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The importance of measurement of plasma fibrinogen level among patients with type- 2 diabetes mellitus.
Abdul Razak, MK, Sultan, AA
Diabetes & metabolic syndrome. 2019;(2):1151-1158
Abstract
BACKGROUND & AIM: Fibrinogen has been implicated as a cause of atherosclerosis and its complications in patients with type 2 DM. We aimed to measure the plasma fibrinogen level in type 2 diabetics and to correlate it with the duration, type of treatment, HbA1c, smoking, lipid profile, diabetic retinopathy, hypertension and ischemic heart disease in comparison to control. METHODS A case control single center study included 50 patients with type 2 DM between the ages of 35-85 y who were randomly selected from the medical units of Baghdad Teaching Hospital compared to 30 non-diabetics as a control. After taking verbal consents; plasma fibrinogen levels were estimated and correlated with aimed variables. Odds ratios with 95% CI were calculated and regression analysis was performed for correlations. P ≤ 0.05 was considered statistically significant. RESULTS There were statistically significant differences regarding total cholesterol, TG, and LDL between cases and control. Mean HbA1c of diabetics was 8.31 ± 1.75% (P < 0.001). Cases showed plasma fibrinogen of (4.01 ± 1.89 g/dL) compared to (2.79 ± 0.55 g/dL) of control (P < 0.001). ROC curve revealed that the AUC was (0.679 ± 0.06, 95%CI = 0.561-0.797, P < 0.008). The sensitivity and specificity of the test at cut off value of 3.05 g/dL were 0.62 and 0.567 respectively. There was a significant correlation between fibrinogen level and each of HbA1c (r = 0.497, P < 0.001) and TG (r = 0.359, P = 0.01). CONCLUSIONS HbA1c has a significant positive effect on plasma fibrinogen and it is important to measure plasma fibrinogen level in patients with type 2 DM.
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Ospemifene's effects on lipids and coagulation factors: a post hoc analysis of phase 2 and 3 clinical trial data.
Archer, DF, Altomare, C, Jiang, W, Cort, S
Menopause (New York, N.Y.). 2017;(10):1167-1174
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Abstract
OBJECTIVE To evaluate the effect of ospemifene 60 mg on the lipid and coagulation parameters of postmenopausal women using data from five phase 2 and 3 clinical trials. METHODS Data for lipids and coagulation factors for 2,166 postmenopausal women were pooled from five randomized, placebo-controlled studies. Lipid and coagulation parameters included in this analysis were total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, activated partial thromboplastin time (aPTT), fibrinogen, antithrombin antigen, protein C Ag, and protein S Ag free. RESULTS Mean percent changes in HDL and LDL were significantly greater with ospemifene versus placebo at month 3 (HDL: 4.4% vs 0.2%; LDL: -5.2% vs 2.4%), month 6 (HDL: 5.1% vs 1.5%; LDL: -6.7% vs 2.4%), and month 12 (HDL: 2.3% vs -1.9%; LDL: -7.0% vs -2.1%; P < 0.05, for all comparisons). Ospemifene significantly reduced total cholesterol at 6 months (-1.8% vs 1.6%; P = 0.0345 versus placebo), and changes in triglycerides with ospemifene were similar to placebo at all three time points. In subgroup analyses based on age, body mass index, and baseline triglyceride level, ospemifene increased HDL and decreased LDL, but had no significant effect on total cholesterol and triglycerides relative to placebo. Ospemifene significantly improved fibrinogen and protein C antigen levels relative to placebo at months 3 (-8.7% vs -0.8% and -2.7% vs 0.5%, respectively), 6 (-6.0% vs 6.7% and -3.6 vs 8.0%), and 12 (-8.7% vs 7.3% and -4.5% vs 6.6%; P < 0.01, for all). The levels of all coagulation factors remained within the normal range throughout the studies. CONCLUSION Ospemifene 60 mg does not have a detrimental effect on lipid and coagulation parameters of postmenopausal women with up to 12 months of use.
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Fibrinogen and the Severity of Coronary Atherosclerosis among Adults with and without Statin Treatment: Lipid as a mediator.
