Maria Alepaki

Arterial stiffness and novel biomarkers in patients with abdominal aortic aneurysms

OBJECTIVES Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with inflammation, and cardiovascular events incidence. We investigated the association of PWV with the aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA). METHODS We enrolled 108 men with AAA (AAA group) candidates for endovascular repair. We excluded patients with Marfan syndrome or other collagen-related disorders. Forty-one age-matched men, with stable coronary artery disease (CAD), but without AAA, served as controls (CO group). PWV, clinical parameters and serum levels of osteoprotegerin (OPG), osteopontin (OPN), interleukin-6 (IL-6) and IL-10 were determined. RESULTS With the exception of higher smoking rate and the lower statins usage in the AAA group, there were non-significant differences in the rest of demographic and clinical parameters (p>0.05). We found significantly higher levels of PWV in AAA than CO group (12.99±3.75 m/s vs 10.03±1.57 m/s, p<0.001). In parallel, serum OPG, OPN, IL-6 levels were considerably increased, while IL-10 levels were downregulated (p<0.001) in AAA group. PWV positively correlated with mean blood pressure, OPG concentrations and AAA diameter in univariate and multivariate analysis (R(2)=0.498, p=0.008). Finally, age and OPG remained independent determinants of AAA presence in the whole study cohort. CONCLUSIONS Arterial stiffness, circulating vascular calcification inhibitors and inflammatory mediators seem to be significantly upregulated in patients with AAA. An independent association of PWV with mean blood pressure, OPG and AAA diameter is of clinical importance which requires further investigation.

Changes in aortic pulse wave velocity of patients undergoing endovascular repair of abdominal aortic aneurysms.

Purpose To assess changes in pulse wave velocity (PWV), a valid index of arterial stiffness, in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). Arterial stiffness is an independent marker of all-cause mortality and cardiovascular morbidity and mortality. Methods Forty-eight consecutive male patients (mean age 71 ± 4 years) underwent elective EVAR (AAA group) after exclusion of patients with Marfan syndrome or other collagen-related disorders. Thirty-one age-matched men (mean age 69 ± 5 years) without overt cardiovascular disease served as controls. PWV and clinical parameters were determined at baseline in both groups and after 6 months in the AAA group. Results At baseline, the groups did not differ in demographic characteristics, lipid profile, or blood pressure levels (p>0.05). PWV was considerably higher in AAA than controls (p<0.001). PWV positively correlated with mean blood pressure, AAA diameter, and age in univariate and multivariate analysis (R 2 =0.498, p=0.008). At 6 months after EVAR, PWV significantly increased from 13.11 ± 3.57 m/s to 16.41 ± 2.33 m/s (p<0.001) in the AAA group. Conclusion Patients with AAA present with significantly elevated PWV levels compared to controls, and stent-graft repair is associated with a significant increase in the PWV. Whether those changes contribute to the cardiovascular risk in AAA patients needs further investigation.

Differential effects of stent-graft fabrics on arterial stiffness in patients undergoing endovascular aneurysm repair.

Purpose: To evaluate the differential effects of endograft fabric types on pulse wave velocity (PWV), a valid, clinically feasible marker of arterial stiffness, in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs). Methods: As part of a registered study (ClinicalTrials.gov identifier NCT00636766), 118 consecutive men (mean age 71±8 years) with AAA undergoing elective EVAR were divided into groups according to the type of fabric in the implanted endografts: 46 had polytetrafluoroethylene (PTFE)-covered stent-grafts and 72 received stent-grafts covered with polyester fabric. Patients with Marfan syndrome, collagen-related disorders, and end-stage renal failure were excluded. PWV, clinical characteristics (comorbidities, body mass index, blood pressure, lipids, and glucose profile), novel biomarkers [interleukin (IL)-6, IL-8, IL-10, and osteoprotegerin (OPG)] were determined at baseline and prospectively after 12 months. Results: At baseline, standard multiple regression analysis revealed the independent association of mean blood pressure, OPG, and AAA diameter with PWV after adjustment for age (R2=0.729, p=0.036). At follow-up, serum levels of both IL-8 and IL-10 were significantly increased, while OPG decreased in both groups (p<0.05). However, between-group comparison revealed a more adverse effect of polyester covered endografts on serum IL-8 (p<0.001) and OPG (p=0.048) levels. At the same time, PWV was considerably increased in both polyester (+4.12±0.33 m/s, p<0.001) and PTFE (+2.82=0.25 m/s, p=0.003) groups; the effect was more pronounced in the former group (p=0.033). In multivariate analysis, the polyester endograft type emerged as an independent determinant of PWV change after EVAR (R2=0.460, p=0.040). Conclusion: Both endograft types increased PWV, while recipients of polyester covered stent-grafts showed greater PWV elevation. Further investigation will clarify the inflammatory response and the differential clinical impact of endograft types.

