Association between obesity and a prothrombotic state: the Framingham Offspring Study

2004 ◽  
Vol 91 (04) ◽  
pp. 683-689 ◽  
Author(s):  
Guido Rosito ◽  
Ralph D’Agostino ◽  
Joseph Massaro ◽  
Izabella Lipinska ◽  
Murray Mittleman ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Plasminogen Activator ◽  
Body Mass ◽  
Plasma Viscosity ◽  
Factor Vii ◽  
Prothrombotic State ◽  
Waist To Hip Ratio ◽  
Hemostatic Factors ◽  
Pai 1

SummaryAlthough obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p<0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.

scholarly journals Risk factors mediating the effect of body-mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis

2020 ◽  
Author(s):  
Dipender Gill ◽  
Verena Zuber ◽  
Jesse Dawson ◽  
Jonathan Pearson-Stuttard ◽  
Alice R Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
European Ancestry ◽  
Standard Deviation Increase ◽  
Waist To Hip Ratio ◽  
Increased Risk ◽  
Artery Disease

Background: Higher body-mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits and smoking is not fully understood. Methods: Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, MR mediation analysis was performed to investigate the degree to which genetically predicted systolic blood pressure (SBP), diabetes, lipid traits and smoking mediated an effect of genetically predicted BMI and WHR on risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. Results: The 49% (95% confidence interval [CI] 39%-60%) increased risk of CAD conferred per 1-standard deviation increase in genetically predicted BMI attenuated to 34% (95% CI 24%-45%) after adjusting for genetically predicted SBP, to 27% (95% CI 17%-37%) after adjusting for genetically predicted diabetes, to 47% (95% CI 36%-59%) after adjusting for genetically predicted lipids, and to 46% (95% CI 34%-58%) after adjusting for genetically predicted smoking. Adjusting for all the mediators together, the increased risk attenuated to 14% (95% CI 4%-26%). A similar pattern of attenuation was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcomes. Conclusions: Measures to reduce obesity will lower risk of cardiovascular disease primarily by impacting on downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

Body fat percentage, body mass index and waist-to-hip ratio as predictors of mortality and cardiovascular disease

Heart ◽  
2014 ◽  
Vol 100 (20) ◽  
pp. 1613-1619 ◽  
Author(s):  
Phyo Kyaw Myint ◽  
Chun Shing Kwok ◽  
Robert N Luben ◽  
Nicholas J Wareham ◽  
Kay-Tee Khaw
Keyword(s):  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
Body Fat ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Waist To Hip Ratio ◽  
Predictors Of Mortality

Antigens of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor 1: Correlates in Nonsmoking Japanese and Caucasian Men and Women

1993 ◽  
Vol 70 (03) ◽  
pp. 475-480 ◽  
Author(s):  
Hiroyasu Iso ◽  
Aaron R Folsom ◽  
Kazuko A Koike ◽  
Shinichi Sato ◽  
Kenneth K Wu ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Body Mass ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Race Difference ◽  
Tissue Plasminogen ◽  
Caucasian Men ◽  
Pai 1

SummaryWe reported in a 1987 preliminary study that tissue plasminogen activator antigen was significantly higher in American Caucasian men than in Japanese men. To further examine possible differences in fibrinolytic activity between the two races, an expanded study was conducted in a total of 300 nonsmoking men and women aged 47-69 years in two population-based samples: rural Japanese living in Akita and Caucasians living in Minneapolis-St. Paul, MN. Antigens of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were measured. Mean t-PA antigen was 2.3 ng/ml higher in Caucasian men than in Japanese men (P <0.001), but no race difference was seen for women (P = 0.59). Mean PAI-1 was higher in Caucasians than in Japanese for both sexes, and the race difference in mean was 1.8 ng/ml for men (P = 0.07) and 4.4 ng/ml for women (P <0.001). Both t-PA and PAI-1 were associated positively with body mass index and blood triglycerides for all sex-race groups, and positively with alcohol intake for Japanese and Caucasian men. Compared to Japanese, Caucasians of both sexes had higher levels of body mass index and blood triglycerides, and lower average intake of alcohol among men. Even when adjusted for body mass index, triglycerides, alcohol and other cardiovascular risk factors, the race difference in mean t-PA antigen persisted for men (P <0.001), as did the difference in mean PAI-1 for men (P = 0.03) and women (P = 0.001). If PAI-1 is a risk factor for coronary heart disease, a higher level in Caucasians than Japanese would correspond to the higher mortality rate from coronary heart disease in the United States than in Japan.

scholarly journals Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis

2021 ◽  
Author(s):  
Dipender Gill ◽  
Verena Zuber ◽  
Jesse Dawson ◽  
Jonathan Pearson-Stuttard ◽  
Alice R. Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Standard Deviation Increase ◽  
Waist To Hip Ratio ◽  
Artery Disease

