Assessment of Ventricular Repolarization in Sickle Cell Anemia Patients: The Role of QTc Interval, Tp-e Interval and Tp-e/QTc Ratio and Its Gender Implication.

BACKGROUND: Many specific and non-specific electrocardiographic abnormalities including ventricular arrhythmias have been reported in subjects with sickle cell anemia (SCA). In SCA patients, cardiac electrical abnormalities may be the leading cause of increased risk of arrhythmias. The corrected QT (QTc) interval, peak to the end of the T wave (Tp-e) interval and associated Tp-e/QTc ratio are promising measures of altered ventricular repolarization and increased arrhythmogenesis risk. AIM: This study assessed ventricular repolarization abnormalities in subjects with SCA using the QTc interval, Tp-e interval and Tp-e/QTc ratio, and also evaluated the gender differences in these parameters, as well as their determinants. METHODS: Sixty subjects with SCA and 60 healthy control subjects, matched for age and gender, were studied. All participants underwent physical examination, hematological and biochemical evaluation, and 12-lead electrocardiography (ECG) recording. QT and Tp-e intervals were measured from the ECG, and the QTc interval was calculated using Bazett's formula. Tp-e/QT and Tp-e/QTc ratios were also derived. RESULTS: QT and QTc intervals were prolonged in subjects with SCA. Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in male SCA subjects, with a paradoxical shortening in female SCA subjects. Plasminogen activator inhibitor-1 (PAI-1) was an independent determinant of QTc, while body mass index (BMI) was an independent determinant of both Tp-e interval and Tp-e/QTc ratio. CONCLUSION: Our results suggest an elevated risk for ventricular arrhythmogenesis in male SCA subjects. Furthermore, increased BMI and PAI-1 level are possible markers of ventricular repolarization abnormalities in SCA subjects.

Longitudinal assessment of D-dimer and plasminogen activator inhibitor type-1 plasma levels in pregnant women with risk factors for preeclampsia.

OBJECTIVE: Investigating D-Dimer/D-Di and plasminogen activator inhibitor type-1/PAI-1 levels throughout gestation in women with preeclampsia/PE risk factors. METHODS: D-Di and PAI-1 plasma levels were determined in 28 women at 12-19, 20-29, 30-34 and 35-40 weeks of gestation. RESULTS: D-Di was lower at 12-19 weeks and higher at 30-34 weeks in women who developed PE versus who did not develop it. D-Di increased throughout gestation in both groups, peaking earlier in pregnant women who developed PE versus who did not develop it. PA1-1 increased across gestation, but it didn't differ between groups. CONCLUSION: D-Di was able to discriminate these groups of women at 12-19 and 30-34 weeks of gestation.

Promoting Physical Activity and Exercise: JACC Health Promotion Series.

Physical inactivity is one of the leading modifiable risk factors for global mortality, with an estimated 20% to 30% increased risk of death compared with those who are physically active. The "behavior" of physical activity (PA) is multifactorial, including social, environmental, psychological, and genetic factors. Abundant scientific evidence has demonstrated that physically active people of all age groups and ethnicities have higher levels of cardiorespiratory fitness, health, and wellness, and a lower risk for developing several chronic medical illnesses, including cardiovascular disease, compared with those who are physically inactive. Although more intense and longer durations of PA correlate directly with improved outcomes, even small amounts of PA provide protective health benefits. In this state-of-the-art review, the authors focus on "healthy PA" with the emphasis on the pathophysiological effects of physical inactivity and PA on the cardiovascular system, mechanistic/triggering factors, the role of preventive actions through personal, education/environment, and societal/authoritative factors, as well as factors to provide guidance for caregivers of health promotion regarding PA. Sustainable and comprehensive programs to increase PA among all individuals need to be developed and implemented at local, regional, national, and international levels to effect positive changes and improve global health, especially the reduction of cardiovascular disease.

Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes.

OBJECTIVE: To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. RESEARCH DESIGN AND METHODS: Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). RESULTS: Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. CONCLUSIONS: Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up.

Stochastic sensors designed for assessment of biomarkers specific to obesity.