Zhang, Y, Zhu, CG, Guo, YL, Li, S, Xu, RX, Dong, Q, Li, JJ
Heart, lung & circulation. 2016;(6):558-67
Abstract
BACKGROUND It has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators. METHODS We enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio. Moreover, using mediation analysis, the relationship between fibrinogen and lipids with high GS was evaluated. RESULTS Fibrinogen was positively associated with GS after adjustment (β=0.100, p<0.001). We stratified our analyses by statin use status and found that subjects in the upper fibrinogen tertiles had higher levels of atherogenic lipid parameters irrespective of statin status (p<0.001, all). Significantly, we observed a synergistic effect of fibrinogen and concurrent elevated lipid index for high GS. The adjusted odds ratios were greater in participants who had high fibrinogen levels and also high lipid index compared to those with low lipid index [on statin: 1.725(1.258-2.364) vs. 1.261(0.962-1.652); not on statin: 2.197(1.450-3.328) vs. 1.166(0.417-3.258)]. Specifically, mediation analysis indicated that around 24% of the effect of fibrinogen on high GS was mediated by lipid index, which was attenuated to 13% by statin status. CONCLUSIONS The increased risk of fibrinogen on coronary atherosclerosis appeared to be enhanced by the high atherogenic lipid levels, which mediated around 24% of this effect.
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Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core.
Corban, MT, Hung, OY, Mekonnen, G, Eshtehardi, P, Eapen, DJ, Rasoul-Arzrumly, E, Al Kassem, H, Manocha, P, Ko, YA, Sperling, LS, et al
Circulation journal : official journal of the Japanese Circulation Society. 2016;(4):931-7
Abstract
BACKGROUND Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. METHODS AND RESULTS Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47-63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. CONCLUSIONS In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC.
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Effect of long term low-fat dietary intervention on change in hemostatic factors: results from the Women's Health Initiative.
Rajpathak, SN, Xue, X, Wassertheil-Smoller, S, Van Horn, L, Snetselaar, L, Martin, LW, Rohan, TE
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2012;(4):337-9
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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.
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Endothelial function, endothelin-1, and fibrinogen in young women using the vaginal contraceptive ring.
Torgrimson, BN, Meendering, JR, Miller, NP, Kaplan, PF, Minson, CT
Fertility and sterility. 2009;(2):441-7
Abstract
OBJECTIVE To assess the effects of the vaginal contraceptive ring cycle on indices of cardiovascular health and risk by studying healthy women during the active hormone phase compared with the ring-free phase of a standard 21/7-day cycle. DESIGN Observational prospective cohort; 4 weeks' duration. SETTING Department of Human Physiology, University of Oregon. PATIENT(S): Twenty healthy women. INTERVENTION(S): Endothelial function testing using standard flow-mediated vasodilation of the brachial artery and sublingual nitroglycerin administration. All participants underwent venous blood collection. MAIN OUTCOME MEASURE(S): Endothelium-dependent and endothelium-independent vasodilation of the brachial artery using Doppler ultrasound imaging. Baseline levels of high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, endothelin-1, and fibrinogen. RESULT(S): The active hormone phase of the vaginal ring cycle showed significantly higher vasodilation compared with the ring-free phase. The active hormone phase also showed increased fibrinogen levels compared with the ring-free phase. Low-density lipoprotein lipid levels also fluctuated and were significantly higher during the ring-free phase. CONCLUSION(S): Preliminary study observations of improved endothelial function and lowered low-density lipoprotein levels during the active hormone phase versus the ring-free phase suggest that the vaginal contraceptive ring has beneficial effects on vascular health in women.
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Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.
Hsia, CH, Shen, MC, Lin, JS, Wen, YK, Hwang, KL, Cham, TM, Yang, NC
Nutrition research (New York, N.Y.). 2009;(3):190-6
Abstract
Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.
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Associations of plasma fibrinogen and factor VII clotting activity with coronary heart disease and stroke: prospective cohort study from the screening phase of the Thrombosis Prevention Trial.
