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Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study
M Cushman1, R N Lemaitre, L H Kuller
1Department of Medicine and Pathology, University of Vermont, Colchester, VT, USA.
Insights
Plasma markers D-dimer and plasmin-antiplasmin complex (PAP) predict arterial thrombosis in healthy elderly individuals over 65. These fibrinolysis markers identify high risk for myocardial infarction and coronary death, independent of other factors.
Area of Science:
- Gerontology
- Cardiovascular Medicine
- Hematology
Background:
- Coagulation factors are known predictors of arterial thrombosis in general populations.
- Limited research exists on these markers' predictive value for arterial thrombosis specifically in elderly individuals.
- Fibrinolysis markers, including PAI-1, D-dimer, and PAP, are implicated in thrombotic processes.
Purpose of the Study:
- To investigate the predictive value of plasma fibrinolysis markers for arterial thrombosis in healthy elderly individuals (age >/=65).
- To assess whether D-dimer, PAI-1, and PAP levels predict myocardial infarction, angina, or coronary death in this demographic.
- To determine if these associations are independent of other risk factors like inflammation markers.
Main Methods:
- A nested case-control study design was employed within the Cardiovascular Health Study cohort.
- Participants included 5201 men and women aged 65 and older, enrolled between 1989-1990.
- Cases (n=146) developed arterial thrombotic events, while controls were matched for sex, follow-up duration, and baseline subclinical disease.
Main Results:
- Elevated levels of D-dimer and PAP, but not PAI-1, were independently associated with an increased risk of myocardial infarction or coronary death.
- The relative risk for D-dimer above the median was 2.5, and for PAP above the median was 3.1.
- These associations remained significant and independent of C-reactive protein and fibrinogen levels, and showed no sex differences.
Conclusions:
- Plasma D-dimer and PAP levels are significant predictors of future myocardial infarction and coronary death in elderly men and women.
- PAI-1 did not demonstrate predictive value for arterial thrombosis in this age group.
- These fibrinolysis markers play a crucial role in identifying elderly individuals at high risk for arterial disease.
Abstract:
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.