Stefan Rosfors

Relationship Between Intima-Media Thickness in the Common Carotid Artery and Atherosclerosis in the Carotid Bifurcation

BACKGROUND AND PURPOSE An increase in intima-media thickness (IMT) in the common carotid artery (CCA) is commonly used as a marker of atherosclerosis. The purpose of this study was to investigate the relationship between IMT in the CCA and atherosclerosis in the carotid bifurcation. METHODS 182 consecutive patients (mean age, 67 years) referred for carotid duplex scanning were included. We measured IMT and classified plaques by means of a high-resolution ultrasound technique. RESULTS IMT was correlated to age, male gender, ischemic heart disease, and presence of plaques or stenoses in any of the carotid bifurcations. In men, IMT was larger on the left than on the right side. Plaques were seen in 163 carotid bifurcations, in 45 of these with > 50% stenosis. On the left side but not on the right, there was a correlation between IMT in the CCA and presence of plaques or stenoses in the carotid bifurcation. Echogenic plaques were more common than echolucent, but the latter caused significantly more stenoses. No relationship was found between plaque echogenicity and IMT. CONCLUSIONS IMT of the CCA is correlated to the degree of atherosclerosis in the carotid bifurcations in general and on the left side also to the presence of plaques or stenoses in the left carotid bifurcation. Our results support earlier observations suggesting faster development of carotid atherosclerosis on the left than on the right side. Echogenic plaques were more common and generally smaller than echolucent plaques, but there was no correlation between plaque echogenicity and IMT.

Prolonged thromboprophylaxis with dalteparin after surgical treatment of achilles tendon rupture: a randomized, placebo-controlled study.

Objectives: Prophylaxis against thromboembolic complications has become routine after major orthopedic surgery. In contrast, it remains an issue for debate whether prophylaxis after minor surgery and immobilization is necessary, even though these treatments are well-known risk factors for deep-vein thrombosis (DVT). The objective of this study was to evaluate the efficacy of dalteparin during lower-limb immobilization after surgical treatment of Achilles tendon rupture. Design Setting, and Patients: Randomized, placebo-controlled, double-blind study of 105 consecutive patients surgically treated for Achilles tendon rupture in a trauma hospital. DVT screening with color duplex sonography was conducted 3 weeks and 6 weeks after surgery. All DVTs were confirmed with phlebography. Intervention was placebo or dalteparin (5000 U) given subcutaneously once daily for 6 weeks postoperatively. Main Outcome Measure: DVT incidence. Results: Primary endpoint analysis was available for 91 patients. DVT was diagnosed in 16 of 47 patients (34%) in the dalteparin group and in 16 of 44 patients (36%) in the placebo group. These figures are not significantly different (P = 0.8). Proximal DVT was diagnosed in 1 patient (2%) in the dalteparin group and in 3 patients (6%) in the placebo group (P = 0.6). No pulmonary emboli or major bleeding occurred in either of the groups. Conclusions: DVT is common after surgical treatment of Achilles tendon rupture, and therefore effective thromboprophylaxis is desirable. In our study, thromboprophylaxis with dalteparin, however, does not affect the incidence of DVT during immobilization after Achilles tendon rupture surgery. Long-term effects of immobilization, such as the risk for postthrombotic syndrome, need to be investigated further.

Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery A randomized placebo-controlled, double-blind study

Background Skeletal trauma and immobilization are well-known risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE). While prophylaxis against thromboembolic complications has become routine after major orthopedic surgery, whether or not prophylaxis after minor surgery and lower limb immobilization is necessary is still under debate. Methods In a double-blind, placebo-controlled study, 272 consecutive patients were randomized to receive either thromboprophylaxis with Dalteparin (n = 136) or placebo (n = 136) for 5 weeks after ankle fracture surgery. All patients received 1 week of initial treatment with Dalteparin before randomization. A unilateral phlebography was performed when the cast was removed. Results The overall incidence of DVT was 21% (95% CI: 13–29%) in the Dalteparin group and 28% (CI: 19– 37%) in the placebo group (risk ratio = 0.8, CI: 0.6–1.1; p = 0.3). The incidence of proximal DVTs was 4% and 3%, respectively. No major bleeding occurred. Interpretation We found no significant difference in the incidence of DVT between the 2 treatment groups and our results do not support prolonged thromboprophylaxis. The overall incidence of DVT was high, reflecting the potential risk of PE and post-thrombotic syndrome after ankle fracture surgery. Most of the DVTs were asymptomatic, however, and were located in distal veins.

Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research.

High sensitivity with color duplex sonography in thrombosis screening after ankle fracture surgery

Summary.  Background: Phlebography is regarded as the reference standard for diagnosing asymptomatic deep vein thrombosis (DVT) in studies of thromboprophylaxis. However, technical advances with noninvasive color duplex sonography (CDS) have made this procedure an interesting alternative. Objectives: The objective of the present prospective study was to compare the sensitivity and specificity of CDS with those of phlebography. Patients: The first 180 consecutive patients included in a larger randomized trial for prolonged thromboprophylaxis were subject to unilateral CDS and to phlebography after ankle fracture surgery. The patients were examined 6 weeks after surgery, all examinations being evaluated blindly. After patient drop outs and exclusions, 144 patients were left for analysis. Results: Phlebography and CDS examinations were inconclusive or were not completed for 19% of these patients (28/144). DVT was diagnosed by phlebography in 21% (24/116) of the remaining patients. Most of the thrombi were isolated calf DVTs (18/24). In contrast, DVT was diagnosed by CDS in 31% of these patients (36/116): only one case diagnosed by phlebography was missed by CDS. The specificity of CDS is thus 86% and its sensitivity is 96%. The positive predictive value is 64%, and the negative predictive value is 99%. Conclusions: CDS is a safe method for detecting asymptomatic distal DVT. It has a high sensitivity and high negative predictive value, which means that the method is highly reliable to rule out DVT. Our results indicate that CDS could be considered as an alternative method for DVT screening.

Duplex ultrasound in patients with suspected aorto-iliac occlusive disease

Duplex ultrasound scanning was used to localise and classify aorto-iliac occlusive disease. The study included 76 consecutive examinations of 73 patients with signs suggestive of proximal occlusive disease either by history or from traditional non-invasive laboratory investigation. Duplex ultrasound scanning indicated the presence of significant proximal occlusive disease in 70/101 limbs with suspected aorto-iliac disease. In total, 383/393 proximal arterial segments were assessed. A complete evaluation of the aorto-iliac region was possible in 91% of the patients. Duplex scanning was superior to oscillometric amplitude measurements and to CW Doppler examination, especially in patients with concomitant disease of the proximal superficial and deep femoral arteries. Duplex classification of stenoses correlated well with angiographic results obtained in 60 limbs with exact agreement in 194/211 (92%) arterial segments. Three of the patients with disparity between ultrasonography and angiography were investigated with intraarterial pressure measurements demonstrating that these lesions were underestimated by angiography. We conclude that Duplex ultrasound is feasible and accurate in detecting and grading lesions in the aorto-iliac region. This method provides important clinically useful haemodynamic information non-invasively in patients with suspected aorto-iliac occlusive disease.

Carotid atherosclerosis is correlated with extent and severity of coronary artery disease evaluated by myocardial perfusion scintigraphy.

Increased intima-media thickness (IMT) in the common carotid artery (CCA) correlates with conventional risk factors for cardiovascular disease and is an independent predictor of cardiac events. However, correlation between IMT and degree of ischemic heart disease evaluated by coronary angiogram is weak. The purpose of this study was to investigate the relationship between measures of carotid atherosclerosis and the extent and severity of coronary artery disease (CAD) in 111 consecutive patients (60 men and 51 women, mean age 60 years) with known or suspected CAD who were investigated with adenosine-stress myocardial perfusion scintigraphy. Common carotid artery lumen diameter (LD) and IMT of the carotid bulb and distal CCA were measured with ultrasound, and CCA cross-sectional intima-media area (CIMA) was calculated. Seventy-two of 110 patients (65%) had significant perfusion defects. Increasing carotid plaque occurrence (absence, unilateral or bilateral occurrence) correlated with more advanced CAD (p<0.01). The extent and severity of myocardial hypoperfusion correlated significantly with presence of carotid plaque (r =0.23 and 0.24 respectively, p<0.05), CIMA (r =0.23 and 0.22, p<0.05), and LD (r =0.26 and 0.25, p<0.01) but not with IMT. In contrast to CIMA, LD failed to show an independent relation to extent of CAD after adjustment for age, sex, and body mass index. In conclusion, in subjects with intermediate to high risk of ischemic heart disease, occurrence of carotid plaques and increased cross-sectional intima-media area in the common carotid artery are the best parameters for predicting CAD expressed as myocardial hypoperfusion.

