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Blood coagulation is a complex physiological process critical for maintaining hemostasis, and disruptions in this system can lead to various health complications. Since the effects of specific food groups on a series of circulating coagulation parameters in the population are not well established, this study examines such associations in the population-based KORA-Fit study. A total of 595 subjects (263 men and 332 women) born between 1945 and 1964 and living in the study region of Augsburg were included in the study. Habitual food intake was estimated based on a combination of repeated 24-h food lists (24HFLs) and a food frequency questionnaire (FFQ). Antithrombin III, D-dimers, factor VIII, fibrinogen, protein C, protein S, aPTT, Quick value and INR were measured in citrate plasma. Multivariable linear regression models were applied to investigate associations between the consumption of specific foods of plant or animal origin and hemostatic factors. We found that the consumption of plant-based food groups, including green leafy vegetables (rich in vitamin K1), were hardly associated with coagulation parameters. Surprisingly, a high consumption of dairy products and especially butter were associated with higher D-dimer concentrations. These findings need further evaluation in prospective studies. [ABSTRACT FROM AUTHOR]

Abstract Background Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population. Methods After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status. Results In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients. Conclusion In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Background: Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population. Methods: After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status. Results: In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients. Conclusion: In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects. [ABSTRACT FROM AUTHOR]

Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018–2019, aged 54–74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects. [ABSTRACT FROM AUTHOR]

Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018–2019, aged 54–74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects.

Background: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis., Objectives: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment., Methods: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT., Results: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10 -11 . Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10 -10 ; rs1421067 (CHD9), P = 1.81 × 10 -14 ; and rs34780449, near ROBO1 gene, P = 1.64 × 10 -8 . Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10 -14 . Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05)., Conclusion: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA1 levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.

This is the era of component therapy. Therefore there is a need for rational use of platelet concentrate. Lot of knowledge has been added recently in the field of platelet specially about the platelet rich plasma and its application in clinical practice. The current review focuses on improvement in preparation of platelet rich plasma, the procedure to make the same more safe and its rational use. Furthermore newer aspects of platelet concentrate use in surgical practice and for regenerative medicine has also been discussed. It also covers some progress and hurdles in preparation of platelet substitutes.

Context: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. Aims: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. Settings and Design: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. Subjects and Methods: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. Statistical Analysis Used: One-way analysis of variance, Kruskal-Wallis, and post hoc Tukey honestly significant difference or Conover's nonparametric multiple comparison tests for comparison of the study groups. Results: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. Conclusions: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis. [ABSTRACT FROM AUTHOR]

Objective: Depression may be a risk factor for coronary heart disease (CHD) morbidity and mortality, but the mechanism(s) for the association are not established. The present study examined the relationship between one possible mechanism, hemostatic factors, and depressive symptoms in middle-aged women. Method: We measured levels of fibrinogen, Factor VIIc, plasminogen activator inhibitor antigen-1 (PAI-1), and tissue plasminogen activator antigen (TPA-ag) in 3,016 women aged 42-52 years enrolled in the Study of Women’s Health Across the Nation (SWAN). Depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale (CES-D), with scores > 16 suggestive of depression. Results: Depressed women had high levels of all four hemostatic factors ( all p

Objective: In this study, we evaluated hemostatic factors related to cardiovascular disease in postmenopausal women receiving estrogen or combined progestogen replacement therapy. We further compared the effects of natural and synthetic progestogens on lipid profiles and hemostatic factors. Materials and Methods: Of the 60 subjects, 20 who had undergone a hysterectomy used conjugated equine estrogen (CEE; 0.625 mg/day) alone (group I); the other 40 used CEE (0.625 mg/day for 21 days) plus either micronized progesterone (200 mg/day; group II; n = 20) or medroxyprogesterone acetate (10 mg/day; group III; n = 20) for the final 10 days. The effects on lipid profiles and hemostatic parameters were evaluated at baseline and after 6 and 12 months of treatment. Results: Only group I patients showed a significant reduction in low-density lipoprotein cholesterol (LDL-C) and the atherogenic ratios of total cholesterol/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C, as well as an increase in triglycerides. Tissue plasminogen activator levels decreased significantly in group I but did not change in groups II or III. Antithrombin III and protein S levels decreased significantly in group I but increased in groups II and III. Group I patients showed a stronger increase in protein C than those in either group II or III. There were no significant differences in hemostatic parameters between groups II and III. Conclusion: Estrogen replacement therapy may have beneficial effects on lipid profile and fibrinolytic factors in postmenopausal women. Both natural and synthetic progestogens attenuated the effects of estrogen. The 1-year effects of hormone replacement therapy on factors related to venous thromboembolism were positive. Micronized progesterone was not superior to medroxyprogesterone acetate.

