Hemodynamic and morphologic evaluation of sequelae of primary upper extremity deep venous thromboses treated with anticoagulation

ObjectivesThis study was performed to describe venous function, residual morphologic abnormalities, and the occurrence of post-thrombotic syndrome in patients with conservatively treated primary upper-extremity deep venous thromboses (UEDVT).MethodThis was a retrospective follow-up study of 31 patients with previous primary UEDVT treated with anticoagulation only, identified by a search of medical records. The mean follow-up time was 5 years. The patients were evaluated by interview, clinical examination, computerized strain-gauge plethysmography, and color duplex ultrasound imaging. The grade of post-thrombotic syndrome was rated according to the Villalta score (0 to 3 on each of four subjective and five clinically assessed features).ResultsThe rate of venous emptying was significantly lower in the arms with DVTs than in the contralateral arms (P < .001). Eleven of the patients (35%) had a remaining outflow obstruction in the affected arm (venous emptying <68 mL/100 mL per min). Eighteen (58%) had a residual thrombus according to color duplex ultrasound scans, with four remaining occluded subclavian veins. None of the patients had deep or superficial venous reflux. There was no statistically significant relationship between plethysmographic and duplex findings. Most (77%) of the patients reported remaining symptoms in the affected arm, and there was a significant side difference in upper arm circumference (P < .001). Approximately one third had developed a moderate grade of post-thrombotic syndrome according to the Villalta score (total, 5 to 9). No significant relation was evident between the post-thrombotic syndrome score and duplex findings. Patients with post-thrombotic syndrome had a lower venous emptying value than those without (69 vs 84 mL/100 mL per min), but this difference was not statistically significant.ConclusionsPatients with conservatively treated previous primary UEDVT had significantly reduced venous outflow capacity and a residual thrombus was common. Swelling of the arm was the most common symptom, and one third had a moderate grade of post-thrombotic syndrome. However, there was no clear relation between hemodynamic and morphologic factors and the development of post-thrombotic syndrome in these 31 patients, examined at a mean of 5 years after an acute DVT episode

A follow-up study of the fate of small asymptomatic deep venous thromboses

<p>Abstract</p> <p>Background</p> <p>Postoperative asymptomatic deep venous thromboses (ADVT) can give rise to posttthrombotic syndrome (PTS), but there are still many unresolved issues in this context. For example, there is a lack of knowledge regarding the fate of small ADVT following minor orthopedic surgery. This follow-up study evaluates postthrombotic changes and clinical manifestations of PTS in a group of patients with asymptomatic calf vein DVT after surgery for Achilles tendon rupture.</p> <p>Methods</p> <p>Forty-six consecutive patients with distal ADVT were contacted and enrolled in a follow-up consisting of a single visit at the hospital at a mean time of 5 years postoperatively, including clinical examination and scoring, ultrasonography and venous plethysmography. All patients had participated in DVT-screening with colour duplex ultrasound (CDU) 3 and 6 weeks postoperatively and 80% of them were treated with anticoagulation.</p> <p>Results</p> <p>With CDU postthrombotic changes and deep venous reflux were detected at follow-up in more than 50% of the patients, more commonly in somewhat larger calf DVT:s initially affecting more than one vessel. However, only about 10% of the patients had significant venous reflux according to venous plethysmography. No patient had plethysmographic evidence of remaining outflow obstruction, but presence of postthrombotic changes shown with CDU negatively influenced venous outflow capacity measured with plethysmography. A clinical entity of PTS was rarely found and occurred only in two patients (4%) and then classified by Villalta scoring as of mild degree with few clinical signs of disease. Distal ADVT:s detected in the early postoperative period (3 weeks) showed DVT-progression in 75% of the limbs that were still immobilized and without anticoagulation.</p> <p>Conclusions</p> <p>Asymptomatic postoperative distal DVT:s following surgery for Achilles tendon rupture have a good prognosis and a favourable clinical outcome. In our material of 46 patients the general appearance of the clinical entity of PTS at 5 years follow-up was low (<5%). Morphological and functional abnormalities were mainly seen in those patients that initially had somewhat larger distal DVT:s involving more than one deep calf vein segment.</p

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

Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age

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

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

<p>Abstract</p> <p>Background</p> <p>Patients with type 1 diabetes have a substantial risk of developing cardiovascular complications early in life. We aimed to explore the role of insulin sensitivity (S_i) as an early factor of atherosclerosis in young type 1 diabetes <it>vs.</it> non-diabetic subjects.</p> <p>Methods</p> <p>Forty 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, S_i 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 HbA_1c) were also investigated.</p> <p>Results</p> <p>cIMT was increased (0.52 ± 0.1 <it>vs.</it> 0.47 ± 0.1 mm, <it>P</it> < 0.01), whereas GIR was decreased (5.0 ± 2.1 <it>vs.</it> 7.1 ± 2.2 mg/kg/min, <it>P</it> < 0.01) in type 1 diabetics <it>vs.</it> non-diabetics. The differences in cIMT were negatively associated with S_i (<it>r</it> = −0.4, <it>P</it> < 0.01) and positively associated with waist circumference (<it>r</it> = 0.34, <it>P</it> = 0.03), with no such associations between BMI (<it>r</it> = 0.15, <it>P</it> = 0.32), sBP (<it>r</it> = 0.09, <it>P</it> = 0.58), triglycerides (<it>r</it> = 0.07, <it>P</it> = 0.66), HDL-cholesterol (<it>r</it> = 0.10, <it>P</it> = 0.55) and HbA_1c (<it>r</it> = 0.24, <it>P</it> = 0.13). In a multivariate regression model, between cIMT (dependent) and group (explanatory), only adjustment for S_i affected the significance (ß = 0.08, <it>P</it> = 0.11) <it>vs.</it> (ß = 0.07, <it>P</it> < 0.01) for the whole model. No interaction between cIMT, groups and S_i was observed.</p> <p>Conclusions</p> <p>cIMT 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.</p