Abstract Background Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood. Methods Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. Results The odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% −23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI −20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome. Conclusions Measures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

scholarly journals Urinary Catalytic Iron in Obesity

2011 ◽  
Vol 57 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Tina K Thethi ◽  
Kaushik Parsha ◽  
Mohan Rajapurkar ◽  
Banibrata Mukhopadhyay ◽  
Sudhir Shah ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Body Mass ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Waist To Hip Ratio ◽  
Study Results ◽  
Significant Difference

INTRODUCTION Obesity precedes the development of many cardiovascular disease risk factors, including type 2 diabetes mellitus (DM), hypertension, and chronic kidney disease. Catalytic iron, which has been associated with these chronic diseases, may be one of the links between obesity and these multifactorial diverse disorders. OBJECTIVE We investigated whether urinary catalytic iron is increased in obese individuals without DM and overt kidney disease. STUDY DESIGN We measured urinary catalytic iron using established methods in 200 randomly selected individuals without DM [100 who were obese (body mass index ≥30 kg/m2) and 100 who were nonobese (body mass index ≤27)]. Participants were selected from an outpatient clinic and community setting and were part of an ongoing cross-sectional study of obesity in individuals between the ages of 18 and 70 years. RESULTS There was a significant difference in mean (95% CI) urinary catalytic iron excretion between the obese participants and the nonobese participants, 463 (343–582) nmol/mg [52.3 (38.8–65.8) nmol/μmol] vs 197 (141–253) nmol/mg [22.3 (15.9–28.6) nmol/μmol]; P &lt; 0.001. The significant predictors of increased urinary catalytic iron were obesity (P = 0.001) and waist-to-hip ratio (P = 0.03). CONCLUSIONS Our study results demonstrate that obesity and waist-to-hip ratio are associated with increased urinary catalytic iron, which may be a useful marker of oxidative stress. Additional studies are needed to determine the role of catalytic iron in increased cardiovascular disease and chronic kidney disease associated with obesity.

The 4G/5G Sequence Polymorphism in the Promoter of Plasminogen Activator Inhibitor-1 (PAI-1) Gene: Relationship to Plasma PAI-1 Level in Venous Thromboembolism

1998 ◽  
Vol 79 (05) ◽  
pp. 975-979 ◽  
Author(s):  
Mojca Stegnar ◽  
Pavel Uhrin ◽  
Polona Peternel ◽  
Alenka Mavri ◽  
Barbara Salobir-Pajnič ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Plasminogen Activator ◽  
Body Mass ◽  
Plasminogen Activator Inhibitor ◽  
Healthy Controls ◽  
Metabolic Factors ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

SummaryImpaired fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) is observed in up to 40% of patients with venous thromboembolism and might be causally related to the disease. There is evidence that genetic variations in the promoter of the PAI-1 gene and metabolic factors contribute to increased plasma PAI-1 levels.A single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene and metabolic factors were studied in 158 unrelated patients below the age of 61 years (43 ± 11 years, mean ± standard deviation) with history of objectively confirmed venous thromboembolism and in 145 apparently healthy controls.Patients had on average two times higher PAI activity (11.9 vs. 6.1 IU/ml) and by 40% higher PAI-1 antigen (14.8 vs. 10.7 ng/ml) than healthy controls, and also higher body mass index, lipid levels, fasting glucose and insulin. Patients differed significantly from healthy controls neither in the frequency of the 4G and 5G alleles (0.57/0.43 in patients and 0.52/0.48 in controls) nor in the distribution of the 4G/5G genotypes. Possession of the 4G/4G or the 4G/5G genotype did not increase relative risk for venous thromboembolic disease and the distribution of the 4G/5G genotypes was neither associated with recurrent nor with spontaneous disease. In patients association between the 4G/5G genotypes and PAI activity (adjusted for body mass index, triglyceride and glucose level) was observed, with the highest PAI activity values in the 4G/4G genotype (14.6 IU/ml), intermediate in the 4G/5G genotype (13.3 IU/ml) and the lowest in the 5G/5G genotype (5.2 IU/ml, all values means). Association between PAI activity and triglyceride level was the strongest in the 4G/4G genotype (correlation coefficient r = 0.47, p <0.01) and the weakest in the 5G/5G genotype (r = -0.04, not significant).In conclusion, the present case-control study shows an association between the 4G/5G polymorphism in the promoter of the PAI-1 gene and plasma PAI-1 levels in patients with venous thromboembolism. Similar distribution of the 4G/5G genotypes in patients and healthy controls suggests that this genetic variation by itself is not a major risk factor for venous thromboembolism.

scholarly journals Obesity without Established Comorbidities of the Metabolic Syndrome Is Associated with a Proinflammatory and Prothrombotic State, Even before the Onset of Puberty in Children

2010 ◽  
Vol 95 (3) ◽  
pp. 1060-1068 ◽  
Author(s):  
Nelly Mauras ◽  
Charles DelGiorno ◽  
Craig Kollman ◽  
Keisha Bird ◽  
Melissa Morgan ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Plasminogen Activator ◽  
Body Mass ◽  
Plasminogen Activator Inhibitor ◽  
Obese Children ◽  
Prothrombotic State ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

