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Factor VII, cholesterol, and triglycerides. The CARDIA Study. Coronary Artery Risk Development in Young Adults Study
D Green1, M A Chamberlain, K J Ruth
1Department of Medicine, Northwestern University Medical School, Chicago, III, USA.
Insights
Elevated factor VII coagulant activity (VIIc) correlates with higher cholesterol and triglycerides, indicating an increase in the clotting factor itself. This association persists over time and across diverse populations.
Area of Science:
- Cardiovascular Research
- Hematology
- Epidemiology
Background:
- Cross-sectional studies link factor VII coagulant activity (VIIc) to cardiovascular risk factors like high cholesterol and triglycerides.
- The relationship between changing VIIc levels and evolving risk factors over time requires further investigation.
Purpose of the Study:
- To determine if changes in factor VII coagulant activity (VIIc) parallel changes in coronary risk factors over a 2-year period.
- To investigate whether elevated VIIc in individuals with high lipid levels is due to factor activation or increased factor VII concentration.
Main Methods:
- Analysis of data from 1514 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA).
- Examination of cross-sectional correlations and 2-year changes in VIIc, total cholesterol (TC), and triglycerides (TG).
- Measurement of factor VII antigen (VIIag) in a subsample to differentiate between VIIc activation and concentration.
Main Results:
- VIIc positively correlated with TC and TG across most race/sex groups.
- Changes in VIIc over 2 years were positively associated with changes in TC and TG.
- Factor VII antigen (VIIag) correlated strongly with VIIc, and lipid levels correlated with both VIIc and VIIag, suggesting increased factor VII concentration.
Conclusions:
- Elevated factor VII coagulant activity (VIIc) associated with higher lipid levels represents a true increase in factor VII concentration.
- This association is observed in both black and white individuals, across sexes, and persists over time.
- Findings suggest that increased factor VII concentration is a component of the relationship between lipids and coagulation.
Abstract:
Cross-sectional studies have shown that factor VII coagulant activity (VIIc) is positively associated with plasma total cholesterol (TC), LDL cholesterol, and triglycerides (TG) as well as body mass index (BMI) and diastolic blood pressure. To determine whether changes in VIIc parallel changes in coronary risk factors over a period of 2 years, we examined data from 1514 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA), an ongoing investigation of lifestyles and evolution of cardiovascular risk factors. Subjects were 23 to 35 years old at the year 5 examination. Cross-sectional analyses at these examinations showed that VIIc was positively correlated (P < .001) with TC and TG in all race/sex groups except for TC in black women at the year 5 examination. Changes in VIIc over the 2-year period were correlated positively with changes in TC in all except black men and TG in all groups; the association of VIIc change with change in TC and TG was reduced only slightly with adjustment for age and BMI at year 5 and 2-year change in BMI. To determine whether the higher levels of VIIc in subjects with higher lipid values were due to activation of the factor or to an increase in the concentration of the factor VII clotting protein, we measured factor VII antigen (VIIag) in a randomly selected subsample of 223 subjects at the year 7 examination. In all sex/race groups, VIIag correlated with VIIc (r = .69 to 0.81). After adjustment for sex and race, the partial correlation coefficient between TG and VIIc was .28 (P = .0001); between TG and VIIag, .35 (P = .0001); between TC and VIIc, .39 (P = .0001); and between TC and VIIag, 0.43 (P = .0001). No associations were observed between lipid levels and the ratio of VIIc to VIIag. We conclude that the raised VIIc with higher lipid levels occurs in blacks as well as whites, in men and women, persists over time, and represents a true increase in the plasma concentration of this clotting factor.