Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study

Meade, T. W.; Ruddock, V; Stirling, Yvonne; Chakrabarti, Ranjan; Miller, George

doi:10.1016/0140-6736(93)92062-x

Cited by 688 publications

(375 citation statements)

References 26 publications

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“…From a baseline level almost twice that of healthy middle-aged non-obese individuals, FVIIc was lowered 12%, corresponding to an estimated 10 ±20% risk reduction (Meade et al, 1986). Plasma ®brinogen declined by 6% which might lower the risk of future CHD another 10% (Meade et al, 1986;Meade et al, 1993). We would expect that the 34% lowering of PAI-1, the main inhibitor of endogenous ®brinolysis, also would contribute (Gram et al, 1987;Hamsten et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Sustained improvement in blood lipids, coagulation, and fibrinolysis after major weight loss in obese subjects

Marckmann¹,

Toubro²,

Astrup³

1998

Eur J Clin Nutr

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Objective: To study whether major weight loss causes sustained improvement in blood lipids and haemostatic pro®le in obese subjects, and to compare the in¯uence of two different slimming and maintenance regimens. Design: Two-stranded randomized intervention study. Setting: University Department. Subjects: Thirty-six out of 43 obese patients recruited from out-patient waiting list completed the study. Interventions: Weight loss was achieved by very low energy formula diet (2 MJad for 8 weeks, n 18), or lowenergy conventional diet (5 MJad for 17 weeks, n 18), both combined with anorectic compound. Participants were re-randomized to consume low fat diet ad libitum (n 16), or energy-restricted diet (n 20) for weight maintenance during 24 weeks. Main outcome measures: Plasma lipids, ®brinogen, factor VII coagulant activity (FVIIc), and plasminogen activator inhibitor type 1 (PAI-1) antigen. Results: Weight loss averaged 13.6 kg (95% CI: 12.3 ± 14.9 kg). After 24 weeks' weight maintenance, plasma total cholesterol was 9% lower, high density lipoprotein cholesterol 5% higher, triglycerides 30% lower, FVIIc 12% lower, ®brinogen 6% lower, and PAI-1 antigen 34% lower than at baseline (all changes highly signi®cant). There were no signi®cant differences between slimming or maintenance regimens. Conclusions: Major weight loss is associated with sustained and marked improvements in blood lipids and hemostatic pro®le, irrespective of the tested slimming and maintenance regimens.

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Section: Discussionmentioning

confidence: 99%

Sustained improvement in blood lipids, coagulation, and fibrinolysis after major weight loss in obese subjects

Marckmann¹,

Toubro²,

Astrup³

1998

Eur J Clin Nutr

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“…Smoking is associated with increased levels of procoagulative factors, e.g. fibrinogen [35] and reduced fibrinolytic capacity [36], while moderate alcohol consumption has been shown to influence the levels of fibrinolytic factors [37][38][39]. In fact haemostatic factors have been suggested to be on the eventual pathway to the protective effect of alcohol.…”

Section: Discussionmentioning

confidence: 99%

Alcohol and coronary heart disease: the roles of HDL‐cholesterol and smoking

Mänttäri

Tenkanen²,

Alikoski³

et al. 1997

Journal of Internal Medicine

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Abstract. Man$ tta$ ri M, Tenkanen L, Alikoski T, Manninen V (Department of Medicine, Helsinki University and Helsinki Heart Study, Helsinki, Finland). Alcohol and coronary heart disease : the roles of HDL-cholesterol and smoking. J. Intern Med 1997 ; 241 : 157-63. Objectives.To study the role of HDL-cholesterol (HDLc) in the causal pathway mediating the effect of alcohol on coronary heart disease (CHD). Design. Cox proportional hazard models were used to compare the relative CHD risks in various HDLcsmoking categories. Setting. A prospective, multicentre, placebocontrolled, double-blind CHD primary prevention trial with gemfibrozil in primary (occupational) health care units, the Helsinki Heart Study. Subjects. Dyslipidaemic middle-aged men with available alcohol consumption data (1924 of 2035) in the placebo arm of the 5-year study. Main outcome measures. Seventy-seven (of 84) cases of nonfatal myocardial infarction or cardiac death.