BACKGROUND Our aim was to assess whether electrocardiographic left ventricular hypertrophy (ECG-LVH) is associated with a higher risk of cardiovascular disease (CVD) events, independent of 24-hour blood pressure (BP) and circulating levels of norepinephrine and hemostatic factors. METHODS In 514 older hypertensive patients (mean age 72.3 years; 37% men), we assessed ambulatory BP values, circulating levels of norepinephrine and hemostatic factors (plasma fibrinogen, prothrombin fragment 1+2 (F1+2), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1)), and the presence or absence of ECG-LVH (Sokolow–Lyon voltage ≥ 3.5 mV). The incidence of CVD events (i.e., myocardial infarction and stroke) was prospectively ascertained. RESULTS During an average 41 months of follow-up (1,751 person-years), 43 stroke and 3 myocardial infarction events occurred. At baseline, patients with ECG-LVH had higher mean 24-hour BP (148.8/83.8 mm Hg vs. 135.7/77.2 mm Hg) and circulating norepinephrine levels (404.6 pg/ml vs. 336.3 pg/ml) compared to those without ECG-LVH; the differences remained unchanged after adjustment for age, gender, smoking status, presence of diabetes, and antihypertensive medication uses at follow-up time (all P < 0.01). Cox proportional hazards models suggested that the hazard ratio (HR; 95% confidence interval (CI)) of CVD events for those with ECG-LVH was 4.4 (2.3–8.2), and the association between ECG-LVH and incident CVD events remained significant after adjustment for high 24-hour BP (≥130/80 mm Hg), nocturnal SBP, circulating norepinephrine and fibrinogen levels (HRs, 3.5–4.2, all P < 0.001). CONCLUSIONS In older hypertensive patients, ECG-LVH was associated with a higher risk of CVD events, independent of ambulatory BP parameters and circulating norepinephrine and fibrinogen levels. [ABSTRACT FROM AUTHOR]

Background and aims Obesity has been associated with increased levels of hemostatic factors. However, few studies have compared change in different anthropometric measures of adiposity in relation to change in levels of hemostatic factors. Our aim was to examine prospectively the association of change in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), and waist circumference-height ratio (WHtR) with change in markers of hemostasis in a population of postmenopausal women. Methods and results A subsample of women in the Women's Health Initiative (WHI) cohort had fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up. Of these, we studied the 2593 women who were not in the intervention arm of any WHI clinical trial. Their blood samples were used to measure plasma fibrinogen, factor VII antigen activity, and factor VII concentration at baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression analyses to examine the longitudinal association between change in anthropometric factors and change in hemostatic factors, adjusting for a wide range of potential confounding factors. In longitudinal analyses using repeated measures, change in BMI, WC, and WHtR were all positively associated with change in all 3 hemostatic factors. Change in anthropometric variables was most strongly associated with change in fibrinogen. Conclusions Our results suggest that an increase in adiposity over time is robustly associated with increased levels of hemostatic factors. Registration number of clinical trial: NCT00000611 . [ABSTRACT FROM AUTHOR]