Abstract Background: Metabolic syndrome (MS)-related comorbidities in obesity, such as hypertension, dyslipidemia, and glucose intolerance, are increasingly recognized in children, predisposing them to early cardiovascular disease. Objective: The objective of the study was to investigate whether markers of inflammation and prothrombosis are abnormal in obese children without established MS comorbidities across puberty, as compared with lean, age-matched controls. Subjects and Methods: Obese children (body mass index &gt;95%) with normal fasting glucose, blood pressure, cholesterol and triglycerides were recruited; lean controls (body mass index 10–75%) had no first-degree relatives with MS. High-sensitivity C-reactive protein (hsCRP), IL-6, plasminogen activator inhibitor 1, and fibrinogen concentrations were measured. Body composition was assessed by waist circumference and dual-energy x-ray absorptiometry. Results: Of 623 children screened, 203 enrolled (106 males, 97 females), aged 7–18 yr, 115 obese, 88 lean (balanced for age and gender), 99 prepubertal, and 104 pubertal. Many screen failures were due to silent comorbidities. Obese subjects with insulin resistance but without MS comorbidities had about 10 times higher hsCRP concentrations than controls and higher fibrinogen, IL-6, and plasminogen activator inhibitor-1 (P &lt; 0.01 all). Differences were significant, even in the prepubertal cohort. hsCRP and fibrinogen correlated with waist circumference (r = 0.73 and 0.40, respectively) and percent fat mass (r = 0.76 and 0.47) (P &lt; 0.0001). Conclusion: Childhood obesity per se is associated with a proinflammatory and prothrombotic state before other comorbidities of the MS are present and even before the onset of puberty. Whether biomarkers like hsCRP and fibrinogen are useful in assessing cardiovascular risk and whether these abnormalities are reversible with earlier therapeutic interventions in very young obese children requires further study.

scholarly journals Associations of Fibrinogen, Factor VII and PAI-1 with Baseline Findings among 10,500 Male Participants in a Prospective Study of Myocardial Infarction

1998 ◽  
Vol 80 (11) ◽  
pp. 749-756 ◽  
Author(s):  
Marie-Francoise Aillaud ◽  
Philippe Amouyel ◽  
Alun Evans ◽  
Gérald Luc ◽  
Jean Ferrières ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Northern Ireland ◽  
Cardiovascular Risk Factors ◽  
Factor Vii ◽  
Waist To Hip Ratio ◽  
Leisure Physical Activity ◽  
Pai 1

SummaryThe contribution of coagulation factors and fibrinolytic variables to the development of ischaemic arterial disease is still not clearly established. The PRIME study is a prospective cohort study of myocardial infarction in men aged 50-59 years and recruited from three MONICA field centers in France (Lille, Strasbourg and Toulouse) and the center in Northern Ireland (Belfast). Baseline examination included measurement of plasma fibrinogen, factor VII, and PAI-1 activity in over 10,500 participants. We investigated the associations of these haemo-static variables with cardiovascular risk factors, prevalent atherosclerotic disease and geographical area. Fibrinogen level increased with age, smoking, waist-to-hip ratio, LDL-cholesterol, and it decreased with educational level, leisure physical activity, alcohol intake and HDL-cholesterol. Factor VII activity increased with body mass index, waist-to-hip ratio, triglycerides, HDL- and LDL-cholesterol. PAI-1 activity increased with body mass index, waist-to-hip ratio, triglycerides, alcohol intake, smoking, and decreased with leisure physical activity. PAI-1 level was higher in diabetic subjects than in subjects without diabetes. Cardiovascular risk factors explained 8%, 9%, and 26% of the total variance in fibrinogen, factor VII, and PAI-1, respectively. Compared with participants without prevalent cardiovascular disease, those with previous myocardial infarction (n = 280), angina pectoris (n = 230), or peripheral vascular disease (n = 19) had significantly higher levels of fibrinogen, but those with stroke (n = 67) had not. PAI-1 activity showed a similar pattern of association. The odds ratio for cardiovascular disease associated with a rise of a one standard deviation in fibrinogen and PAI-1 was 1.31 (95% confidence interval: 1.20 to 1.42, p <0.001) and 1.38 (95% confidence interval: 1.27 to 1.49, p <0.001), respectively. After adjustment for cardiovascular risk factors, these associations were attenuated but remained highly significant. There was no significant association between factor VII activity and prevalent cardiovascular disease. Fibrinogen level and, to a lesser extent, factor VII and PAI-1 activity were higher in Northern Ireland than France after adjustment for the main cardiovascular risk factors. These geographical variations are consistent with the 2 to 3-fold higher incidence of myocardial infarction in Northern Ireland than France. Our results provide further epidemiological evidence for a possible role of fibrinogen and PAI-1 in the pathogenesis of coronary heart disease.

Sign in / Sign up

Export Citation Format

Share Document