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“…5,37 A number of clinical studies have shown an increase in TF-mediated coagulation and in factor VII activity/antigen in obese and NIDDM patients. [38][39][40] In preliminary studies, we demonstrated that TF mRNA expression also is elevated in the epididymal and subcutaneous fat pads from obese mice compared with their lean counterparts. 41 TF expression in adipose tissue was localized to adipocytes, adventitial cells surrounding blood vessels, and other unidentified stromal vascular cells.…”

Section: Other Hemostatic Genesmentioning

confidence: 99%

The Adipocyte and Hemostatic Balance in Obesity

Loskutoff

Samad

1998

ATVB

258

157

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P lasminogen activator inhibitor 1 is the primary physiological inhibitor of plasminogen activation in vivo, and elevations in plasma PAI-1 appear to compromise normal fibrin clearance mechanisms and promote thrombosis. PAI-1 is dramatically upregulated in obesity, a complex condition associated with increased risk for myocardial infarction, accelerated atherosclerosis, hypertension, glucose intolerance, insulin resistance, hyperinsulinemia, and NIDDM. In spite of the apparent link between elevated PAI-1 levels and thrombotic disease, little is known about the origin of this plasma inhibitor in obesity/NIDDM or about the signals that control its biosynthesis. Potential insights into the underlying molecular events have come from recent studies of genetically obese mice and of cultured adipocytes. These studies are reviewed here.* They emphasize the key role played by the adipocyte, a cell whose numbers, size, and metabolic activity are grossly altered in obesity/NIDDM. They also suggest that multiple cytokines, hormones, and growth factors may be involved, and they raise the possibility that the abnormal expression of other hemostatic genes by adipocytes in obesity/NIDDM may also contribute to the cardiovascular complications of this disorder. In this regard, our preliminary studies indicate that TF gene expression is elevated in the adipose tissues of the obese mouse. Properties of PAI-1PAI-1 appears to be the primary physiological inhibitor of plasminogen activation in blood, since it is the only PAI found complexed with single-chain tissue-type PA in carefully collected human plasma, and the second-order rate constant for its interaction with tissue-type PA and urokinase-type PA (Ϸ3.5ϫ10 7 [mol/L] Ϫ1 ⅐ s Ϫ1 ) is at least two orders of magnitude higher than that of other PAIs. [1][2][3][4] The normal concentration of PAI-1 protein in human plasma ranges from 6 to 80 ng/mL with a geometric mean at 24 ng/mL, whereas that of tissuetype PA is 5 to 10 ng/mL. Abnormalities in the concentration of PAI-1 are frequently associated with vascular disease. For example, the inhibitor is elevated in a variety of thrombotic conditions, including myocardial infarction and deep venous thrombosis. Elevated PAI-1 also correlates with thrombosis in animal models, and transgenic mice that overexpress PAI-1 have been reported to develop venous thrombosis. 5 On the other hand, the absence of PAI-1 in humans leads to life-long bleeding problems presumably resulting from the development of a hyperfibrinolytic state, and disruption of the PAI-1 gene in mice is also associated with a mild hyperfibrinolytic state as manifested by increased resistance to endotoxin-induced thrombosis. 5 Finally, neutralizing plasma PAI-1 activity with specific antibodies or by the use of PAI-1 inhibitors 4,6 enhances spontaneous or tissue-type PA-mediated thrombolysis. These observations emphasize that imbalances in the PA/PAI-1 ratio are likely to promote either thrombosis or bleeding. As summarized in the next section, this balance is severely disturbed ...

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Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study

Cited by 688 publications

References 26 publications

Sustained improvement in blood lipids, coagulation, and fibrinolysis after major weight loss in obese subjects

Sustained improvement in blood lipids, coagulation, and fibrinolysis after major weight loss in obese subjects

Alcohol and coronary heart disease: the roles of HDL‐cholesterol and smoking

The Adipocyte and Hemostatic Balance in Obesity

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