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E M Macy

Publications and source records attributed to E M Macy.

7 recordsLinked to original sources
PubMed1999

Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology.

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's biovariability data may be useful in interpreting simple statistics, and in designing multivariate models.

Adult↗
PubMed1999

Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.

Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group.

Age Factors↗
PubMed1998

Variability in plasma prothrombin concentration: implications for use in epidemiology.

Recent evidence suggests a major role for prothrombin as a risk factor for thrombosis. However, estimating prothrombin levels from a deficient plasma-based clotting assay (factor IIc) is expensive and technically difficult in the setting of population-based research. We report the development of an enzyme-linked immunosorbent assay (ELISA) for prothrombin using purified antigen and polyclonal anti-prethrombin-1 IgG. Three different quality control plasmas had coefficients of variation (CV) of 6.5%, 4.9%, and 4.8%. Analytical recovery averaged 103.8%. Results from the ELISA correlated well with factor IIc results (r=0.75). The 5th-95th percentile range for healthy men (n=10) and women (n=16) was 97.7 pg/ml to 161.8 microg/ml. The assay exhibited no significant cross-reactivity with other vitamin-K-dependent proteins. Prothrombin showed no diurnal variation. In a study of biovariability the analytical variability, CV(A), was 3.1%; the within-subject variability, CV(I), was 7.3%; the between-subject variability, CV(G), was 14.5%. The critical difference for sequential values (i.e. the smallest percentage change unlikely to be due to CV(A) or CV(I)) significant at P=0.05 was 21.9%. The index of individuality, CV(I)/CV(G), was 0.50. On the basis of the overall biovariability data, primarily the index of individuality, prothrombin as measured in our ELISA is well suited for applications in population-based research.

Adult↗
PubMed1997

Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications.

We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci 1989;27:409-37)], the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P < or =0.05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detecting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoint, the usefulness of CRP in longitudinal studies is suggested by the small index of individuality and by observations that (a) short-term fluctuations were infrequent, (b) all data stayed within the reference interval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.

Adolescent↗
PubMed1993

Sample preparation for plasma measurement of plasminogen activator inhibitor-1 antigen in large population studies.

Plasminogen activator inhibitor-1 is important in regulating fibrinolysis and may be an important cardiovascular risk factor. Because of this, there is increased interest in performing plasminogen activator inhibitor-1 assays in large epidemiologic studies. Our aim in this study was to determine the simplest blood collection methods that yield accurate results with our plasminogen activator inhibitor-1 antigen assay. Our results indicate that the following issues are important: (1) since there is a large circadian variation in plasminogen activator inhibitor-1 plasma levels, a target time frame must be established; (2) commercially available citrate collection tubes are adequate, if sample processing is rapid; (3) careful venipuncture is necessary, with freely flowing collection; hemolysis must be avoided; and (4) centrifugation of at least 30,000 g.min is required to avoid platelet contamination.

Blood Specimen Collection↗
PubMed1981

Analysis of human anti-diphtheria antibodies by isoelectric focusing: evidence for restricted clonal heterogeneity of anti-fragment A antibodies.

The in vivo human humoral response to diphtheria toxoid-tetanus toxoid booster immunization was studied by isoelectric focusing analysis of sera obtained after immunization. The anti-diphtheria toxoid (immunoglobulin G [IgG]-Dip), anti-fragment A (IgG-Frag A), and anti-tetanus toxoid antibodies from 20 donors post-booster immunization were focused by using agarose isoelectric focusing and visualized by development with radiolabeled antigens. The quantities of the IgG-Dip and IgG-Frag A antibodies correlated with the number of bands seen on the isoelectric focusing pattern in that more bands were found in the spectrotypes of donors with high serum levels of antibody. No difference was apparent in the antibody spectrotypes obtained from sera of donors at successive times post-booster immunization. Individual heterogeneity of the different donors' spectrotypes was often found for IgG-Frag A antibodies, but a close comparison of several different donors revealed antibodies with the same spectrotype patterns. Thus, individual clones of antibody were revealed in humans after in vivo immunization, particularly when antibodies against antigens of restricted epitope size were analyzed. Additionally, the sharing of certain antibody spectrotypes among several individuals raised the possibility that certain antibody clones may be preferentially expressed in the human population.

Antibody Specificity↗