American Journal of Epidemiology Vol. 152, No. 10 : 912
Copyright © 2000 by The Johns Hopkins University School of Hygiene and Public Health
ORIGINAL CONTRIBUTIONS |
An Author Responds to Meigs' Invited Commentary
From the Departments of Pathology and Biochemistry, College of Medicine, University of Vermont, Burlington, VT.
Abbreviations:
PAI-1, plasminogen activator inhibitor-1; PAP, plasmin-
2-antiplasmin
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In his commentary (1
), Dr. Meigs has provided an excellent review of factor analysis, specifically as it pertains to this metabolic syndrome. I shall briefly address several of his comments.
First, the final position of plasminogen activator inhibitor-1 (PAI-1) in our study (2) was of particular interest, given the known associations of PAI-1 with obesity (3), insulin (4), and inflammation (5). The respective loadings for these three factors were 0.44, 0.34, and -0.03, clearly indicating the stronger relations. Given the increasing interest in PAI-1 as an etiologic agent in disease progression (6), these findings have important health implications.
Second, I agree with Dr. Meigs that it was surprising to see C-reactive protein emerge as "independent" of body mass, especially given that this cohort was used in one of the first analyses to describe the association of C-reactive protein levels with body mass index (7). However, while the loading for inflammation was 0.62, the loading for body mass was 0.28, indicating some degree of association. It has been suggested that the association of C-reactive protein with body mass index is mediated by inflammatory cytokines ("inflammation") (8)—a position only weakly supported by these data, in my opinion.
Third, we interpreted the loading of plasmin-2-antiplasmin (PAP), a marker of plasmin generation, on body mass (-0.34) as being mediated, at least in part, by the negative association of PAP with PAI-1 (r = -0.20). To our knowledge, two things drive PAP levels: PAI-1 (negatively), by limiting plasmin generation, and fibrin production (positively), by stimulating plasminogen activation (9). However, fibrin fragment D-dimer, a marker of plasmin activity, was much less dependent on PAI-1 (r = 0.01) and showed virtually no loading on the body mass factor (0.08). Viewed this way, PAP is a marker of fibrinolysis that incorporates body mass and PAI-1 levels, while fibrin fragment D-dimer is a marker of fibrinolysis which relies principally on fibrin generation. In further support of this position, fibrin fragment D-dimer also loaded on the procoagulation factor (0.48), while PAP did not (0.16).
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NOTES |
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Reprint requests to Dr. Russell P. Tracy, University of Vermont College of Medicine, 208 South Park Drive, Suite 2, Colchester, VT 05446 (e-mail: rtracy{at}salus.med.uvm.edu).
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REFERENCES |
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Meigs JB. Invited commentary: Insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 2000;152:908–11.
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Sakkinen PA, Wahl P, Cushman M, et al. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol 2000;152:897–907.
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Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 1998;18:1–6.
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Juhan-Vague I, Alessi MC, Joly P, et al. Plasma plasminogen activator inhibitor-1 in angina pectoris: influence of plasma insulin and acute-phase response. Arteriosclerosis 1989;9:362–7.
[Abstract/Free Full Text] - Kluft C, Verheijen JH, Jie AF, et al. The postoperative fibrino-lytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma. Scand J Clin Lab Invest 1985;45:605–10.[ISI][Medline]
- Plow EF, Ploplis VA, Busuttil S, et al. A role of plasminogen in atherosclerosis and restenosis models in mice. Thromb Haemost 1999;82(suppl 1):4–7.
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Tracy RP, Psaty BM, Macy E, et al. Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. Arterioscler Thromb Vasc Biol 1997;17:2167–76.
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Yudkin JS, Stehouwer CD, Emeis JJ, et al. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999;19:972–8.
[Abstract/Free Full Text] -
Sakkinen PA, Cushman M, Psaty BM, et al. Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women. Arterioscler Thromb Vasc Biol 1999;19:499–504.
[Abstract/Free Full Text]
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- Clustering of Procoagulation, Inflammation, and Fibrinolysis Variables with Metabolic Factors in Insulin Resistance Syndrome
- Pamela A. Sakkinen, Patricia Wahl, Mary Cushman, Michael R. Lewis, and Russell P. Tracy
Am. J. Epidemiol. 2000 152: 897-907.[Abstract] [FREE Full Text] - Invited Commentary: Insulin Resistance Syndrome? Syndrome X? Multiple Metabolic Syndrome? A Syndrome At All? Factor Analysis Reveals Patterns in the Fabric of Correlated Metabolic Risk Factors
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