Two stochastic sensors based on the following oleamides: 1-adamantyloleamide and N,N-dimethyl-N-(2-oleylamidoethyl)amine physically immobilized on graphite paste were designed. The sensors were able to determine simultaneously from the whole blood of Wistar rats three biomarkers specific to obesity: leptin, interleukin-6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1). The whole blood samples were obtained from Wistar rats treated with oleoylethanolamide (OEA), (Z)-N-[(1S)-2-hidroxy-1-(phenylmethyl) ethyl]-9octadecenamide (OLA), and with the aqueous solution of 1% Tween 80 used as solvent for oleamides formulations (control samples). The proposed sensors were very sensitive and reliable for the assay of obesity biomarkers in whole blood of rats.

Childhood Socioeconomic Circumstances, Inflammation, and Hemostasis Among Midlife Women: Study of Women's Health Across the Nation.

BACKGROUND: Childhood socioeconomic status (SES) is related to risk for cardiovascular disease in adulthood, perhaps, in part, due to associations with inflammatory and hemostasis processes. We tested the hypotheses that childhood SES is related to C-reactive protein (CRP), fibrinogen, factor VIIc, and plasminogen activator inhibitor-1 (PAI-1) in midlife women and that the associations are mediated by adult SES and/or adult body mass index (BMI). METHODS: Using data from the prospective Study of Women's Health Across the Nation, we classified 1067 black and white women into 3 multidimensional childhood SES groups based on latent class analysis. Biological measures were assessed across 7 years along with covariates and mediators and analyzed by mixed regression models, followed by tests for mediation. RESULTS: Compared with women raised in high SES families, those from the lowest SES families had higher levels of CRP (b [standard error] = 0.37 [0.11]), PAI-1 (b = 0.23 [0.07]) factor VIIc (b = 0.05 [0.02]), and fibrinogen (b = 11.06 [4.89]), after adjustment for ethnicity, site, age, ratings of health between ages 11 and 18 years, visit, smoking status, menopausal status, stroke or heart attack, medications, and hormone use. Introduction of adult SES and BMI into the models reduced the childhood SES associations to nonsignificance for all four measures. Indirect mediation was apparent for adult education and BMI for CRP, and BMI for PAI-1. CONCLUSIONS: Women raised in lower SES families had elevated markers of inflammation and hemostasis, in part, due to elevated BMI and education in adulthood.

Selective pharmacological prophylaxis based on individual risk assessment using plasma levels of soluble fibrin and plasminogen-activator inhibitor-1 following total hip arthroplasty.

OBJECTIVES: The purpose of this prospective study was to evaluate the utility of preferential application of pharmacoprophylaxis based on the quantitative evaluation by soluble fibrin (SF) and plasminogen activator inhibitor-1 (PAI-1) analysis on the day after total hip arthroplasty (THA). METHODS: A hundred and sixteen patients were enrolled. High-risk patients were defined as those with elevated levels of SF or PAI-1, beyond their cut-off values, on the day after THA. For high-risk patients, fondaparinux was administered for 10 days postoperatively. When both plasma levels of SF and PAI-1 were less than their cutoff levels, the patients were regarded to be at low risk. For low-risk patients, only mechanical prophylaxis was applied. RESULTS: Sixty patients (52%) were considered to be at high risk. Among them, venous thromboembolism (VTE) was detected in five patients (8%) by CT angiography. In addition, there were four patients (3%) who developed bleeding complications. Fifty-six patients (48%) were considered to be at low risk, and only one patient (2%) developed VTE. CONCLUSION: The measurement of SF and PAI-1 levels on the day after surgery may be helpful to identify the individual risk for postoperative VTE. According to this evaluation, a half of patients might not need to administer anticoagulant agents following surgery.

Factors associated with early platelet activation in obese children.

OBJECTIVE: To investigate the factors associated with platelet activation in obese children. DESIGN: Cross-sectional study. SETTING: Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. PARTICIPANTS: 79 obese and 64 non-obese children between the ages of 5 and 10 years. MAIN OUTCOMES MEASURES: Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. RESULTS: Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (ß:0.381; t:4.665; P=0.0001), vWF (ß:0.211; t:2.926; P=0.004), UA (ß:0.166; t:2.146; P=0.034), and HDL (ß:-0.215; t:-2.819; P=0.006). CONCLUSIONS: Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults.