Background and aim Short sleep duration and poor quality sleep are associated with coronary heart disease (CHD) mortality; however, the underlying pathophysiologic process remains unclear. Sleep apnea may confound the association because of its relationship with formation of thrombi, the vascular occlusive process in CHD. We tested whether sleep duration and quality were associated with prothrombotic biomarkers in adults with a low probability of apnea. Methods We included adults aged 35-64years recruited from the community and who had an apnea hypopnea index <15 after one night of screening (n=506). Sleep duration and maintenance were determined from 7days of wrist actigraphy; daytime sleepiness was estimated using the Epworth Sleepiness Scale. Factor VIII (FVIII), von Willebrand factor (vWF), thrombin antithrombin (TAT) complexes, and plasminogen activator inhibitor-1 (PAI-1) were measured in fasting blood. Results Sleep duration, maintenance, and daytime sleepiness were not associated with FVIII, vWf, or TAT. Sleep maintenance was modestly inversely associated with higher levels of log-transformed PAI-1 (β=-0.07, standard error (SE)=0.03 per 4.8%, p=0.04) following adjustment for demographic characteristics, cardiovascular risk factors, and body mass index (BMI). Conclusions Mild impairment in sleep was modestly associated with activation of coagulation; further study is needed to evaluate the role of fibrinolytic factors in sleep-mediated coronary thrombosis. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of progressive liver disease encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and, ultimately, cirrhosis. NAFLD is strongly associated with features of the metabolic syndrome including abdominal overweight/obesity, hypertension, atherogenic dyslipidemia, glucose intolerance, or type 2 diabetes. With the advent of increasingly sedentary lifestyles and changing dietary patterns, the prevalence of obesity and insulin resistance has increased and, with this, NAFLD has rapidly become the most common cause of chronic liver disease in many developed countries. Importantly, accumulating evidence indicates that NAFLD is strongly associated with a prothrombotic tendency, which may, at least in part, contribute to the increased risk of atherothrombotic events observed in these patients. NAFLD, especially in its necroinflammatory form (NASH), releases a variety of proinflammatory and prothrombotic mediators that play important roles in the development and progression of acute atherothrombotic complications. NAFLD also exacerbates systemic and hepatic insulin resistance and causes atherogenic dyslipidemia. The purpose of this review is to briefly discuss the epidemiology and diagnosis of NAFLD, to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and various disorders of coagulation and fibrinolysis and their implications for the development of atherothrombotic complications, and to discuss some of the treatment options that may influence both NAFLD and its related vascular complications. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the effects of low lipoprotein receptor deficiency in cholesterol blood concentrations, blood pressure, hemostatic factors, and the autonomic nervous system in three groups: control mice fed standard diet (CO, n=9), lipoprotein receptor-deficient mice (LDLr-/-, n=9) fed standard diet (LDLr-S) or hypercholesterolemic diet (LDLr-H, n=8). Frequency domain analysis of heart rate and blood pressure variability was performed with an autoregressive algorithm. The spectral components were expressed in absolute (s2 or mmHg2) and normalized units. Spontaneous baroreflex sensitivity (BRS) was estimated by alpha index, defined as square root ratio between low frequency power in blood pressure variability and heart rate variability. LDLr/- mice presented a significant increase in the cholesterol blood concentration (mean±SD; mg/dl; LDLr-S=202.01±34.38 and LDLr-H=530.7±75.17) compared to CO (79.2±13.6), p=0.001. The receptor deletion was associated with a heart rate variability reduction (p=0.013). The BRS was reduced (p<0.05) in LDLr-S and LDL-H (mean±SD: 0.96±0.39 and 0.59±0.34, respectively) compared to CO (4.02±1.92). Moreover, hypercholesterolemic diet significantly increased the cardiac sympathetic modulation (0V pattern of symbolic analysis: mean±SD, CO=8.04±4.53; LDLr-S=16.49±4.52 and LDLr-H=21.80±8.24, p=0.006). The 0V pattern was statically correlated to coagulation factor VII (r =0.555, p=0.0208). In LDLr-H, the concentration (interquartile range) of plasmatic fibrinogen and hemostatic factors VII (2.8–3.3) and XII (1.1–1.3) were increased compared to CO (0.9–1.1and 0.9–1.0, respectively) and LDLr-S (0.7–1.0 and 0.8–0.9, respectively) (p<0.004 for FVII and p<0.006 for FXII). Taken together, the results indicate that plasmatic cholesterol magnitude is determinant to increase the coagulation and the sympathetic modulation. [Copyright &y& Elsevier]