Rudnicka, AR, Mt-Isa, S, Meade, TW
Journal of thrombosis and haemostasis : JTH. 2006;(11):2405-10
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BACKGROUND As with 'conventional' risk factors such as cholesterol and smoking, there is a need for large, long-term prospective studies on hemostatic factors. OBJECTIVES To investigate the prospective relationship of fibrinogen and factor VII clotting activity (FVIIc) with risk of coronary heart disease (CHD) and stroke in a study with a large number of outcomes over a period of 15 years. PATIENTS/METHODS A cohort of 22 715 men aged 45-69 years was screened for participation in the Thrombosis Prevention Trial. Men were followed up for fatal and non-fatal CHD and stroke events. There were 1515 CHD events (933 CHD deaths) and 391 strokes (180 stroke deaths). Hazard ratios (HRs) and 95% confidence intervals are expressed per standardized increase in log fibrinogen and log FVIIc, adjusting for age, trial treatment group, conventional CHD risk factors and regression dilution bias. RESULTS Hazard ratios for fibrinogen were 1.52 (1.37-1.70) for all CHD events, and 1.36 (1.09-1.69) for all strokes. Exclusion of events within the first 10 years showed a persistent association between CHD and fibrinogen, with an adjusted HR of 1.93 (1.42-2.64). The HRs for FVIIc, adjusting for age and trial treatment, were 1.07 (1.01-1.12) for all CHD events and 1.07 (0.97-1.20) for all strokes, and the fully adjusted HRs were, respectively, 0.97 (0.84-1.05) and 1.07 (0.85-1.33). CONCLUSIONS The persisting association between fibrinogen and CHD beyond 10 years may imply a causal effect. There is a small effect of FVIIc on CHD, after adjustment for age and trial treatment, but no association independent of other risk factors.
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[Randomised clinical trial of an intensive intervention into life-styles of patients with hyperfibrinogenaemia in primary prevention of cardiovascular pathology in primary health care].
Rodríguez Cristóbal, JJ, Benavides Márquez, F, Villaverde Grote, C, Peña Sendra, E, Flor Serra, F, Travé Mercadé, P, ,
Atencion primaria. 2005;(5):260-4
Abstract
OBJECTIVES To study the effect of an intensive programme to modify life-style on levels of plasma fibrinogen in patients without cardiovascular pathology, with high fibrinogen and normal cholesterol levels. To analyse whether the effect on fibrinogen is independent, or otherwise, of the effect on lipids. DESIGN Randomised clinical trial with a control. SETTING 11 health districts in L'Hospitalet de Llobregat and Barcelona. PARTICIPANTS 436 patients will be included, 218 individuals between 35 and 75 years old in each group, and without cardiovascular pathology (ischaemic cardiopathy, cerebral vascular accident or peripheral arteriopathy), with hyperfibrinogenaemia (fibrinogen > 300 mg/dL) and with plasma control < 250 mg/dL. INTERVENTIONS One group of patients will receive an intensive intervention (in frequency and intensity of counselling and treatment) for life-style changes, i.e. stopping smoking, low-calorie diet in case of overweight or obesity, and physical exercise. The follow-up of the intervention group will be every 2 months. The control group will follow customary treatments. MEASUREMENTS Levels of plasma fibrinogen. In addition, other relevant events will be recorded over a 2-year monitoring period: modification of risk factors, changes in quality of life, cardiovascular events or death. DISCUSSION The introduction of an intensive primary prevention intervention (life-style changes) in patients with hyperfibrinogenaemia could be a more effective measure than the habitual intervention for reducing plasma fibrinogen figures. In addition, these measures could be translated into a reduction of cardiovascular risk and an improvement in the patient s quality of life.
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Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents.
Balagopal, P, George, D, Patton, N, Yarandi, H, Roberts, WL, Bayne, E, Gidding, S
The Journal of pediatrics. 2005;(3):342-8
Abstract
OBJECTIVES The primary goals were to understand the relationship among the inflammatory factors, C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen, and indices of obesity in normoglycemic, insulin-resistant adolescents and to investigate the impact of a lifestyle-only intervention on these nontraditional risk factors for cardiovascular disease (CVD). STUDY DESIGN Randomized controlled lifestyle-only intervention study in adolescents. Of the 21 adolescents studied, 15 obese subjects (body mass index [BMI] = 37.6 +/- 3.3 kg/m 2 ) were randomized to either a lifestyle intervention program or usual care. The lean controls were studied only at baseline. Analysis of variance (ANOVA) for repeated measures was used to study intervention effect and t test, one-way ANOVA, and discriminant function analysis for baseline comparisons. RESULTS The intervention group maintained weight, whereas the control group gained weight (P = .02). A redistribution of body composition and a decrease in insulin resistance were observed. Elevated circulating concentrations of CRP, fibrinogen, and IL-6 were significantly reduced (all P CONCLUSIONS Modest lifestyle-only change in previously sedentary obese adolescents redistributes the parameters of body composition in the absence of weight loss and reverses, at least in part, the inflammatory state in association with an improvement of insulin resistance.