[Assessment of endothelial function in autoimmune diseases]. / Évaluation de la fonction endothéliale au cours des maladies auto-immunes.

Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases.

Effects of dietary composition on energy expenditure during weight-loss maintenance.

CONTEXT: Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied. OBJECTIVE: To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss. DESIGN, SETTING, AND PARTICIPANTS: A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings. INTERVENTION: After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks. MAIN OUTCOME MEASURES: Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components. RESULTS: Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged. CONCLUSION: Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00315354.

Prevalence of traditional and novel markers of cardiovascular disease risk in Scottish adolescents: socioeconomic effects.

Information on the health status and physical activity of Scottish adolescents is limited. This study examines the prevalence of cardiovascular disease (CVD) risk in Scottish adolescents by socioeconomic status (SES). Participants were recruited from two high schools that differed in the SES of the students in attendance. The sample included 73 boys and 34 girls (16.4 ± 0.6 years). Variables included anthropometry, physical activity, physical fitness, blood pressure, diet, and 11 metabolic markers of CVD risk. Significant sex differences (P ≤ 0.01) were noted for stature, waist circumference, waist-hip ratio, physical activity, cardiorespiratory fitness, muscular power, sprint speed, and several CVD risk factors: high-density lipoprotein (HDL), low-density lipoprotein (LDL), interleukin-6 (IL-6), and C-reactive protein (CRP) levels. Boys from a lower SES had significantly higher levels of glucose and plasminogen activator inhibitor-1 (PAI-1) but lower levels of adiponectin compared with boys from a higher SES. Girls from a lower SES had significantly (P ≤ 0.01) higher glucose and PAI-1 levels but lower levels of insulin and adiponectin than girls from a higher SES. High fat diets, low physical activity levels, and elevated CRP and total cholesterol levels were the CVD risk factors most commonly identified as being at-risk levels in this cohort, regardless of sex or SES. SES differences were not consistently apparent, but several CVD risk factors were identified as elevated in this sample of adolescents, regardless of sex or SES.

Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy.

OBJECTIVE: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). METHODS: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). RESULTS: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. CONCLUSIONS: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to a reduction in fibrinolytic activity.

Increased food intake and energy expenditure following administration of olanzapine to healthy men.

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12-day washout. Twenty-four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18-49 years) and 22.6 +/- 2.2 kg/m(2), respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor-I (PAI-I), leptin, and tumor necrosis factor-alpha (TNF-alpha) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short-term perturbations in IS.

Assessment of fibrinolytic activity by measuring the lysis time of a tissue-factor-induced clot: a feasibility evaluation.

A clot lysis time assay in which a tissue factor-induced fibrin clot is lysed by exogenously added tissue plasminogen activator has been recently reported. We evaluated the feasibility of clot lysis time in a routine hemostasis laboratory, and its correlation with thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels and changes with aging in 185 healthy participants. Clot lysis time was assessed by monitoring changes in turbidity during clot formation and subsequent lysis using a computerized kinetic spectrophotometric microtiter plate. After preliminary experiments, 100 and 160 ng/mL tissue plasminogen activator concentrations were chosen for the study. Clot lysis time was calculated by a new mathematical analysis of the lysis curve based on discrete derivative. Clot lysis time, thrombin activatable fibrinolysis inhibitor, and plasminogen activator inhibitor-1 plasma levels showed a normal distribution. For both concentrations of tissue plasminogen activator, clot lysis time progressively increased with increase in age (P < .0001) and was significantly correlated with thrombin activatable fibrinolysis inhibitor antigen, thrombin activatable fibrinolysis inhibitor activity, and plasminogen activator inhibitor-1 antigen (at least P < .01). During linear regression analysis, thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 antigen were found to significantly influence clot lysis time (at least P < .01). Clot lysis time determination has a good laboratory performance. Our new method of calculation is independent of the time of reading and allows a more accurate and consistent detection of both short and prolonged lysis times. Our data suggest the feasibility of the use of this test in the work of routine hemostasis laboratory.

