@article {1570, title = {Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.}, journal = {Thromb Haemost}, volume = {80}, year = {1998}, month = {1998 Jul}, pages = {134-9}, abstract = {

The majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Antithrombin, Protein C, Protein S. and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women > or = 65 years) free of clinical cardiovascular disease (CVD). We did not observe any strong age-associated trends, although Protein C was lower in older women (p < or = 0.001), and TFPI was higher in older men (p < or = 0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen. plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin complex; LDL-cholesterol; and carotid wall thickness (R2 for the model = 0.35). In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Anticoagulants, Antithrombin III, Biomarkers, Cross-Sectional Studies, Disease Susceptibility, Female, Humans, Lipoproteins, Male, Prevalence, Protein C, Protein S, Reference Values, Risk Factors, Thrombosis}, issn = {0340-6245}, author = {Sakkinen, P A and Cushman, M and Psaty, B M and Kuller, L H and Bajaj, S P and Sabharwal, A K and Boineau, R and Macy, E and Tracy, R P} } @article {1522, title = {Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology.}, journal = {Am J Epidemiol}, volume = {149}, year = {1999}, month = {1999 Feb 01}, pages = {261-7}, abstract = {

An increasing number of cardiovascular epidemiologic studies are measuring non-traditional risk markers of disease, most of which do not have established biovariability characteristics. When biovariability data have been reported, they usually represent a short time period, and, in any case, there is little consensus on how the information should be used. The authors performed a long-term (6-month) repeated measures study on 26 healthy individuals, and, using a nested analysis of variance (ANOVA) approach, report on the analytical (CVA), intraindividual (CVI), and between individual (CVG) variability of 12 procoagulant, fibrinolysis, and inflammation assays, including total cholesterol for comparison. The results suggest acceptable analytical variability (CVA < or = 1/2 CVI) for all assays. However, there was a large range of intraindividual variation as a proportion of total variance (2-78\%), and adjusting for intraindividual and between individual variation in bivariate correlations increased the observed correlation by more than 30 percent for three of these assays. Overall, the assays showed a significant increase in intraindividual variation over 6 months (p < 0.05). While these findings suggest that most of these assays have biovariability characteristics similar to cholesterol, there is variation among assays. Some assays may be better suited to epidemiologic studies, and knowledge of an assay{\textquoteright}s biovariability data may be useful in interpreting simple statistics, and in designing multivariate models.

}, keywords = {Adult, Aged, Analysis of Variance, Cardiovascular Diseases, Cholesterol, Epidemiology, Female, Fibrinolysis, Hemostasis, Humans, Inflammation, Male, Middle Aged, Models, Statistical, Multivariate Analysis, Risk Factors}, issn = {0002-9262}, author = {Sakkinen, P A and Macy, E M and Callas, P W and Cornell, E S and Hayes, T E and Kuller, L H and Tracy, R P} } @article {585, title = {Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Mar}, pages = {499-504}, abstract = {

Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, }, keywords = {Aged, Aged, 80 and over, alpha-2-Antiplasmin, Antifibrinolytic Agents, Asian Continental Ancestry Group, Cohort Studies, Coronary Disease, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Fibrinolysin, Fibrinolysis, Humans, Insulin Resistance, Male, Multivariate Analysis, Myocardial Infarction, Plasminogen Activator Inhibitor 1, Risk Factors}, issn = {1079-5642}, doi = {10.1161/01.atv.19.3.499}, author = {Sakkinen, P A and Cushman, M and Psaty, B M and Rodriguez, B and Boineau, R and Kuller, L H and Tracy, R P} } @article {626, title = {Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome.}, journal = {Am J Epidemiol}, volume = {152}, year = {2000}, month = {2000 Nov 15}, pages = {897-907}, abstract = {

The known metabolic cardiovascular disease risk factors associated with insulin resistance syndrome (IRS) do not adequately explain the excess cardiovascular disease risk attributed to this syndrome, and abnormalities in hemostatic variables may contribute to this excess risk. Using data from 322 nondiabetic elderly men and women (aged 65-100 years) participating in the Cardiovascular Health Study during 1989-1990, the authors performed factor analysis on 10 metabolic risk factors associated with IRS and 11 procoagulation, inflammation, and fibrinolysis variables to examine the clustering of the metabolic and hemostatic risk markers. Factor analysis of the metabolic variables confirmed four uncorrelated factors: body mass, insulin/glucose, lipids, and blood pressure. Adding the hemostatic variables yielded three new factors interpreted as inflammation, vitamin K-dependent proteins, and procoagulant activity. Plasminogen activator inhibitor-1 clustered with the body mass factor, supporting the hypothesis that obesity is related to impaired fibrinolysis. Fibrinogen clustered with the inflammation summary factor rather than procoagulant activity, supporting the position that fibrinogen principally reflects underlying inflammation rather than procoagulant potential. The authors conclude that should hemostatic variables be shown to contribute to IRS-related cardiovascular disease, apart from plasminogen activator inhibitor-1, they may do so independently of the established metabolic abnormalities.

}, keywords = {Aged, Aged, 80 and over, Antigens, Blood Coagulation, Cardiovascular Diseases, Cluster Analysis, Factor Analysis, Statistical, Factor VII, Female, Fibrinogen, Fibrinolysis, Humans, Inflammation, Insulin Resistance, Male, Middle Aged, Plasminogen Activator Inhibitor 1, Risk Factors}, issn = {0002-9262}, doi = {10.1093/aje/152.10.897}, author = {Sakkinen, P A and Wahl, P and Cushman, M and Lewis, M R and Tracy, R P} } @article {628, title = {Association between physical activity and markers of inflammation in a healthy elderly population.}, journal = {Am J Epidemiol}, volume = {153}, year = {2001}, month = {2001 Feb 01}, pages = {242-50}, abstract = {

Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19\%, 6\%, 4\%, and 3\% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.

}, keywords = {Aged, Analysis of Variance, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Factor VIII, Female, Fibrinogen, Humans, Inflammation, Leukocyte Count, Male, Physical Exertion, Sex Factors, Smoking}, issn = {0002-9262}, doi = {10.1093/aje/153.3.242}, author = {Geffken, D F and Cushman, M and Burke, G L and Polak, J F and Sakkinen, P A and Tracy, R P} }