Plasma homocysteine predicts progression of atherosclerosis

Abstract

MINI ABSTRACT: Three emerging risk factors potentially useful in predicting future cardiac events are electron-beam computed tomography (EBT), homocysteine(HCY), and C-reactive Protein (CRP). We evaluated a cohort of 133 serial asymptomatic patients, who underwent two consecutive EBT scans (8-84 months apart) and a comprehensive cardiac risk factor assessment, including measurements for lipids, ultrasensitive CRP and homocysteine. Individuals with elevated HCY (> or =12 micromol/L) demonstrated a mean increase in CC progression of 35% per year, while those with HCY <12 micromol/L (median) progressed at 17% per year (p = 0.0008). Patients with a level equal to or lower than the median value of CRP (0.8 mg/L) had a median yearly progression of 22%, compared to 21% for those with CRP value = 0.9-11 mg/L (p = ns). Presence of elevated HCY (>12 micromol/L) strongly and independently predicts progression of coronary plaque burden.

Background: Despite the availability of effective preventive therapies, coronary artery disease (CAD) remains the leading cause of morbidity and mortality. Use of traditional cardiovascular risk factors is imprecise and predicts less than one half of future cardiovascular events. Three 'emerging risk factors', as potential means of identifying subclinical atherosclerosis and predicting future cardiovascular events, are electron-beam computed tomography, homocysteine, and C-reactive protein. Given the evidence that HCY and CRP are involved in atherogenesis, we hypothesized that significant progression of EBT calcium score (a measure of atherosclerotic plaque burden) is associated with higher levels of these markers.

Methods: We evaluated 133 asymptomatic patients (100 men, 33 women; mean age was 61 +/- 9 years) who underwent previous EBT calcium score testing at Harbor-UCLA 8-80 months prior to enrollment (mean follow-up 20 months). Exclusion criteria included those with known or symptomatic CAD and chronic renal disease. During enrollment, we measured risk factors, serum HCY, serum lipids, ultrasensitive-CRP, and repeat EBT calcium scan. Statistical analysis was performed using probable Chi square method, and Student's t-test.

Results: Individuals with elevated HCY (> or =12 micromol/L) demonstrated a mean increase in CC progression of 35% per year, while those with HCY <12 micromol/L (median) progressed at 17% per year (p = 0.0008). Patients with a level equal to or lower than the median value of CRP (0.8 mg/L) had a median yearly progression of 22%, compared to 21% for those with CRP value = 0.9-11 mg/L (p = ns). Neither cholesterol values, body mass index, gender, age nor presence of individual risk factors predicted progression of coronary calcium.

Conclusion: Presence of elevated HCY (>12 micromol/L) strongly and independently predicts progression of coronary plaque burden.