Objective: Although improved diagnostic tools and treatment approach, deep venous thrombosis is still an important cause of morbidity and mortality. Deep venous thrombosis is a common condition that affects more than 250 000 patients each year in the United States. In spite of limitations of the available diagnostic tools for detecting deep venous thrombosis, laboratory tests such as plasma D-dimer has been gained much interest recently. So, we aimed to investigate the D-dimer and all hemostatic factors in patients with deep vein thrombosis. Material and Methods: We investigated the levels of the D-dimer and Von Willebrand factor by enzyme linked immunosorbent assay (ELISA) in 120 patients with deep venous thrombosis and in 115 patients without deep venous thrombosis. We used standard methods for detecting the levels of the cholesterol, creatinin, INR, factor VIII: C ratio, and aPTT. We used Clauss method for detecting the fibrinogen levels. Results: We obtained important results in patients with deep venous thrombosis compared to in patients without deep vein thrombosis. Age, BMI, aPTT, INR, and total cholesterol levels were not found statistically differences in patients with deep venous thrombosis (p>0,05). Plasma D-dimer, creatinin, factor VII:C, and Von Willebrand factor levels were found higher in patients with deep venous thrombosis than in patients without deep venous thrombosis (respectively, p<0,001, p<0,01). But, plasma fibrinogen levels were not found lower in patients with deep venous thrombosis (p<0,01). Conclusion: In conclusion, we suggested that the plasma D-dimer and hemostatic factor levels may play an important role in diagnosis and treatment of deep venous thrombosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether elevated levels of hemostatic factors are associated with the subsequent development of subclinical cardiovascular disease. Methods: Fibrinogen, factors VII (FVII) and VIII (FVIII), and von Willebrand factor (vWF) were measured in 1396 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Coronary artery calcification (CAC) and carotid intimal/medial thickness (CIMT) were determined 13 years later. The adjusted prevalence of CAC and mean CIMT across the quartiles of each hemostatic factor was computed for the total sample and for each race and gender group. Results: The age-, race-, and gender-adjusted prevalences of CAC with increasing quartiles of fibrinogen were 14.4%, 15.2%, 20.0%, and 29.1% (p <0.001 for trend). This trend persisted after further adjustment for body mass index (BMI), smoking, educational level, center, systolic blood pressure (BP), diabetes, antihypertensive medication use, total and high-density lipoprotein (HDL) cholesterol, and CRP. A similar trend was observed for CIMT (age-, race- and gender-adjusted, p <0.001; multivariable-adjusted, p =0.014). Further analyses of race and gender subgroups showed that increasing quartiles of fibrinogen were associated with CAC and CIMT in all subgroups except black men. The prevalence of CAC was not associated with increasing quartiles of FVII, FVIII, or vWF, suggesting they may be less involved in plaque progression. Conclusion: An elevated fibrinogen concentration in persons aged 25–37 is independently associated with subclinical cardiovascular disease in the subsequent decade. [Copyright &y& Elsevier]

Abstract: Introduction: Dyslipidemia and thrombotic processes are both clearly involved in atherogenesis and its secondary complications. Moreover, inflammation has also been shown to play an important role in the pathophysiology of atherosclerosis. Our objective was to determine the association between inflammation, lipids and thrombosis in a group of patients with stable angina. Patients and methods: 295 patients (217 males and 78 females) with a mean age of 65.69±11.24years. Levels of C-reactive protein, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, lipoprotein(a), apolipoproteins A1 and B100, fibrinogen and D-dimer were determined for each. Results: Arithmetic and geometric means of C-reactive protein in the sample were 10.7 and 1.4mg/l, respectively. Distributing the sample by quartiles of C-reactive protein, we found a positive correlation between C-reactive protein, fibrinogen and D-dimer levels (p <0.000), and an inverse correlation for HDL cholesterol and apolipoprotein A1 (p <0.000). In multivariate analysis, fibrinogen (p <0.000) and D-dimer (p <0.01) levels were independently associated with high levels of C-reactive protein. Of the lipid factors, only apolipoprotein A1 (p <0.000) was independently and inversely associated with high levels of C-reactive protein. Conclusions: These data confirm the association between prothrombotic and inflammatory states and suggest the anti-inflammatory effect of apolipoprotein A1. [Copyright &y& Elsevier]