Cardiometabolic risk among African American women: a pilot study.

OBJECTIVE: This study aimed to determine the associations of the Homeostatic Model of Assessment-insulin resistance (HOMA-ir), acanthosis nigricans, high-sensitivity C-reactive protein (hs-CRP), and plasminogen activator inhibitor-1 (PAI-1) with 2 of the commonly used definitions of metabolic syndrome (Adult Treatment Panel III [ATP III] and International Diabetes Federation [IDF]) among reproductive-age, healthy, free-living African American women. METHODS: A pilot study with a cross-sectional design examined 33 African American women aged 20 to 46 years (mean [SD], 31.24 [7.25] years) for the presence of metabolic syndrome determined by ATP III and IDF criteria, insulin resistance (HOMA-ir and/or acanthosis nigricans), degree of inflammation (hs-CRP), and presence of dysfibrinolysis (PAI-1). RESULTS: HOMA-ir identified insulin resistance in 27 (81.8%) women, whereas the presence of acanthosis nigricans indicated that 16 (48%) of these women manifested insulin resistance. Metabolic syndrome was found in 7 women (21.2%) by ATP III or in 9 (27.3%) women by IDF criteria. Bivariate correlations showed associations between HOMA-ir and waist circumference, body mass index (BMI), acanthosis nigricans, and the ATP III and IDF definitions for metabolic syndrome. Plasminogen activator inhibitor-1 was significantly correlated with waist circumference, BMI, fasting glucose, HOMA-ir, and ATP III. Both HOMA-ir and PAI-1 were significantly and negatively correlated with high-density lipoprotein cholesterol. High-sensitivity CRP was significantly correlated with BMI and 2-hour postglucose. CONCLUSION: Both dysfibrinolysis (PAI-1 levels) and insulin resistance (HOMA-ir), when individually regressed on the ATP III definition of metabolic syndrome, explained 32% and 29% of the respective variance. The addition of HOMA-ir measurement may significantly improve early recognition of cardiometabolic risk among reproductive-age African American women who have not yet met the criteria for the ATP III or IDF definitions of metabolic syndrome. Likewise, acanthosis nigricans is potentially a clinically significant screening tool when used to determine early recognition of insulin resistance and/or cardiometabolic risk among this population. African American women's risk for cardiovascular disease is likely underestimated based on the sole use of ATP III criteria for diagnosis of metabolic syndrome. Clinicians should consider a broader definition of risk than that contained within ATP III. Inclusion of biomarkers of inflammation and dysfibrinolysis, along with measures of insulin resistance, may add to early detection of cardiometabolic risk and ultimate reduction in cardiovascular health disparities among African American women.

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.

[Value of coagulation function and fibrinolytic system assessment in patients with gestational diabetes mellitus].

OBJECTIVE: To study the clinical implications of changes of coagulation function and fibrinolytic system in patients with gestational diabetes mellitus (GDM). METHODS: Twenty non-pregnant women, 20 with normal pregnancy and 46 with GDM were enrolled in this study for examinations of platelet alpha-granule membrane protein (GMP-140), Von Willebrand factor (vWF), antithrombin III activity (AT-III), plasminogen activity (PLG), activity of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI). RESULTS: vWF, GMP-140, PLG, D-dimer, PAI were obviously elevated while t-PA was lower in GDM patients as compared with the measurement in non-pregnant women and women with normal pregnancy (P<0.01). AT-III and ProC measurement showed no significant differences between GDM patients and women of the other two groups. CONCLUSION: GDM patients may have elevated platelet activation and fibrinolyic activity as well as vascular endothelial injuries, and antenatal assessment of the coagulation function can be of value for prevention and treatment of GDM.

A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecular-weight heparins--enoxaparin, nadroparin and dalteparin. The ESCAPe-END study.