Effects of exercise on Doppler-derived pressure difference, valve resistance, and effective orifice area in different aortic valve prostheses of similar size

The effects of increased transvalvular volume flow on Doppler-derived measurements were compared in similarly sized, normally functioning, mechanical prostheses, stented and stentless porcine bioprostheses, and homografts. Homograft and stentless valves showed the largest effective orifice area and the lowest pressure differences and valve resistance at rest and during exercise-induced increase in flow rates.

Early signs of atherosclerosis are associated with insulin resistance in non-obese adolescent and young adults with type 1 diabetes

BackgroundPatients with type 1 diabetes have a substantial risk of developing cardiovascular complications early in life. We aimed to explore the role of insulin sensitivity (Si) as an early factor of atherosclerosis in young type 1 diabetes vs. non-diabetic subjects.MethodsForty adolescent and young adult individuals (20 type 1 diabetics and 20 non-diabetics), age 14–20 years, without characteristics of the metabolic syndrome, participated in this cross-sectional study. After an overnight fast, Si was measured by hyperinsulinemic euglycemic clamp (40 mU/m2) and calculated by glucose infusion rate (GIR). Carotid intima-media thickness (cIMT) was measured in the common carotid artery with high-resolution ultrasonography. Risk factors of atherosclerosis (Body mass index [BMI], waist circumference, systolic blood pressure [sBP], triglycerides, low HDL-cholesterol and HbA1c) were also investigated.ResultscIMT was increased (0.52 ± 0.1 vs. 0.47 ± 0.1 mm, P < 0.01), whereas GIR was decreased (5.0 ± 2.1 vs. 7.1 ± 2.2 mg/kg/min, P < 0.01) in type 1 diabetics vs. non-diabetics. The differences in cIMT were negatively associated with Si (r = −0.4, P < 0.01) and positively associated with waist circumference (r = 0.34, P = 0.03), with no such associations between BMI (r = 0.15, P = 0.32), sBP (r = 0.09, P = 0.58), triglycerides (r = 0.07, P = 0.66), HDL-cholesterol (r = 0.10, P = 0.55) and HbA1c (r = 0.24, P = 0.13). In a multivariate regression model, between cIMT (dependent) and group (explanatory), only adjustment for Si affected the significance (ß = 0.08, P = 0.11) vs. (ß = 0.07, P < 0.01) for the whole model. No interaction between cIMT, groups and Si was observed.ConclusionscIMT is increased and associated with insulin resistance in adolescent, non-obese type 1 diabetic subjects. Although, no conclusions toward a causal relationship can be drawn from current findings, insulin resistance emerges as an important factor reflecting early signs of atherosclerosis in this small cohort.

Venous photoplethysmography: Relationship between transducer position and regional distribution of venous insufficiency

This study was performed to evaluate the photoplethysmographic technique in venous disease, especially regarding the effect of different positions of the photoplethysmographic transducer and the possibility of measuring regional changes in venous circulation. For this purpose photoplethysmographic recovery times were assessed from three different parts of the lower leg, that is, anterior midcalf level, medial midcalf level, and medial malleolar level. In patients with documented venous disease, regional photoplethysmographic findings were compared with results from venous pressure measurements, ascending/descending phlebography, foot volumetry, venous plethysmography, and Doppler investigation of the anterior tibial veins. The best correlation with pressure and volume recordings at the foot was obtained at the medial malleolar level. Only photoplethysmographic recovery times recorded at the anterior aspect of the leg were influenced by reflux in the anterior tibial veins. The present results indicate that photoplethysmographic recovery times reflect regional venous hemodynamics rather than overall venous hemodynamics in the limb. Photoplethysmographic recovery times were also found to be more related to superficial than to deep venous insufficiency. The results might have clinical implications when evaluating patients with regional venous dysfunction and in follow-up studies after venous surgery.