Association between serum levels of pro-metalloproteinase 1, tissue inhibitor of metalloproteinases 1 and 2 and prevalent cardiovascular disease in a population-based study.

AIM: The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events. METHODS: Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models. RESULTS: Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (P(for trend)=0.006 and P=0.001, respectively) and inflammatory factors (P(for trend)=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (OR(adjusted)=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >1000 ng/mL had a 75% reduced odds for CVD compared to the rest (OR(adjusted)=0.25; 95% CI=0.11 to 0.60; P(for trend)=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease. CONCLUSION: A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.

Plaque area at carotid and common femoral bifurcations and prevalence of clinical cardiovascular disease.

AIM: Different ultrasonic arterial wall measurements have been used as predictors of future myocardial infarction or stroke. The aim of the present study was to determine the relationship of total plaque area (TPA) (the sum of the atherosclerotic plaque area measurements from both carotid and both common femoral arteries) with prevalence of cardiovascular disease in a population-based cross-sectional study and compare it with intima-media thickness (IMT). METHODS: Seven hundred sixty-two individuals (47% male) over the age of 40 were screened for cardiovascular risk factors. RESULTS: Evidence of clinical cardiovascular disease was present in 113 (14.8%). Both carotid and both common femoral bifurcations were scanned with ultrasound. After adjustment for conventional risk factors the association of IMT with prevalence of clinical cardiovascular disease was low (P=0.84, OR of upper IMT quintile 1.36; 95% CI 0.56 to 3.26) and of TPA high (P<0.001, OR of upper TPA quintile 8.38; 95% CI 2.57 to 27.32). TPA greater than 42 mm2 (cut-point derived from ROC curve analysis) identified 266 (34.9%) of the population that contained 87/113 (76.9%) of the clinical events (sensitivity: 77%; specificity: 73%; positive predictive value: 33%; negative predictive value: 94%; positive likelihood ratio of 2.79). In contrast, IMT greater than 0.07 mm had a sensitivity, specificity, positive and negative predictive value and positive likelihood ratio of 68%, 60%, 23%, 91% and 1.69 respectively. CONCLUSION: Total plaque area appears to be more strongly associated with the prevalence of cardiovascular disease than IMT. This finding warrants further prospective studies.

Leukocyte telomere length is associated with measures of subclinical atherosclerosis.

AIMS: Our aim was to test the association of mean leukocyte telomere length (LTL) with ultrasonic measures of subclinical atherosclerosis such as intima-media thickness in the common carotid (IMTcc) and sum of plaque areas (SPA) and with serological markers. METHODS AND RESULTS: Carotid and femoral bifurcations were scanned in 762 general population volunteers (46% men) over 40. Four features were considered: (a) IMTcc, (b) sum plaque areas of carotid plaques (SPAcar), (c) sum plaque area of common femoral plaques (SPAfem) and (d) sum plaque area (SPA--sum of the plaque areas of the largest plaques present in each of both carotid and femoral bifurcations). Mean LTL was determined with a quantitative real-time PCR-based method. IMTcc was strongly associated with mean LTL both before and after correction for traditional risk factors (B=-0.002; 95% CI=-0.004 to -0.00; p=0.014). In sex-specific analysis, the association was stronger in men (p for sex interaction<0.001). SPAfem was associated with LTL in women before and after correction (B=-0.195; 95% CI=-0.38 to -0.01; p=0.037) (p for sex interaction<0.001). LTL was also associated with age and sex-adjusted levels of hsCRP (p=0.012), sCD40L (p=0.042), homocysteine (p=0.006), creatinine (p=0.02), ApoA1 (p=0.01), Lp(a) (p=0.04) and HOMA-IR (p=0.008). CONCLUSIONS: Our results support the telomere hypothesis and highlight potential differences in the biological mechanisms leading to intima-media thickening and/or plaque formation between vascular beds. They may provide insights into a novel treatment of antisenescence to prevent atherosclerosis.

Cost benefit of intermittent pneumatic compression for venous thromboembolism prophylaxis in general surgery.

