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 homocysteine, 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]) and to determine their relative strengths as risk factors for premature 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) lipoprotein level was 36±6 mg/dl among the study patients, compared with 14±2 mg/dl among control subjects ( p=0.02, Mann-Whitney). Twenty (40%) study patients and seven (16%) control subjects had Lp(a) lipoprotein levels of 30 mg/dl or greater (atherosclerotic risk threshold) ( 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 prevalent in study patients (n=15,30%) as in controls (n=8,18%), but this difference did not achieve statistical significance. The mean total plasma homocysteine level among the study patients was 15.9±0.9 μmol/L, which was not significantly different from the mean control value of 14.7±0.7 μmol/L. Lp(a) lipoprotein was related to risk of premature PVD through a linear logistic relationship ( p=0.003, odds ratio per each 1 mg/dl Lp(a) change was 1.03, CI 1.0 to 1.1). Multivariate analysis with stepwise logistic regression selected two variables: Lp(a) lipoprotein≥30 mg/dl ( p=0.01, odds ratio=3.6, CI 1.3 to 9.9) and family history ( p=0.07, odds ratio=2,2, CI 0.9 to 5.3). Tests of interaction demonstrated no effect between Lp(a) lipoprotein, HCS, and homocysteine. Conclusions: Lp(a) lipoprotein of 30 mg/dl or greater is an independent risk factor for premature peripheral atherosclerosis in men. None of the other examined variables exhibited a significant association with premature PVD.