BACKGROUND: Comparative data for efficacy and safety between various low-molecular-weight heparins (LMWHs) in patients with unstable angina is not available. The present study was conducted to compare the efficacy, safety, cost-effectiveness and effects on plasminogen activator inhibitor-1 (PAI-1) levels of three LMWHs--enoxaparin, nadroparin and dalteparin. METHODS: The study was a prospective, randomized, comparative, open with blinded endpoints (PROBE design) assessment with a 30-day follow-up. The primary endpoint of efficacy was a composite of cardiovascular death, myocardial infarction, recurrent angina and need for intervention. Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio. Plasma PAI-1 levels were estimated by ELISA. RESULTS: A total of 150 patients were available for intention-to-treat analysis. There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups. The secondary endpoint of silent ischemia was also not significantly different. Adverse events were similar in the three groups. The PAI-1 levels were not significantly different in the three groups. The total cost of treatment in the three groups was similar. CONCLUSION: Any of the three LMWHs evaluated in this study were similar with respect to efficacy, safety, PAI-1 levels and cost-effectiveness.

The constitutive procoagulant and hypofibrinolytic state in patients with intermittent claudication due to infrainguinal disease significantly improves with percutaneous transluminal balloon angioplasty.

BACKGROUND: Patients with intermittent lower limb claudication (IC) exhibit a prothrombotic diathesis that is acutely exacerbated by exercise. This may occur because of ischemia/reperfusion injury within the leg muscles during walking and may contribute to the increased risk of thrombotic vascular events in this group of patients. This randomized study compared the effect of lower limb revascularization by percutaneous transluminal balloon angioplasty (PTA), supervised exercise, and best medical therapy (BMT) alone on this prothrombotic state. METHODS: Twenty-three patients (16 men and 7 women; median age, 67 years; range, 57-77 years) with IC due to infrainguinal disease were randomized to receive BMT alone (n = 7), BMT plus PTA (n = 9), or BMT plus supervised exercise (n = 7) as part of the Health Technology Assessment-funded EXercise vs Angioplasty in Claudication Trial (EXACT). Patients were assessed at baseline and at 3 and 6 months. Thrombin-antithrombin complex (TAT) was determined as a marker of thrombin generation, and plasminogen activator inhibitor (PAI) antigen was determined as a marker of fibrinolysis. Increased TAT indicates a procoagulant state, and increased PAI antigen indicates a hypofibrinolytic state. RESULTS: At 6 months, subjects randomized to BMT plus PTA demonstrated a significant improvement in ankle-brachial pressure index (P = .013) and maximal walking distance (P = .008), a significant decline in resting thrombin generation (median [interquartile range] TAT, 6.4 microg/L [2.7-13.5 microg/L] to 1.5 microg/L [0.3-2.9 microg/L]; P = .038), and an improvement in resting fibrinolysis (median [interquartile range] PAI-1, 10.0 ng/mL [1.0-20.5 ng/mL] to 1.0 ng/mL [1.0-14.8 ng/mL]; P = .043). There was no significant change in any of these parameters in patients randomized to BMT plus supervised exercise or to BMT alone. CONCLUSIONS: The addition of lower limb revascularization by PTA to BMT in patients with IC due to infra-inguinal disease results in a medium-term improvement in the resting procoagulant and hypofibrinolytic state. This may translate into a reduction in morbidity and mortality from thrombotic vascular events in this group of patients.

Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit.

We investigated the correlation between disseminated intravascular coagulation (DIC) score and hemostatic parameters and sepsis-related organ failure assessment (SOFA) score with clinical outcome of patients with DIC in an intensive care unit (ICU). The SOFA score was markedly elevated in patients with DIC relative to patients without DIC and significantly higher in non-survivors than in survivors. Abnormalities in almost all hemostatic parameters were significant in patients with DIC, but there was no significant difference in almost all hemostatic parameters between survivors and non-survivors. However, plasma antithrombin (AT) levels were significantly lower in non-survivors than in survivors. Soluble fibrin (SF) and tissue type plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex correlated significantly with the SOFA score, whereas AT levels correlated significantly and negatively with the SOFA score. We conclude that the SOFA score is useful for predicting outcome in DIC patients in the ICU, and that hemostatic parameters, especially plasma AT levels, are also useful markers for organ failure and clinical outcome.