Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group.

Abstract

a major indicator of insulin resistance, may exert its influence on the risk of coronary artery disease partially through disturbances of the hemostatic system. The relations of fasting insulin concentrations with the degree of coronary atherosclerosis, other coronary risk factors (including some markers of the insulin resistance syndrome such as body mass index and triglyceride), markers of inflammation, and hemostatic factors were investigated in 1484 patients with angina pectoris. Mean insulin levels were higher in patients with one or more coronary vessel stenoses than in those without (9.9 fiU/mL compared with 9.0 fiV/mh, P<.0001). However, the association with the presence of vessel stenoses was stronger in patients with a previous myocardial infarction than in those without. Insulin increased markedly (P<.0001) and independently of other risk factors with age, body mass index, triglyceride concentration, and markers of inflammation, such as white blood cell count and C-reactive protein. The strongest relations between insulin and hemostatic factors were observed with fibrinolytic variables, particularly plasminogen activator inhibitor-1 (PA1-1) levels (r=.44, P<.0001). This relation decreased somewhat (r=.29) after simultaneous adjustment for markers of the insulin resistance syndrome, mainly body mass index and triglycerides, but not after adjustment for markers of inflammation. Therefore, we propose that increased PAI-1 levels, which are essentially related to the classic metabolic aspect of the insulin resistance syndrome, have to be included in this syndrome. Insulin concentrations were also significantly related to a lesser extent with hemostatic variables that are considered as acute-phase markers, such as fibrinogen, von Willebrand factor, and factor VIII: c; these correlations were independent of joint associations with other coronary risk factors, including body mass index and triglyceride. Simultaneous adjustments for markers of inflammation substantially reduced the fibrinogen relation to insulin but only slightly modified those between insulin and von Willebrand factor and factor VIII :c. These results indicate that the insulin-fibrinogen relation is more related to the accompanying acute-phase reaction, whereas the link between insulin and von Willebrand factor and factor VIII: c may be due to nonspecific endothelial cell damage. (Arterioscler Thromb. 1993; 13:1865-1873.) KEY WORDS • hemostatic system • plasminogen activator inhibitor-1 • fibrinogen • von Willebrand factor • factor VIII • insulin resistance • insulin • arteriosclerosis • angina pectoris • risk factors A therosclerosis appears to be caused by a number / \ of interacting factors, including disturbed lipid A. \. metabolism, endothelial cell damage, hemo-static changes, monocyte invasion, and smooth muscle cell proliferation. Many clinical studies have also shown increased fasting insulin levels or insulin response to a glucose challenge in patients with ischemia of the heart, lower limbs, or brain (for a review, see Reference 1)...

Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome

“…For that reason, we support again the 10-year-old suggestion by Juhan-Vague et al 27 to definitely accept increased PAI-1 levels as a true component of the metabolic syndrome. The two recent working definitions of the metabolic syndrome 3,4 did not include increased levels of PAI-1 as a criterion for the definition of the metabolic syndrome since they did not find it necessary for the recognition of the condition 3 or because it cannot be identified by routine clinical evaluation.…”

Elevated C-Reactive Protein

“…Relationships between CRP concentrations and fasting insulin levels have been observed in some studies, [11][12][13][14]43,44 and this association has been shown to persist after adjustment for BMI. 14 In the present study, we also found a relationship between CRP concentrations and insulinemia (a crude marker of insulin resistance in nondiabetic subjects), suggesting that hyperinsulinemia resulting from insulin resistance is also associated with a state of low chronic inflammation.…”

Metabolic Syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study

“…In this regard, our data are consistent with reports relating insulin resistance not only with diabetes, dyslipidemia, hypertension, central obesity and microalbuminuria, but also hyperuricemia, hyperleptinemia, endothelial dysfunction, inflammatory status, thrombophilia, oxidative stress and liver steatosis. [42][43][44][45][46][47][48] In conclusion, the coexistence of multiple metabolic disorders in the single individual, also called Metabolic Syndrome, occurs very frequently in the general population. The syndrome is associated with several nonmetabolic abnormalities documenting thrombophilia, increased oxidative stress, inflammation, endothelial dysfunction, liver steatosis and leptin resistance.…”