Objective : To study a possible use of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) as markers for changes in hemostatic factors during oral postmenopausal hormone replacement therapy (HRT). Methods : Twenty-eight postmenopausal women were treated with oral conjugated equine estrogens+oral medroxyprogesterone acetate (CEE+MPA, n=15) or with placebo (n=13). Serum SHBG, CBG, testosterone, cortisol and plasma coagulation factors, coagulation inhibitors and markers of coagulation activation were measured before and after 6 and 12 months of treatment. Results : Pretreatment plasminogen activator inhibitor 1 (PAI-1) levels correlated negatively to SHBG and antithrombin III (AT III) negatively to total and free cortisol. In the CEE+MPA group, CBG, SHBG and Factor VII increased, and PAI-1, AT III and free testosterone decreased during treatment. No significant changes were found in plasma von Willebrand factor antigen, thrombin-antithrombin complex, fibrin D-dimer and fibrinogen. A significant, negative correlation was found between changes in SHBG and PAI-1. No changes were found in the placebo group. Conclusion : The only correlation found between changes in "steroid sensitive" proteins and hemostatic factors was between increased SHBG and a possibly beneficial effect of estrogens, i.e. decreased PAI-1 values. SHBG or CBG could not be used as predictors of increased cardiovascular risk during postmenopausal oral HRT. [ABSTRACT FROM AUTHOR]

Background This study investigated the effects of comicronised fenofibrate in patients with dyslipidemia and polymetabolic syndrome X. Design After a 6-week dietary run-in phase, 37 male patients eligible on lipid criteria entered a 12-week treatment phase consisting of diet plus one capsule daily containing 200 mg of comicronised fenofibrate (Lipanthyl®). Results A significant reduction in plasma concentrations of total cholesterol, LDL cholesterol and triglyceride was observed after 4, 8 and 12 weeks of treatment with fenofibrate. The improvement in the atherogenic index LDL/HDL cholesterol from a pretreatment 3.8 to 3.0 after treatment was highly statistically significant and may be judged as satisfactory. Significant changes were also observed in haemostatic factors (fibrinogen reduced by 19%, factor VII activity reduced by 18%). Fasting serum insulin levels and insulin response (area under the curve) after oral glucose load were significantly reduced by 26.8% and 18.7%, respectively, indicating an improvement of insulin sensitivity. Systolic and diastolic blood pressure were significantly reduced. Uric acid was significantly reduced by 21.6%. Conclusion These favourable effects of comicronised fenofibrate both on lipid and non lipid parameters, including insulin sensitivity, may confer to this product a particular interest in the treatment of patients with polymetabolic syndrome X. [ABSTRACT FROM AUTHOR]

The following is a review of (largely) epidemiologic evidence on whether changes in plasma hemostatic concentrations occur with menopause and with postmenopausal hormone therapy which may have an impact on risk of ischemic heart disease. To date, only plasma fibrinogen has been positively associated with long-term risk of disease among women; however, data are sparse. Taken together, the evidence supports an impact of endogenous sex hormone levels on thrombotic potential and points to a modest increase in a number of plasma hemostatic factor levels at menopause. Results of studies of estrogen therapy are somewhat conflicting. Observational findings suggest that, except for possibly Factor VII level, estrogen therapy may prevent the menopause-related rise in plasma hemostatic factors. In contrast, controlled experiments have found increased markers of thrombin generation with use of common formulations of estrogen therapy. The hemostatic effects found with oral preparations do not appear to occur with transdermal forms of estrogen although data are limited. Overall, the evidence shows menopause to have an impact on plasma levels of hemostatic factors which appears to be modified by use of oral estrogen. Whether these alterations in plasma levels have an impact on risk of ischemic heart disease among postmenopausal women remains to be demonstrated. [ABSTRACT FROM AUTHOR]

