displays the characteristics of study participants according to gender-race groups at Y7. Black people were younger, had a higher BMI, fewer years of education, and more black people than white people were current smokers. Black people had higher mean systolic BP and more black women used antihypertensive medication. HDL cholesterol was lower in white men, but CRP was higher in black people than in white people. Mean fibrinogen was 3.32 g L−1, and was higher in the older members of the cohort (3.29 at age 24–28 and 3.44 at age 37–41). Over the course of 13 years, mean fibrinogen in the total group rose to 4.05 g L−1 (3.98 at age 37–41 and 4.24 at age 50–54). While fibrinogen was significantly higher in black people than in white people (P < 0.001), the magnitude of the increase (22%) was similar in all race/gender groups. Increases were also noted in CRP (median CRP, 1.05–1.12 µg mL−1) and BMI (26.5–29.4 kg m−2).
Characteristics of study participants according to gender-race group, the CARDIA Study, 1992–2006*
shows associations between Y7 fibrinogen tertiles and Y20 CAC. CAC was more prevalent among men than women and white than black men. After adjustment for age, gender and race, the association of elevated fibrinogen with greater incidence of CAC was highly significant for the total sample (P-trend < 0.001) and for all race/gender subgroups, and remained significant for the total group (P-trend = 0.047), although not for the subgroups, after further adjustment for field center, BMI, smoking, education, systolic blood pressure, diabetes, antihypertensive medication use, and total and HDL cholesterol levels. shows that associations between Y20 fibrinogen and Y20 CAC were significant for the total sample after age, gender and race adjustment (P-trend < 0.001), but not after multivariable adjustment.
Associations between (A) year 7 (baseline) and (B) year 20 fibrinogen and incidence of coronary artery calcium (CAC) at year 20; the CARDIA Study*
We also looked for associations between fibrinogen and intima-media thickness (IMT) of the common and internal carotid arteries. While Y7 fibrinogen in the total group was significantly associated with Y20 common and internal carotid IMT after age, gender and race adjustment (P < 0.001), significance was not retained after multivariable adjustment (P > 0.1). Similarly, Y20 fibrinogen in the total group was significantly associated with Y20 common and internal carotid IMT after age, gender and race adjustment (P < 0.001), but not after multivariable adjustment (P > 0.1). In a supplemental regression analysis that singly included potential covariates one at a time into the age-, gender- and race-adjusted model, BMI and smoking substantially reduced the fibrinogen coefficient, and the P-value for the fibrinogen coefficient was no longer statistically significant at the 0.05 level.
Next, we performed analyses to examine whether individuals with fibrinogen in the highest tertile at either Y7 or Y20 (Group 3), or both (Group 4) would have higher incidence of CAC compared with participants with fibrinogen levels in the lowest tertile at both Y7 and Y20 (Group 1, referent). In age, gender and race adjusted analyses, participants in Group 4 had the most CAC, followed by those in Group 3; those whose fibrinogen was in the lowest tertile at both time points (Group 1) had the lowest incidence of CAC (). The relationships between fibrinogen groups and age-adjusted incidence of CAC > 0 were consistent for each of the four race-gender groups. After further adjustment for other Y7 coronary risk factors, associations were only significant for Group 3 of the total sample and not significant for any subgroup (). A similar analysis examining carotid IMT showed that common and internal carotid IMT were greater in Group 4 than in Group 1 (P < 0.05) after adjustment for age, gender and race, but not after multivariable adjustment.
Fig. 2 Adjusted incidence of having coronary artery calcium at year 20 by change in fibrinogen tertile groups. (A) All results adjusted for age. (B) All results adjusted for field center, age, BMI, smoking, systolic BP, total and HDL cholesterol, and year 7 (more ...)
We employed a multiple imputation method to adjust for the potential bias caused by dropouts and missing data. The two sets of estimates (imputed and not-imputed) were consistent, with the direction and magnitude of the relationship between fibrinogen and incidence of CAC and CIMT persisting across most of the various sensitivity analyses (data not shown), thus providing assurance that our results were likely to be robust despite some loss of participants due to dropouts or missing data.