Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study.

OBJECTIVES: Our aim was to determine the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function. BACKGROUND: NA raises high-density lipoprotein cholesterol (HDL-C) and reduces low-density lipoprotein cholesterol and is widely used as an adjunct to statin therapy in patients with coronary artery disease. Although changes in plasma lipoproteins suggest potential benefit, there is limited evidence of the effects of NA on disease progression when added to contemporary statin treatment. METHODS: We performed a double-blind, randomized, placebo-controlled study of 2 g daily modified-release NA added to statin therapy in 71 patients with low HDL-C (<40 mg/dl) and either: 1) type 2 diabetes with coronary heart disease; or 2) carotid/peripheral atherosclerosis. The primary end point was the change in carotid artery wall area, quantified by magnetic resonance imaging, after 1 year. RESULTS: NA increased HDL-C by 23% and decreased low-density lipoprotein cholesterol by 19%. At 12 months, NA significantly reduced carotid wall area compared with placebo (adjusted treatment difference: -1.64 mm(2) [95% confidence interval: -3.12 to -0.16]; p = 0.03). Mean change in carotid wall area was -1.1 +/- 2.6 mm(2) for NA versus +1.2 +/- 3.0 mm(2) for placebo. In both the treatment and placebo groups, larger plaques were more prone to changes in size (r = 0.4, p = 0.04 for placebo, and r = -0.5, p = 0.02 for NA). CONCLUSIONS: In statin-treated patients with low HDL-C, high-dose modified-release NA, compared with placebo, significantly reduces carotid atherosclerosis within 12 months. (Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function; NCT00232531).

Reproducibility and accuracy of automated measurement for dynamic arterial lumen area by cardiovascular magnetic resonance.

Bright blood cine images acquired using magnetic resonance imaging contain simple contrast that is tractable to automated analysis, which can be used to derive a measure of arterial compliance that is known to correlate with disease severity. The purpose of this work was to evaluate whether automated methods could be used reliably on a clinically relevant population, and to assess the precision of these measurements so that it could be compared with expert manual assessment. In this paper we apply an algorithm similar to that used by Krug et al., and the exact processing steps are described in detail to allowing easy reproduction of our methods. Phantoms of different sizes have been assessed and the MRI measurements are found to correlate well (r = 0.9998) with physical measurement. Reproducibility assessment was performed on 33 CAD subjects in three anatomical locations along the aorta. Six normal volunteers and ten patients with more severe aortic plaques were investigated to assess reproducibility and sensitivity to pathological changes, respectively. The performance was also assessed on carotid vessels in 40 patients with known arterial plaques. In the human aorta the method is found to be robust (failing in only 7% of cases, all due to clear errors with image acquisition), and to be quantifiably consistent with expert clinical measurement, but showing smaller errors than that approach [<1.21% (5.62 mm(2)) manual vs. <0.58% (2.71 mm(2)) automated, for the aortic area] and with reduced bias, and operated correctly in advanced disease. We have proved over a large number of subjects the superiority of this automated method for evaluating dynamic area changes over the Gold-standard manual approach.