The high incidence of cardiovascular morbidity and mortality in non-insulin-dependent diabetes mellitus with albuminuria cannot be fully explained by the presence of standard cardiovascular risk factors. We assessed some pathogenic factors of diabetic vascular atherosclerotic damage in 72 non-insulin-dependent diabetes mellitus patients controlled by diet alone and 60 healthy controls. Our study aim was to assess the early onset of these alterations and to correlate them with the presence of microalbuminuria. We determined their incidence in two carefully selected groups of diabetic patients without clinical signs of cardiovascular risk and complications, where diet alone achieved glycometabolic balance. Microalbuminuric patients had an alterated oxide-reductive balance and elevated values of plasminogen activator inhibitor, tissue plasminogen activator, von Willebrand factor, endothelin-1 and betathromboglobulin compared with the normoalbuminuric diabetics and controls. Our findings support the hypothesis that a state of endothelial dysfunction characterized by altered oxide-reductive balance, modified hemostasis and changes in the endothelial barrier properties occurs much earlier in non-insulin-dependent diabetic patient especially in diabetics with microalbuminuria. In addition, alterations in the oxide-reductive balance, and hemostasis occur early and may be an underlying cause of microangiopathic complications in microalbuminuric diabetics. [ABSTRACT FROM AUTHOR]

Abstract: Low-fat diet may play a role in prevention of cardiovascular disease (CVD) by altering the levels of hemostatic factors. There are yet limited data on the effects of low-fat diet on the circulating levels of these factors and existing studies are limited by small sample size and short duration of follow-up. We conducted an analysis in a subset of women (active arm = 723; control arm = 1036) within the Women’s Health Initiative Dietary Modification Trial to investigate the long term effect of a low-fat diet on circulating levels of fibrinogen, factor VII concentration and factor VII activity among postmenopausal women aged 50–79 years. Using linear mixed effects model with random intercept and data from three follow-up visits (years 1, 3 and 6) we evaluated the change in each factor over time. Overall, the changes in these factors were small (less than 5%) in both the arms of the trials at the end of intervention and there was no significant difference in mean change between the two arms. Our results indicate that the low-fat dietary intervention was not associated with significant changes in hemostatic factors among postmenopausal women. [Copyright &y& Elsevier]

The last half century of cancer research has seen an explosion in our understanding of the complex interplay between cancer cells and host-derived factors critical for cancer progression. Two important host-derived arms that are part of this complex interplay are the inflammatory immune compartment and the hemostatic system. Chronic pathological inflammation is a major factor in the development of multiple common malignancies, including adenocarcinomas of the colon, pancreas, prostate and breast. Hemostatic system components have also been shown to promote cancer progression in multiple contexts. What is only recently been recognized is the link between inflammation and hemostasis in cancer progression. The hemostatic and inflammatory innate immune systems co-evolved to deal with many of the same challenges, including trauma, infections, and thermal/chemical injuries. Their co-evolution necessarily led to bidirectional cross-talk whereby inflammatory cells can activate and alter hemostasis, and hemostatic system components serve as important regulators of inflammatory processes. This cross-talk is critical for the maintenance of vascular integrity, host defense, and wound healing. However, in the context of malignancy, the interplay of these integrated host systems has the capacity to promote multiple stages of malignancy, including tumorigenesis, tumor growth and metastatic dissemination. This review focuses on the interplay of inflammatory cells with the thrombin-fibrinogen axis and protease-activated receptor-1 in cancer pathobiology. Dissecting the mechanisms by which the inflammatory and hemostatic systems cooperatively promote cancer progression will fill in critical knowledge gaps in our understanding of malignancy, and also likely reveal novel therapeutic targets to treat and/or prevent cancer., Competing Interests: Conflict of interest statement J.S.P. receives research funding from Ionis Pharmaceuticals., (© 2020 Elsevier Ltd. All rights reserved.)