AIM: In moderate to high-risk general surgical patients, the cost effectiveness of mechanical prophylaxis for venous thromboembolism (VTE) is uncertain. Therefore, we determined the costs and savings of intermittent pneumatic compression (IPC) plus graduated compression stockings (GCS). METHODS: Postoperative VTE events in the absence of prophylaxis, efficacy of prophylaxis and costs of prophylaxis have been obtained from the English literature and Medicare 2004 reimbursement schedule. RESULTS: In 1000 moderate to high risk general surgical patients, in the absence of prophylaxis, the cost of investigating and treating 72 patients with clinical suspicion of DVT and 32 with PE is calculated to be $263,779. This corresponds to a cost of $263 per surgical patient. The cost of IPC combined with TED stockings in 1000 similar patients would be $66 760, and the cost of diagnosis and treatment of the reduced numbers (69% reduction) of clinical VTE is $ 83,574 making a total of $150 344. This means a saving of $133,435 ($263,779 - $150,344) per 1000 patients. This corresponds to a saving of $113 per surgical patient. Sensitivity analysis demonstrates that despite variation in costs or efficacy for IPC plus GCS, marked savings persist. CONCLUSIONS: Prophylaxis with IPC not only prevents VTE but also saves money.

ApoB/ApoA1 ratio and subclinical atherosclerosis.

AIM: It has been demonstrated that an increased apolipoprotein B (ApoB)/apolipoprotein A-I (ApoA1) ratio is associated with atherogenic low density lipoprotein (LDL) particles and the development of clinical cardiovascular disease. The aim of this study was to test the hypothesis that ApoB/ApoA1 ratio is associated with early subclinical atherosclerosis as demonstrated by ultrasonic measurements. METHODS: Both common carotid and common femoral bifurcations have been scanned with high-resolution ultrasound in 767 volunteers over the age of 40. The latter consisted of 95% of the population of two randomly selected areas. IMTcc, IMTmax (including plaques), total plaque thickness (TPT) (the sum of the thickest plaques present at each bifurcation in cm) and black plaque burden (BPB) (TPT means plaque type) using the Widder classification with type 1 being the most hyperechoic and calcified and type 5 the most hypoechoic plaque were recorded. A medical history was taken with emphasis on risk factors present and a fasting lipid profile including ApoB and ApoA1 was determined. RESULTS: In the total population (N.=767) the mean (+/-SD) ApoB/ApoA1 ratio was 0.85 (+/-0.22). In linear regression analysis, the Apob/ApoA1 ratio was significantly associated with all the ultrasonic measurements of early atherosclerosis (intima media thickness, IMTcc, IMTmax, TPT and BPB). These findings remained significant after correcting for age, gender, smoking, hypertension and diabetes (P<0.001 for all). CONCLUSION: The results indicate that a high ApoB/ApoA1 ratio is associated not only with early atherosclerosis but also with hypoechoic (BPB) and by inference unstable plaques.

Snakes based segmentation of the common carotid artery intima media.

Ultrasound measurements of the human carotid artery walls are conventionally obtained by manually tracing interfaces between tissue layers. In this study we present a snakes segmentation technique for detecting the intima-media layer of the far wall of the common carotid artery (CCA) in longitudinal ultrasound images, by applying snakes, after normalization, speckle reduction, and normalization and speckle reduction. The proposed technique utilizes an improved snake initialization method, and an improved validation of the segmentation method. We have tested and clinically validated the segmentation technique on 100 longitudinal ultrasound images of the carotid artery based on manual measurements by two vascular experts, and a set of different evaluation criteria based on statistical measures and univariate statistical analysis. The results showed that there was no significant difference between all the snakes segmentation measurements and the manual measurements. For the normalized despeckled images, better snakes segmentation results with an intra-observer error of 0.08, a coefficient of variation of 12.5%, best Bland-Altman plot with smaller differences between experts (0.01, 0.09 for Expert1 and Expert 2, respectively), and a Hausdorff distance of 5.2, were obtained. Therefore, the pre-processing of ultrasound images of the carotid artery with normalization and speckle reduction, followed by the snakes segmentation algorithm can be used successfully in the measurement of IMT complementing the manual measurements. The present results are an expansion of data published earlier as an extended abstract in IFMBE Proceedings (Loizou et al. IEEE Int X Mediterr Conf Medicon Med Biol Eng POS-03 499:1-4, 2004).