The diagnostic accuracy of two methods for E6&7 mRNA detection in women with minor cytological abnormalities

Objective. To examine the diagnostic accuracy of nucleic acid sequence based amplification (NASBA) and flow cytometry for E6&7 human papillomavirus (HPV) mRNA detection in the triage of minor cytological abnormalities. Design. Prospective diagnostic accuracy study. Setting. Gynecology outpatient clinics of a university hospital. Population. 472 women with low‐grade squamous intraepithelial lesion (LSIL) or atypical squamous cells of undetermined significance (ASCUS). Methods. Residual material of the liquid‐based smears was tested by NASBA and by flow cytometry for E6&E7 mRNA expression. Histological diagnosis was used as reference standard. Main outcome measures. Accuracy indices of the two techniques and of type 16‐specific NASBA for the detection of cervical intraepithelial neoplasia (CIN) 2+ and CIN3+, accuracy indices at age >35 years, correlation between NASBA and flow, comparison between integrated and episomal high‐risk HPV infection for risk of CIN2+. Results. Both tests showed increased positivity rates with increasing severity of the lesion (p < 0.05, chi‐squared test for trend). There was a positive correlation between NASBA and flow results (phi coefficient = 0.325). NASBA‐positive cases were more likely to have CIN2+ than were NASBA‐negative/DNA‐positive for types 16, 18, 31, 33, 45 (25/73 vs. 4/52, p= 0.0004; Fisher‘s exact test). In the LSIL group the NASBA accuracy indices for CIN3+ were: sensitivity 75%, specificity 78.7% and positivity rate 20.8%, and for flow 77.8%, 64.5% and 35.9%, respectively. Conclusions. NASBA has favorable specificity and positivity rates for triaging LSIL prior to colposcopy. A relatively low sensitivity warrants cytological surveillance of the NASBA‐negative LSILs. Flow cytometry does not perform as well overall.

Promoter Methylation of p16INK4A, hMLH1, and MGMT in Liquid-Based Cervical Cytology Samples Compared with Clinicopathological Findings and HPV Presence

Cervical cancer is a common cancer inflicting women worldwide. Even though, persistent infection with oncogenic Human Papillomavirus (HPV) types is considered the most important risk factor for cervical cancer development, less than 5% of women with HPV will eventually develop cervical cancer supporting that other molecular events, like methylation-dependent inactivation of tumor suppressor genes, may cocontribute in cervical carcinogenesis. We analyzed promoter methylation of three candidate genes (p16, MGMT, and hMLH1) in 403 liquid-based cytology samples. Methylation was commonly identified in both benign and pathologic samples and correlated with higher lesion grade determined by cytological, colposcopical, or histological findings, with HPV DNA and mRNA positivity of specific HPV types and p16INK4A protein expression. Overall accuracy of methylation is much lower than traditional diagnostic tests ranking it as an ancillary technique with more data needed to identify the exact value of methylation status in cervical carcinogenesis.

Inflammatory Response and Renal Function Following Endovascular Repair of the Descending Thoracic Aorta

Purpose: To evaluate inflammatory response and renal function after thoracic endovascular aortic repair (TEVAR) of lesions in the descending thoracic aorta. Methods: Thirty-two consecutive patients treated with TEVAR from January 2010 to August 2013 were enrolled in this prospective study. Two were excluded owing to dissecting thoracic aortic aneurysm (TAA) extending into the renal arteries with renal failure in one and a saccular TAA in which a multilayer flow-modulating stent was implanted in the other. This left 30 patients (28 men; mean age 68.8±5.9 years) with 28 TAAs, an aortic dissection, and an aortic ulcer for the analysis. Temperature and serum levels of white blood cells (WBCs), C-reactive protein (CRP), interleukin-10 (IL-10), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), creatinine, urea, and cystatin C were measured preoperatively and at 24 and 48 hours postoperatively. Results: Statistically significant increases in temperature and serum levels of WBCs, CRP, IL-10, and IL-6 were observed 24 and 48 hours postoperatively compared to baseline (all p<0.05). The number of endografts and the coverage of the celiac or subclavian artery did not affect the magnitude of the inflammatory response. No significant differences were observed concerning serum levels of IL-8, TNF-α, creatinine, or cystatin C from baseline to 24 or 48 hours postoperatively. Conclusion: Endograft implantation in the thoracic aorta may propagate an inflammatory response during the early postoperative period. No clinical adverse events related to the increased inflammatory response were observed. Renal function does not seem to be deteriorated after TEVAR in the descending thoracic aorta.