Effects of age and cardiovascular risk factors on (18)F-FDG PET/CT quantification of atherosclerosis in the aorta and peripheral arteries.

OBJECTIVE: To quantify fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the aorta and peripheral arteries and assess the variation of (18)F-FDG uptake with age and cardiovascular risk factors. METHODS: The subject population of this retrospective study comprises melanoma patients who underwent whole-body (18)F-FDG PET/CT scans. The patients' medical records were examined for cardiovascular risk factors and for a history of coronary artery disease or peripheral artery disease. Fluorine-18-FDG uptake in the peripheral arteries (iliac and femoral) and aorta was semi-quantified as a weighted-average mean standardized uptake value (wA-SUVmean), while background noise was accounted for by measuring mean venous blood pool SUV (V-SUVmean) in the superior vena cava. Atherosclerosis was semi-quantified by the tissue-to-background ratio (TBR) (wA-SUVmean divided by V-SUVmean). A regression model and t-test were used to evaluate the effect of age and location on the degree of atherosclerosis. To assess the effect of cardiovascular risk factors on atherosclerotic burden, the wA-SUVmean of patients with at least one of these risk factors was compared to that of patients without any risk factors. RESULTS: A total of 76 patients (46 men, 30 women; 22-91 years old) were included in this study. The average TBR of the aorta and peripheral arteries were 2.68 and 1.43, respectively, and increased with age in both locations. In regression analysis, the beta coefficients of age for TBR in the aorta and peripheral arteries were 0.55 (P<0.001) and 0.03 (P<0.001), respectively. In all age groups, the TBR of the aorta was significantly greater than that of the peripheral arteries. The Pearson correlation coefficients between the four age groups and the TBR of the aorta and peripheral arteries were 0.83 (P<0.001) and 0.75 (P<0.001), respectively. The wA-SUVmean of patients with cardiovascular risk factors was only significant (P<0.05) in the aorta. CONCLUSION: An increase in (18)F-FDG uptake was observed in the peripheral arteries and aorta with increasing age. Cardiovascular risk factors were significantly correlated with (18)F-FDG uptake in aorta. The early detection of atherosclerosis with (18)F-FDG PET may allow for the initiation of preventative interventions prior to the manifestation of significant structural abnormalities or symptoms of disease.

Models of aortic valve calcification.

Aortic valve stenosis is a complex inflammatory process, akin to arterial atherosclerosis, involving lymphocytic infiltrates, macrophages, foam cells, endothelial activation and dysfunction, increased cellularity and extracellular matrix deposition, and lipoprotein accumulation. A clonal population of aortic valve myofibroblasts spontaneously undergoes phenotypic transdifferentiation into osteoblast-like cells and forms calcific nodules in cell culture. Animal models complement these cell culture models by providing in vivo systems in which to study the complex molecular and cellular interactions that cause aortic valve disease in the native hemodynamic and biochemical environment. Whereas some species, such as swine, can develop spontaneous vascular and valvular atherosclerotic lesions, others, such as rabbits and mice, have not been shown to develop lesions naturally and require an inciting factor, such as hypercholesterolemia. In this article, we review the published cell culture and animal models available to study calcific aortic valve disease.

Correlates of valvular ossification in patients with aortic valve stenosis.

Valvular calcification may include a regulated process of active ossification; however, the determinants of ossification are unclear. The aim of this study was to identify subject and disease characteristics associated with valvular ossification among patients with calcified aortic valves. Medical records were reviewed for variables associated with aortic stenosis and skeletal bone in a series of 195 patients requiring aortic valve excision. Thirty patients had valvular bone on histopathology. Univariate analyses suggested that warfarin therapy (p= 0.004), African American race (p= 0.006), height (p= 0.03), and male sex (p= 0.07) were associated with greater odds of valvular ossification while diabetes was associated with lower odds (p= 0.07). Multivariate analysis demonstrated that warfarin use (OR 5.7; 95% CI: 1.5-21.3; p= 0.009) and African American race (OR 8.3; 95% CI: 1.8-39.0; p= 0.007) were strongly and independently associated with increased odds of valvular ossification. Valvular ossification was not associated with greater ossification of costochondral cartilage on chest radiography. Warfarin therapy and African American race were associated with increased risk of valvular ossification in patients with aortic stenosis. Future studies are needed to confirm this finding and determine if inhibition of matrix GLA protein by warfarin mediates this effect.

Noninvasive atherosclerosis imaging for predicting cardiovascular events and assessing therapeutic interventions.

Noninvasive assessment of atherosclerosis offers an opportunity to provide individual cardiovascular risk management and an opportunity to monitor the efficacy of therapy targeted toward atherosclerosis. The three imaging modalities that currently hold the most promise at the clinical and research levels are ultrasound for carotid intima-media thickness, computed tomography for coronary artery calcification, and magnetic resonance imaging for carotid and aortic plaque imaging. The following review describes the evidence that validates each technique as a surrogate marker of atherosclerosis, with an emphasis on cardiovascular events and the progression of disease. Both the particular strengths and limitations of each imaging modality are discussed.