Quality evaluation of ultrasound imaging in the carotid artery based on normalization and speckle reduction filtering.

Image quality is important when evaluating ultrasound images of the carotid for the assessment of the degree of atherosclerotic disease, or when transferring images through a telemedicine channel, and/or in other image processing tasks. The objective of this study was to investigate the usefulness of image quality evaluation based on image quality metrics and visual perception, in ultrasound imaging of the carotid artery after normalization and speckle reduction filtering. Image quality was evaluated based on statistical and texture features, image quality evaluation metrics, and visual perception evaluation made by two experts. These were computed on 80 longitudinal ultrasound images of the carotid bifurcation recorded from two different ultrasound scanners, the HDI ATL-3000 and the HDI ATL-5000 scanner, before (NF) and after (DS) speckle reduction filtering, after normalization (N), and after normalization and speckle reduction filtering (NDS). The results of this study showed that: (1) the normalized speckle reduction, NDS, images were rated visually better on both scanners; (2) the NDS images showed better statistical and texture analysis results on both scanners; (3) better image quality evaluation results were obtained between the original (NF) and normalized (N) images, i.e. NF-N, for both scanners, followed by the NF-DS images for the ATL HDI-5000 scanner and the NF-DS on the HDI ATL-3000 scanner; (4) the ATL HDI-5000 scanner images have considerable higher entropy than the ATL HDI-3000 scanner and thus more information content. However, based on the visual evaluation by the two experts, both scanners were rated similarly. The above findings are also in agreement with the visual perception evaluation, carried out by the two vascular experts. The results of this study showed that ultrasound image normalization and speckle reduction filtering are important preprocessing steps favoring image quality, and should be further investigated.

The role of common carotid artery end-diastolic velocity in near total or total internal carotid artery occlusion.

OBJECTIVES: To evaluate the role of the end-diastolic velocity (EDV) in the common carotid artery (CCA) as a marker of internal carotid artery (ICA) occlusion. DESIGN: Validation of retrospective data in a prospective clinical study. METHODS: The EDV in 94 patients with total ICA occlusion and in 24 patients with high grade (95-99%) unilateral ICA stenosis identified on extracranial carotid colour-flow Duplex imaging (CFDI) and arteriography was reviewed, and was retrospectively compared to the EDV of 176 normal individuals. Identification of patients with ICA occlusion was most accurate (99.3%) with an ipsilateral EDV > or = 12 cm/s and a DIFF > or = 10 cm/s (DIFF = contralateral EDV -- ipsilateral EDV). These values were then prospectively applied to all 886 patients (67 with high grade stenosis or occlusion) who underwent CFDI at our institution during 1994. RESULTS: The EDV > or = 12 had a 92% sensitivity, a 99.4% negative predictive value (NPV) and a 85% specificity in distinguishing between occluded and patent ICA's. In combination with a DIFF > or = 10 was 80.4% sensitive and 97.5% specific. The positive predictive value of the EDV > or = 12 in the distinction between 95-99% ICA stenosis and ICA occlusion was 78.3%, and that of the combination was 85.4%. The EDV was rarely zero and 10% of patients with normal or minimally diseased ICA's had an EDV > or = 12 and/or a DIFF > or = 10. CONCLUSIONS: The EDV < or = 12 cm/s is a sensitive marker of ICA occlusion with a high NPV and in combination with the DIFF > or = 10 cm/s, is specific. Nevertheless, EDV parameters are inaccurate in the distinction of 95-99% ICA stenosis from occlusion. Low EDV can be found in a number of patients with minor or no ICA disease, particularly in those with a stroke or silent cerebral infarct.