A prospective evaluation of atherosclerotic risk factors and hypercoagulability in young adults with premature lower extremity atherosclerosis.

PURPOSE

Fifty-one consecutive patients with premature lower extremity atherosclerosis were prospectively evaluated for atherogenic risk factors and primary or acquired hypercoagulability, which might contribute to early ischemia and revascularization failure.

METHODS

Laboratory tests included plasma assays of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin antibodies, and (2) fibrinolytic activators and inhibitors at baseline and stimulated after 20 minutes of upper extremity venous occlusion.

RESULTS

Forty-six (90%) of these 51 patients had laboratory abnormalities. One or more NAC deficiencies were found in 15 (30%) patients and included antithrombin III (n = 5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2). Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1 (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%) patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies, especially protein C deficiency, were associated with acute ischemia (p < 0.01), prior vascular intervention (p < 0.01), an increasing number of total vascular procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05). Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20 patients suggested that 80% of NAC deficiencies were acquired, but abnormalities persisted in 66% of patients with elevated PAI-1 and in 93% of those with elevated Lp(a).

CONCLUSIONS

These data strongly support the hypothesis that the convergence of atherogenic risk factors and hypercoagulability play an important role in early ischemia and poor results reported for lower extremity vascular procedures in young adults.