Procoagulants and Subclinical Atherosclerosis in Young Adults: The CARDIA Study.

Elevated levels of procoagulants (FVII, FVIII, vWF) have been associated with cardiovascular disease, but whether they play a role in atherogenesis is unclear. Study of these factors in young adulthood, prior to clinically manifested disease, and years later when subclinical atherosclerosis has developed, might clarify these associations. The Coronary Artery Risk Development in Young Adults (CARDIA) Study provides an opportunity to examine this issue.

Assays of FVII, FVIII, and vWF were performed in 1255 participants ages 23-37 (Year 7,Y7) and repeated at ages 38-50 (Year 20,Y20). Coronary artery calcification (CAC) prevalence and mean intimal-medial thickness (IMT) in the common carotid (CC) and internal carotid (IC) were measured at Y20. Prospective (Y7 clotting factors, Y20 CAC & IMT) and cross-sectional (Y20 clotting factors, Y20 CAC & IMT) analyses were performed. We also grouped participants according to whether they had one or more procoagulants in the highest tertile at Y7, Y20, or both, and evaluated their associations with subclinical disease.

Y7 levels of procoagulants (%), mean(SD) were: FVII 76(18), FVIII 102(38), and vWF 108(47). At Y20, all had increased by 40% to 55%, and CAC>0 was present in 20% of participants. After adjustment for age, the prospective analyses showed a trend of progressively greater CC thickness from the lowest to the highest tertile of FVII activity in the total group (P=0.007) and in whites (P=0.002) and men (P=0.015). Associations of FVII with IC thickness (0.82 mm to 0.84 mm) and the prevalence of CAC (18.6% to 23%) were weaker (P-trend, 0.1-0.3). Higher FVIII levels were associated with greater IC thickness in the total group, in whites, and in women (highest vs lowest tertile, P<0.05 for each comparison). No associations were seen with vWF. Cross-sectional analyses confirmed the association between FVII and carotid thickening, most strongly with the CC (P=0.002). Most associations were attenuated by multivariable adjustment (BMI, smoking, education, blood pressure, cholesterol, & CRP). Participants with FVII values in the highest tertile at Y7, Y20, or both had a higher prevalence of CAC and greater carotid thickening than those with values in the lowest tertile (P<0.05). Such associations were not observed with FVIII or vWF.

FVII is a marker but not an independent risk factor for future atherosclerosis in young adults; FVIII is associated with IC thickening, and no associations were observed for vWF.

No relevant conflicts of interest to declare.