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Atherosclerosis and folic acid supplementation trial in chronic renal failure: baseline results
Sophia Zoungas1, Pauline Branley, Peter G Kerr
1Department of Vascular Sciences and Medicine, Monash University, Dandenong Hospital, Dandenong, Victoria, Australia. sophia.zoungas@med.monash.edu.au
Insights
Patients with chronic renal failure (CRF) show accelerated arterial aging, with higher carotid intima-medial thickness (IMT) and impaired arterial function compared to healthy individuals. This study investigates folic acid
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Vascular Biology
Background:
- Chronic renal failure (CRF) is associated with increased cardiovascular risk.
- Atherosclerosis progression and cardiovascular events are concerns in CRF patients.
- The ASFAST trial investigates high-dose folic acid supplementation in CRF.
Purpose of the Study:
- To compare arterial structure and function in CRF patients versus healthy controls.
- To establish baseline measurements for the ASFAST trial.
- To assess arterial aging markers in CRF.
Main Methods:
- Recruitment of 315 CRF patients and 213 healthy controls.
- Measurement of carotid intima-medial thickness (IMT) via ultrasound.
- Assessment of systemic arterial compliance (SAC), augmentation index (AI(x)), and pulse wave velocity (PWV) using applanation tonometry.
- Assay of lipids, total homocysteine (tHcy), red cell folate, cobalamin, and fibrinogen in CRF patients.
Main Results:
- CRF patients exhibited significantly increased mean IMT compared to controls (0.86 vs 0.68 mm).
- CRF patients showed significantly lower SAC and higher PWV (a-f) and AI(x), indicating impaired arterial function.
- 97% of CRF patients had elevated total homocysteine (tHcy) levels (mean 27.3 micromol/L).
- Higher tHcy levels correlated with lower SAC and higher PWV (a-f) in CRF patients.
Conclusions:
- CRF patients demonstrate accelerated arterial aging, equivalent to a 10-15 year increase in vascular age.
- Significant increases in carotid IMT, PWV (a-f), and central pressure augmentation were observed in CRF.
- The ASFAST trial will evaluate the effect of folic acid on cardiovascular outcomes and arterial function in CRF.
Background:
Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is a randomized placebo controlled trial assessing whether high-dose folic acid can reduce cardiovascular events and atherosclerosis progression in patients with chronic renal failure (CRF). Here we report the baseline results and compare indices of arterial structure (carotid intima-medial thickness (IMT)) and function (systemic arterial compliance (SAC)), pressure augmentation index (AI(x)) and pulse wave velocity (PWV a-f and PWV f-d)) to age- and sex-matched controls.
Methods:
Three hundred and fifteen subjects with CRF (serum creatinine > or = 0.40 mmol/L) aged 24-79 years (mean +/- SD: 56.6 +/- 13.6 years) and 213 healthy controls (58.2 +/- 10.2 years) were studied. Fasting blood samples were assayed for lipids (both groups), total homocysteine (tHcy), red cell folate, cobalamin and fibrinogen (CRF group). Ultrasound B mode measurements were used to determine mean carotid IMT and applanation tonometry techniques to determine SAC, AI(x), PWV (a-f), PWV (f-d) and central pressures.
Results:
Ninety-six per cent of the CRF group had at least one of: hypertension, hypercholesterolaemia, diabetes or smoking; 35% had established cardiovascular disease. The mean IMT was greater in CRF patients than in controls (0.86 +/- 0.19 vs 0.68 +/- 0.11 mm, P < 0.001). The SAC was significantly lower, and PWV (a-f) and AI(x) significantly higher. The tHcy was increased in 97% of the CRF group (27.3 +/- 2.9 micromol/L (normal < 13)). Total homocysteine did not correlate with IMT or any other measure of arterial function. However, those in the upper quantile of tHcy (> or =25 micromol/L) did have higher PWV (a-f) and lower SAC than those in the lower quantile.
Conclusions:
Compared to normals, patients with CRF exhibited a 10-15-year shift to the right in age-related increases in carotid IMT and PWV (a-f), and significantly increased central pressure augmentation. This 5-year study is examining the impact of high-dose folic acid therapy on cardiovascular end-points, IMT progression and arterial function in CRF.
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