Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men.

Yang, Xiaochun; Jing, Tian-Yi; Resnick, Lawrence M.; Phillips, Gerald B.

doi:10.1161/01.atv.13.4.467

Cited by 63 publications

(27 citation statements)

References 47 publications

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“…Furthermore, although several 8 -17 but not all 18 -23 previous cross-sectional epidemiological studies reported a positive association between plasma fibrinogen level and elevated BP and/or prevalent hypertension, most previous studies reporting a positive association were confined to men. 8,11,13,[15][16][17] Among women, our finding of a positive association between plasma fibrinogen and hypertension in crosssectional analysis but null association in prospective analysis is similar to the results from the ARIC Study. 24 This finding probably reflects the plasma fibrinogen elevation secondary to increase in shear stress, endothelial dysfunction, and progressive vascular disease in severe hypertension.…”

Section: Discussionsupporting

confidence: 86%

Positive Association Between Plasma Fibrinogen Level and Incident Hypertension Among Men

Shankar

Wang²,

Rochtchina³

2006

Hypertension

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Abstract-Elevated plasma fibrinogen is implicated in cardiovascular disease. However, it is not clear whether fibrinogen levels predict the development of hypertension. We examined the relationship between plasma fibrinogen level and hypertension in a population-based cohort study of 3654 participants (mean age: 61.5 years; range: 49 to 84 years) at the baseline examination (1992)(1993)(1994) in the Blue Mountains region, west of Sydney, Australia, who were examined 5 years (1997)(1998)(1999) later. Main outcomes of interest were prevalent hypertension (systolic blood pressure Ն140 mm Hg, diastolic blood pressure Ն90 mm Hg, or a combination of self-reported hypertension diagnosis and use of antihypertensive medications) at baseline (nϭ2212/3180) and 5-year incidence of hypertension among baseline normotensive individuals (nϭ361/637). Elevated plasma fibrinogen level was positively associated with prevalent hypertension both among men and women and positively associated with 5-year incident hypertension among men, independent of several cardiovascular risk factors. Multivariable odds ratio (95% CI) of 5-year incident hypertension comparing tertile 3 of plasma fibrinogen (Ն3.9 g/L) with tertile 1 (Յ3.2 g/L) was 1.95 (1.03 to 3.68; P trendϭ0.040). This prospective association, however, was not observed in women (odds ratio; 95% CI) comparing tertile 3 versus tertile 1 of plasma fibrinogen (1.00; 0.54 to 1.86; P trendϭ0.986). Subgroup analyses stratified by smoking, body mass index, diabetes, and blood pressure categories supported this male gender-specific pattern of association. These data provide prospective epidemiological evidence of an essential link between plasma fibrinogen level and incident hypertension among men but not among women, a finding consistent with that observed in the Atherosclerosis Risk in Communities Study. A cross several studies, plasma fibrinogen is a consistent predictor of cardiovascular disease, 1-3 subclinical atherosclerosis, 4 -6 peripheral vascular disease, 7 and decreased survival. 3 Several 8 -17 but not all 18 -23 previous cross-sectional epidemiological studies reported a positive association between plasma fibrinogen level and elevated blood pressure and/or prevalent hypertension. In contrast, the only prospective study available on this topic by Folsom et al 24 reported that plasma fibrinogen level predicted 6-year incident hypertension among middle-aged men only, but not women, in the biracial Atherosclerosis Risk In Communities (ARIC) Study. The prospective association between plasma fibrinogen level and incident hypertension is still not clear, particularly by gender. In this report, we examined the association between plasma fibrinogen level and 5-year incident hypertension among men and women in an older Australian population, after adjusting for smoking, alcohol intake, body mass index (BMI), and other cardiovascular risk factors. MethodsThe Blue Mountains Eye Study (BMES) is a population-based cohort study of age-related eye diseases and other health outcomes in an old...

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Section: Discussionsupporting

confidence: 86%

Positive Association Between Plasma Fibrinogen Level and Incident Hypertension Among Men

Shankar

Wang²,

Rochtchina³

2006

Hypertension

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“…Associations between sex hormones and plasma PAI-1 activity could partly explain these findings. In men, serum testosterone level 38 -39 is inversely and the serum estradiol-to-testosterone ratio 38 is positively correlated with plasma PAI-1 activity. Furthermore, in men the association between serum testosterone and serum estradiol-to-testosterone ratio and plasma PAI-1 activity was markedly stronger than the relationship between plasma insulin and PAI-1 activity in one study.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in men the association between serum testosterone and serum estradiol-to-testosterone ratio and plasma PAI-1 activity was markedly stronger than the relationship between plasma insulin and PAI-1 activity in one study. 38 Nevertheless, in normoglycemic men low testosterone level is related to high insulin 40 and in diabetic men to high triglyceride 41 concentrations, which could be mediators between testosterone level and PAI-1 activity. It is not known how sex hormones are related to plasma PAI-1 activity in women.…”

Section: Discussionmentioning

confidence: 99%

Insulin sensitivity is not an independent determinant of plasma plasminogen activator inhibitor-1 activity.

