.01). No significant difference was apparent in the biological response between patients receiving a polyester or an ePTFE stent graft, except for fever and serum concentrations of IL-8.

Adipokines: a novel link between adiposity and carotid plaque vulnerability.

Eur J Clin Invest 2012; 42 (12): 1278–1286

Lack of an association between angiotensin converting enzyme gene polymorphism and peripheral arterial occlusive disease

Numerous factors have been reported to influence the pathogenesis of atherosclerosis. The angiotensin I converting enzyme (ACE) gene is a candidate gene for atherosclerotic-related disease. In the present study, the association between the polymorphism of the ACE gene and peripheral arterial occlusive disease (PAOD) was investigated. Using polymerase chain reaction techniques, 100 patients (age 66.7-7.7 years) with PAOD and 100 age-matched controls were divided into the three ACE genotypes: II, ID and DD (Insertion I and Deletion D). There was no evidence of any association between ACE gene polymorphism and the presence of PAOD (odds ratio 0.759; 95% confidence interval 0.418-1.377). These results indicate an absence of association between DD genotype and PAOD. Further evaluation in a larger population study is required to examine the possibility of an increased risk of PAOD in DD homozygotes.

The protective effect of oxygenated perfluorocarbons (PFCs) on intestinal ischemia reperfusion injury (I/R) in rabbits.

Objective: To evaluate the effect of intraluminal administration of oxygenated perfluorocarbons (PFCs) on small intestine’s viability in an experimental model of acute ischemia-reperfusion (I/R). Methods: Twenty rabbits were divided in four groups: sham-operated controls (group A), acute I/R (group B), acute I/R plus infusion of PFCs 30 min before ischemia (group C), and acute I/R plus infusion of PFCs 30 min before reperfusion (group D). Malondialdehyde (MDA) tissue levels and d-lactate blood samples were taken. All tissue sections were examined under light microscope. Results: Mean MDA levels in group A: 1.79 ± 0.97 at 0 min, 2.25 ± 1.76 at 120 min and 3.70 ± 1.76 nmols/g at 180 min. Group B: 2.60 ± 0.58 at 0 min, 4.20 ± 0.58 at 120 min and 5.48 ± 2.01 at 180 min. Group C: 1.54 ± 0.85 at 0 min, 1.14 ± 0.37 at 120 min and 0.59 ± 0.35 at 180 min. Group D: 2.12 ± 0.62 at 0 min, 3.97 ± 0.70 at 120 min and 2.32 ± 0.37 at 180 min (p < 0.05). Mean d-lactate levels in group A: at 0 min 36.45 ± 1.99, at 120 min 39.10 ± 2.37 and at 180 min 40.05 ± 2.13 mg/dl. Group B: 61.23 ± 11.03 at 0 min, 74.84 ± 10.70 at 120 min and 89.90 ± 9.29 at 180 min. Group C: at 0 min 51.05 ± 10.36, at 120 min 56.07 ± 11.27 and at 180 min 57.20 ± 11.19. Group D: 64.36 ± 5.26 at 0 min, 72.55 ± 7.19 at 120 min and 77.02 ± 9.41 at 180 min (p < 0.05). Histopathological analysis indicated a significant improvement in the groups of oxygenated PFCs compared with I/R group. Conclusion: Intraluminal administration of oxygenated PFCs seems that protect the intestine from the I/R injury.

Surgical management of primary aldosteronism. Not everything that shines is gold.

Background: Primary aldosteronism (PA) is a syndrome which includes a group of clinical entities in which aldosterone production is inappropriately high and nonsupressible by sodium loading. The most frequent causes of PA are adrenal adenoma and unilateral or bilateral primary hyperplasia. Methods: We report a case of a 55-year-old man with a 10-year history of hypertension in whom functional hormonal studies were indicative of PA. Because adrenal venus sampling was not available at our hospital, the investigation was conducted with a computed tomography (CT) scan and a scan with 131-iodocholesterol (NP-59) which both revealed a left adrenal adenoma. Results: The tumor was excised laparoscopically without any complications and the histological findings confirmed the diagnosis of an aldosterone-producing adenoma. Blood pressure remained normal despite the discontinuation of antihypertensive drugs, further supporting that the adrenal tumor was indeed the cause of high blood pressure. Unfortunately, blood pressure began to rise again 2 months later, and laboratory findings indicated the presence of PA once again. Spironolactone was instituted and blood pressure significantly improved and was finally controlled by the addition of amlodipine. Conclusion: We report this case to underline the difficulties in the discrimination between adenoma and hyperplasia in everyday clinical practice. Although the CT and scintigraphic findings strongly pointed toward an adenoma, the fact that PA re-appeared shortly after the operation, indicated that the underlying cause of the PA was hyperplasia and not adenoma after all.

Intussusception of the small bowel secondary to malignant metastases in two 80-year-old people: a case series

IntroductionSmall bowel intussusception is rare in adults and accounts for one percent of all bowel obstructions. Malignancy is the etiologic agent in approximately 50 percent of all cases.Case presentationOur first patient was an 80-year-old Caucasian woman with signs and symptoms of intermittent bowel obstruction for the last 12 months. Pre-operative investigation by abdominal computed tomography scanning revealed an obstruction at the ileocecal valve. Exploratory laparotomy revealed an ileocecal intussusception. She underwent an enterectomy. Histological examination showed metastatic breast cancer (lobular carcinoma). Our patient had previously undergone a mastectomy due to carcinoma three years earlier.Our second patient was an 80-year-old Caucasian man with signs and symptoms of acute bowel obstruction. Pre-operative investigation by abdominal computed tomography scanning showed an intussusception in the proximal part of the small bowel. Exploratory laparotomy revealed a jejunojejunal intussusception. He underwent an enterectomy. Histological examination showed metastatic melanoma. Our patient had a prior history of a primary cutaneous melanoma which was excised two years ago.ConclusionPre-operative determination of the etiologic agent of intussusception in the small bowel in adults is difficult. Although a computed tomography scan is very helpful, the diagnosis of intussusception is made by exploratory laparotomy and histological examination defines the etiologic agent. A prior malignancy in the patients history must be taken under consideration as a possible cause of intussusception.