Rationale and Objectives
Although studies have reported direct inhibition of inflammatory pathways with niacin, the effect of niacin on arterial wall inflammation remains unknown. We examined the effect of niacin on arterial 18 F-fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT).
Materials and Methods
Nine statin-treated patients with coronary disease were randomized to niacin 6000 mg/day or placebo. FDG-PET/CT and lipids were assessed at baseline and at 12 weeks. FDG was quantified in the aorta, right carotid artery, and left carotid artery as the target-to-background ratio (TBR) and target-to-background difference (TBD).
Results
Eight patients completed the study. No significant changes in FDG measured by aortic, left carotid, or right carotid TBR or TBD were seen in either group. Compared to baseline, niacin-treated subjects exhibited a significant 29% reduction in low-density lipoprotein cholesterol (LDL-C; 95% confidence interval [CI], −50% to 8%; P = .01) and a nonsignificant 29% reduction in LDL particle number (LDL-P; 95% CI, −58% to 0.2%; P = .07). A nonsignificant 11% increase in HDL-C (95% CI, −15% to 37%; P = .30) and 8% decrease in HDL-P (95% CI, −44% to 28%; P = .51) were observed with niacin treatment. In a pooled analysis, changes in LDL-P were positively correlated with FDG uptake in the aorta (TBR r = 0.66, P = .08; TBD r = 0.75, P = .03), left carotid (TBR r = 0.65, P = .08; TBD r = 0.74, P = .03), and right carotid (TBR r = 0.54, P = .17; TBD r = 0.61, P = .11).
Conclusions
In this pilot study, adding niacin to statin therapy did not affect arterial wall inflammation measured by FDG-PET/CT. However, an association between changes in arterial FDG uptake and LDL-P was observed. Larger studies are needed to definitively examine the effect of niacin on arterial wall inflammation.
Despite over 50 years of use for the management of dyslipidemia , the potential role of niacin in the prevention of atherothrombotic disease and its mechanism of action remain uncertain. In two large randomized trials, AIM-HIGH and HPS2-THRIVE , niacin failed to achieve an incremental benefit in cardiovascular risk reduction when added to an aggressive low-density lipoprotein (LDL)–lowering approach with statin therapy. Independent of its effects on circulating lipids, niacin has more recently been shown to directly inhibit inflammation through activation of the G-protein–coupled receptor GPR109A . Therefore, we sought to characterize the effects of niacin on arterial wall inflammation using 18 F-fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT), an emerging imaging surrogate measure of atherosclerotic risk .
A growing body of evidence from clinical studies supports the utility of FDG-PET/CT imaging for the noninvasive characterization of atherosclerosis . Cross-sectional analyses initially performed in cancer patients demonstrated a consistent positive association between arterial FDG signal and traditional atherosclerotic risk factors including age , hypertension , and body mass index and a higher prevalence of cardiovascular disease among patients with increased vascular FDG uptake . Case–control studies of patients with clinically manifested atherosclerotic disease demonstrated more avid FDG uptake in arteries harboring atherosclerotic plaques compared to unaffected vessels and greater FDG signal among culprit plaques causing stroke or acute coronary syndrome compared to clinically silent plaque. Most recently, a prospective cohort study demonstrated significant improvement in risk prediction of incident cardiovascular events with incorporation of aortic FDG uptake into a model of traditional risk factors . Large studies, such as the Progression and Early detection of Subclinical Atherosclerosis study targeting enrollment of 4000 adults, are underway to further evaluate the potential incremental prognostic value of arterial FDG uptake above and beyond classical cardiovascular risk factors .
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Materials and methods
Design and Subjects
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Study Treatment
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Lipids, Lipoproteins, and Metabolic Assessment
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FDG-PET/CT Imaging
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Statistical Analysis
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Results
Clinical Characteristics
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Lipids and Lipoproteins
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Table 1
Plasma Lipids and Lipoproteins
Placebo ( n = 3) Niacin ( n = 5) Baseline Posttreatment Baseline Posttreatment Total cholesterol (mg/dL) 150 (23) 150 (17) 164 (39) 132 (47) Triglycerides (mg/dL) 89 (31) 108 (55) 129 (43) 81 (28) HDL-C (mg/dL) 38 (2) 40 (4) 45 (5) 50 (12) LDL-C (mg/dL) 91 (13) 89 (24) 90 (40) 67 (40) ∗ LDL-P (nmol/L) 1403 (286) 1337 (305) 1315 (563) 948 (552) † HDL-P (μmol/L) 28 (6.3) 31 (2.9) 32 (3.2) 29 (7.4)
C, cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; P, particle number.
Differences between the two treatment groups were examined using the unpaired Student t test. No significant differences in posttreatment values were observed. Mean (standard deviation) are provided for placebo- and niacin-treated groups. The paired Student t test was performed for the comparison of the data before and after treatment for a given treatment group.
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FDG-PET/CT Imaging
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Table 2
Mean (Standard Deviation) of TBR and TBD in Placebo- and Niacin-Treated Groups
Vessel FDG Index Placebo Niacin Baseline 12 Weeks Change Baseline 12 Weeks Change Aorta TBR 1.28 (0.16) 1.23 (0.11) −0.05 (0.12) 1.33 (0.09) 1.32 (0.19) −0.02 (0.14) TBD 0.28 (0.13) 0.25 (0.09) −0.03 (0.11) 0.35 (0.08) 0.29 (0.15) −0.06 (0.13) Left carotid TBR 1.35 (0.10) 1.29 (0.03) −0.07 (0.12) 1.36 (0.11) 1.40 (0.28) 0.04 (0.19) TBD 0.36 (0.08) 0.32 (0.07) −0.05 (0.08) 0.37 (0.09) 0.37 (0.24) −0.01 (0.17) Right carotid TBR 1.29 (0.17) 1.22 (0.06) −0.07 (0.12) 1.23 (0.09) 1.28 (0.31) 0.05 (0.25) TBD 0.29 (0.14) 0.23 (0.05) −0.05 (0.10) 0.24 (0.07) 0.24 (0.28) 0.01 (0.22)
FDG, 18 F-fluorodeoxyglucose; TBD, target-to-background difference; TBR, target-to-background ratio.
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Table 3
Correlation Between Aortic, Left Carotid, and Right Carotid Indices of FDG Uptake
Vessel FDG Index_r__P_ Aorta versus left carotid TBR 0.90 <.01 TBD 0.87 <.01 Aorta versus right carotid TBR 0.92 <.01 TBD 0.86 <.01 Left versus right carotid TBR 0.90 <.01 TBD 0.82 .01
FDG, 18 F-fluorodeoxyglucose; TBD, target-to-background difference; TBR, target-to-background ratio.
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Discussion
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Acknowledgments
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Supplementary Data
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Supplementary Tables 1–4
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