Mykkänen

Rönnemaa

Marniemi

et al. 1994

Arterioscler Thromb

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It recently has been hypothesized that increased plasma plasminogen activator inhibitor-1 (PAI-1) activity could be a possible link between insulin resistance and coronary heart disease. However, it is not known whether insulin sensitivity per se is a determinant of plasma PAI-1 activity or whether other intermediates could explain this association. We investigated the relationship between plasma PAI-1 activity and insulin sensitivity, obesity, distribution of body fat, blood pressure, plasma insulin concentration, and serum lipid levels in normoglycemic men (n=61) and women (n=77) 53 to 61 years old who participated in a previous population-based study. Insulin sensitivity was estimated by the minimal model from a frequently sampled intravenous glucose tolerance test. In univariate analyses, PAI-1 correlated positively with body mass index, waist-to-hip ratio (WHR), fasting and 2-hour insulin levels, and triglyceride level in both men and women. Furthermore, in women PAI-1 correlated inversely with highdensity lipoprotein (HDL) cholesterol level. There was an I mpairment of fibrinolysis has recently emerged as a risk factor for ischemic heart disease. Coronary artery thrombus formation plays a critical role in the pathogenesis of both unstable angina 1 and myocardial infarction (MI).2 Fibrinolytic activity in blood is regulated mainly by plasma plasminogen activator inhibitor-1 (PAI-1).3 Increased levels of PAI-1 have been demonstrated in survivors of acute MI 45 and in patients with angiographically verified coronary heart disease (CHD). 67 Moreover, an elevated plasma PAI-1 level has been shown to be a risk factor for myocardial reinfarction in men under the age of 45. inverse relationship between PAI-1 and insulin sensitivity (r=-.39, /><.01 in men; r=-.38, P<.00l in women). In multivariate analyses in men, insulin sensitivity failed to show any significant association with PAI-1. In contrast, triglyceride level and body mass index were independently associated with PAI-1. Also in women, insulin sensitivity was not independently associated with PAI-1. In women, WHR and HDL cholesterol concentration or WHR and 2-hour insulin concentration were independently related to PAI-1. In conclusion, obesity, central body fat distribution, and serum triglyceride and HDL cholesterol concentrations explained the association between insulin sensitivity and plasma PAI-1 activity in normoglycemic subjects. In addition, our findings suggest that the major correlates of plasma PAI-1 activity may be different in men and women. with untreated mild hypertension 15 -17 have elevated PAI-1 levels. These factors also are features of the insulin resistance syndrome, 1819 and it has been hypothesized that an increased plasma PAI-1 level could be a possible link between insulin resistance and CHD. 20 PAI-1 level consistently has shown an inverse correlation with insulin sensitivity in univariate analyses 11121721 ; however, findings of the two studies 12 -21 that reported results of multivariate analyses were contradictory. ...

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“…Thus, androgen levels correlate positively with tissue plasminogen activator activity, which stimulates fibrinolysis, and inversely with plasminogen activator inhibitor activity and fibrinogen (33,44,70,139,191). Interestingly, in bovine aortic endothelial cells, testosterone, at pharmacological doses, inhibited the secretion of plasminogen activator and stimulated secretion of plasminogen activator inhibitor type I (164).…”

Section: Androgens and The Hemostatic Systemmentioning

confidence: 99%

Cardiovascular Effects of Androgens

Weidemann

Hanke

2002

Cardiovascular Drug Reviews

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In the process of atherosclerosis sex steroids play a complex role in the vascular vessel wall system. Although a number of experimental studies have clearly documented an atheroprotective effect of estrogens, in recent clinical studies, estrogen replacement therapy has failed to reduce cardiovascular mortality. The effects of androgens on the cardiovascular system and cardiovascular diseases are even more controversial. Whereas in the past, androgens were mainly believed to exert adverse effects on the cardiovascular system, recent studies in men have documented a number of beneficial actions of testosterone in the arterial vascular system. Androgens affect lipid metabolism (e.g., LDL and HDL cholesterol, Lp(a)) and hemostasis (e.g., platelet aggregation and fibrinolytic activity). In addition, several other physiological and pathophysiological processes in the arterial vessel wall are influenced by androgens. Acute hemodynamic effects of testosterone on coronary vasomotion and stress-test-induced ischemia were reported. Additionally, recent animal and in vitro studies have further documented an inhibitory effect of androgens on neointimal plaque formation. This review discusses different and, in part, contradictory effects of androgens on the cardiovascular system including potential signal transduction pathways in androgen target cells.

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Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men.

Cited by 63 publications

References 47 publications

Positive Association Between Plasma Fibrinogen Level and Incident Hypertension Among Men

Positive Association Between Plasma Fibrinogen Level and Incident Hypertension Among Men

Insulin sensitivity is not an independent determinant of plasma plasminogen activator inhibitor-1 activity.

Cardiovascular Effects of Androgens

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