Does Vascular Calcification Accelerate Inflammation?: A Substudy of the dal-PLAQUE Trial

OBJECTIVES: Atherosclerosis is an inflammatory condition with calcification apparent late in the disease process. The extent and progression of coronary calcification predict cardiovascular events. Relatively little is known about noncoronary vascular calcification. This study investigated noncoronary vascular calcification and its influence on changes in vascular inflammation.

METHODS:  A total of 130 participants in the dal-PLAQUE (Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging) study underwent fluorodeoxyglucose positron emission tomography/computed tomography at entry and at 6 months. Calcification of the ascending aorta, arch, carotid, and coronary arteries was quantified. Cardiovascular risk factors were related to arterial calcification. The influences of baseline calcification and drug therapy (dalcetrapib vs. placebo) on progression of calcification were determined. Finally, baseline calcification was related to changes in vascular inflammation.

RESULTS:  Age >65 years old was consistently associated with higher baseline calcium scores. Arch calcification trended to progress more in those with calcification at baseline (p = 0.055). There were no significant differences between progression of vascular calcification with dalcetrapib compared to that with placebo. Average carotid target-to-background ratio indexes declined over 6 months if carotid calcium was absent (single hottest slice [p = 0.037], mean of maximum target-to-background ratio [p = 0.010], and mean most diseased segment [p < 0.001]), but did not significantly change if calcification was present at baseline.

CONCLUSIONS:  Across multiple arterial regions, higher age is consistently associated with higher calcium scores. The presence of vascular calcification at baseline is associated with progressive calcification; in the carotid arteries, calcification appears to influence vascular inflammation. Dalcetrapib therapy did not affect vascular calcification.

COMPETENCY IN MEDICAL KNOWLEDGE: In several vascular territories, evidence of inflammation detected by serial [18F]FDG-PET/CT imaging appears to precede arterial calcification, and the intensity of [18F]FDG uptake is associated with the rate of progression of arterial calcification, but temporal relationships vary from one arterial region to another.

TRANSLATIONAL OUTLOOK: Longer-term studies are needed to explore the relationships among vascular inflammation, calcification, and clinical ischemic events. 


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