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Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients
1Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229.
Insights
High homocysteine levels are common in hyperlipidemia patients and independently predict atherosclerotic vascular disease. Folic acid and pyridoxine effectively lower homocysteine, reducing associated vascular risks.
Area of Science:
- Cardiovascular Medicine
- Clinical Chemistry
- Nutritional Science
Background:
- Hyperlipidemia is a known risk factor for atherosclerotic vascular disease (AVD).
- Elevated homocysteine levels are increasingly recognized as a potential contributor to AVD.
- The prevalence and independent association of homocysteinemia with AVD in hyperlipidemic patients require further investigation.
Purpose of the Study:
- To determine the prevalence of homocysteinemia in patients with hyperlipidemia.
- To assess if homocysteinemia is an independent predictor of atherosclerotic vascular disease.
- To evaluate the efficacy of folic acid and pyridoxine in treating elevated homocysteine levels.
Main Methods:
- Cross-sectional study of 482 patients referred for hyperlipidemia diagnosis and therapy.
- Measurement of plasma homocysteine and cystathionine levels.
- Logistic regression analysis to assess the independent association of homocysteine with AVD.
- Intervention with folic acid and pyridoxine in patients with high homocysteine.
Main Results:
- Homocysteinemia (homocysteine >= 16.2 mumol/L) was present in 3.7% of patients.
- Patients with high homocysteine had a significantly higher prevalence of AVD (72% vs. 44%, p=0.02).
- Homocysteine was an independent predictor of AVD (p=0.007), with a 2.8-fold higher risk in the top quintile.
- Folic acid and pyridoxine therapy normalized homocysteine levels in 10 patients (median decrease from 18 to 11 mumol/L, p=0.001).
Conclusions:
- Homocysteinemia is prevalent in hyperlipidemic patients and is an independent risk factor for atherosclerotic vascular disease.
- Early detection and treatment of high homocysteine may mitigate cardiovascular risk.
- Folic acid and pyridoxine supplementation are effective in reducing homocysteine levels.
Abstract:
In 482 patients sequentially referred for diagnosis and therapy of hyperlipidemia, our specific aim was to determine the prevalence of homocysteinemia, to assess whether it was independently associated with atherosclerotic vascular disease, and to determine how effectively high homocysteine could be treated with folic acid and pyridoxine. Of the 482 patients, 18 (3.7%) had high homocysteine (> or = 16.2 mumol/L, median = 19), 31 had high cystathionine (> or = 342 nmol/L) with normal homocysteine (median = 12), and 433 had normal cystathionine and homocysteine (median = 9). Of the 18 patients with high homocysteine, 13 (72%) had atherosclerotic vascular disease, much higher than the 44% (192 of 433 patients) with normal homocysteine (chi-square = 5.4, p = 0.02). In the 18 kindreds with a homocysteinemic proband, 14 (78%) had > or = 1 first-degree relatives with atherosclerotic vascular disease before age 65, compared with 50% (215 of 433) of the families where the proband had normal homocysteine (chi-square = 5.5, p = 0.02). In the 482 patients already at high risk for atherosclerotic vascular disease by virtue of hyperlipidemia, when assessed by logistic regression, homocysteine was an independent positive predictor of atherosclerotic vascular disease (p = 0.007); relative risk for atherosclerotic events was 2.8 times higher (p = 0.0004) in patients with top (> or = 11.4 mumol/L) than with bottom (< 6.9 mumol/L) quintile homocysteine. After 15 weeks of folic acid (5 mg/day) and pyridoxine (100 mg/day) therapy in 10 patients with high homocysteine, median homocysteine normalized, decreasing from 18 to 11 mumol/L (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)