LIPOPROTEIN (A), HOMOCYSTEINE, AND HYPERCOAGULABLE STATES IN YOUNG MEN WITH PREMATURE PERIPHERAL ATHEROSCLEROSIS - A PROSPECTIVE, CONTROLLED ANALYSIS

Purpose: Elevated lipoprotein (a) (Lp[a]) lipoprotein, total homocyste ine, and hypercoagulable states (HCS) have all been implicated as risk factors for premature-onset atherosclerosis. This study was performed to determine the prevalence of these abnormalities in young men with chronic lower extremity ischemia (peripheral vascular disease [PVD]) a nd to determine their relative strengths as risk factors for premature I peripheral atherosclerosis. Methods: We analyzed 50 young white men (age 45 years or younger at onset of symptoms) and compared them with 45 age-matched white male control subjects. Results: Atherosclerotic risk factors were similar in both groups. The mean (+/- SEM) Lp(a) lip oprotein level was 36 +/- 6 mg/dl among the study patients, compared w ith 14 +/- 2 mg/dl among control subjects (p = 0.02, Mann-Whitney). Tw enty (40%) study patients and seven (16%) control subjects had Lp(a) L ipoprotein levels of 30 mg/dl or greater (atherosclerotic risk thresho ld) (p = 0.01, odds ratio = 3.62, confidence interval (CI) 1.4 to 9.5) . Positive HCS panels (antiphospholipid antibodies or deficiencies in antithrombin III, protein C, or protein S) were nearly twice as preval ent in study patients (n = 15, 30%) as in controls (n = 8, 18%), but t his difference did not achieve statistical significance. The mean tota l plasma homocysteine level among the study patients was 15.9 +/- 0.9 mu mol/L, which was not significantly different from the mean control value of 14.7 +/- 0.7 mu mol/L. Lp(a) lipoprotein was related to risk of premature PVD through a linear logistic relationship (p = 0.003, od ds ratio per each 1 mg/dl Lp(a) change was 1.03, CI 1.0 to 1.1). Multi variate analysis with stepwise logistic regression selected two variab les: Lp(a) lipoprotein greater than or equal to 30 mg/dl (p = 0.01, od ds ratio = 3.6, CI 1.3 to 9.9) and family history (p = 0.07, odds rati o = 2.2, CI 0.9 to 5.3). Tests of interaction demonstrated no effect b etween Lp(a) lipoprotein, HCS, and homocysteine. Conclusions: Lp(a) li poprotein of 30 mg/dl or greater is an independent risk factor for pre mature peripheral atherosclerosis in men. None of the other examined v ariables exhibited a significant association with premature PVD.