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Lipoprotein (a), homocysteine, and hypercoagulable states in young men with premature peripheral atherosclerosis: a
R J Valentine1, H S Kaplan, R Green
1Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Insights
Elevated lipoprotein (a) (Lp[a]) is a significant risk factor for premature peripheral artery disease in men. Levels of 30 mg/dl or greater strongly indicate this risk, independent of other factors.
Area of Science:
- Cardiovascular Medicine
- Genetics and Genomics
- Biochemistry
Background:
- Premature atherosclerosis, particularly peripheral vascular disease (PVD), poses a significant health risk.
- Elevated lipoprotein (a) (Lp[a]), total homocysteine, and hypercoagulable states (HCS) are implicated in atherosclerosis development.
Purpose of the Study:
- To determine the prevalence of Lp[a], homocysteine, and HCS abnormalities in young men with chronic lower extremity PVD.
- To assess the relative strengths of these factors as predictors of premature peripheral atherosclerosis.
Main Methods:
- A case-control study involving 50 young men (≤45 years) with PVD and 45 age-matched male controls.
- Analysis of Lp[a] lipoprotein levels, total plasma homocysteine, and HCS panels (antiphospholipid antibodies, antithrombin III, protein C, protein S deficiencies).
Main Results:
- Study patients had significantly higher mean Lp[a] levels (36 vs. 14 mg/dl) and a greater proportion exceeding the risk threshold of 30 mg/dl (40% vs. 16%).
- Lp[a] lipoprotein level ≥30 mg/dl was identified as an independent risk factor for premature PVD (odds ratio = 3.6).
- No significant differences were found in total homocysteine levels; HCS prevalence showed a non-significant trend towards higher rates in PVD patients.
Conclusions:
- Elevated Lp[a] (≥30 mg/dl) is a significant and independent risk factor for premature peripheral atherosclerosis in men.
- Other investigated factors, including homocysteine and HCS, did not show a statistically significant association with premature PVD in this cohort.
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 (aged 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 mumol/L, which was not significantly different from the mean control value of 14.7 +/- 0.7 mumol/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 > or = 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.