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Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

ABSTRACT: Background:Lipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification. Methods:We recruited 214 patients with CAVS from Montreal and 174 patients with CAVS and 108 controls from Québec City, Canada. In a second group of individuals with high (?75 nmol/L, n = 27) or low (<75 nmol/L, n = 28) Lp(a) levels, 18F-sodium fluoride positron emission tomography/computed tomography was performed to determine the difference in mean tissue-to-background ratio (TBR) of the aortic valve. Results:Patients with CAVS had 62.0% higher Lp(a) (median = 28.7, interquartile range [8.2-116.6] vs 10.9 [3.6-28.8] nmol/L, P < 0.0001), 50% higher OxPL-apolipoprotein-B (2.2 [1.3-6.0] vs 1.1 [0.7-2.6] nmol/L, P < 0.0001), and 69.9% higher OxPL-apolipoprotein(a) (7.3 [1.8-28.4] vs 2.2 [0.8-8.4] nmol/L, P < 0.0001) levels compared with individuals without CAVS (all P < 0.0001). Individuals without CAVS but elevated Lp(a) had 40% higher mean TBR compared with individuals with low Lp(a) levels (mean TBR = 1.25 ± 0.23 vs 1.15 ± 0.11, P = 0.02). Conclusions:Elevated Lp(a) and OxPL levels are associated with prevalent CAVS in patients studied in an echocardiography laboratory setting. In individuals with elevated Lp(a), evidence of aortic valve microcalcification by 18F-sodium fluoride positron emission tomography/computed tomography is present before the development of clinically manifested CAVS.

SUBMITTER: Despres AA

PROVIDER: S-EPMC7063623 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

Després Audrey-Anne AA Perrot Nicolas N Poulin Anthony A Tastet Lionel L Shen Mylène M Chen Hao Yu HY Bourgeois Raphaëlle R Trottier Mikaël M Tessier Michel M Guimond Jean J Nadeau Maxime M Engert James C JC Thériault Sébastien S Bossé Yohan Y Witztum Joseph L JL Couture Patrick P Mathieu Patrick P Dweck Marc R MR Tsimikas Sotirios S Thanassoulis George G Pibarot Philippe P Clavel Marie-Annick MA Arsenault Benoit J BJ

CJC open 20190412 3

<h4>Background</h4>Lipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcal ...[more]

PMID: 32159096

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Project description:Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and ectopic calcification. There is growing evidence that vascular calcification is associated with inflammatory status and is enhanced by inflammatory cytokines. Since PXE has never been considered as an inflammatory condition, no incidence of chronic inflammation leading to calcification in PXE has been reported and should be investigated. In atherosclerosis and aortic stenosis, positron emission tomography combined with computed tomographic (PET-CT) imaging has demonstrated a correlation between inflammation and calcification. The purpose of this study was to assess skin/artery inflammation and calcification in PXE patients. Methods: 18F-FluroDeoxyGlucose (18F-FDG) and 18F-Sodium Fluoride (18F-NaF) PET-CT, CT-imaging and Pulse wave velocity (PWV) were used to determine skin/vascular inflammation, tissue calcification, arterial calcium score (CS) and stiffness, respectively. In addition, inorganic pyrophosphate, high-sensitive C-reactive protein and cytokines plasma levels were monitored. In 23 PXE patients, assessment of inflammation revealed significant 18F-FDG uptake in diseased skin areas contrary to normal regions, and exclusively in the proximal aorta contrary to the popliteal arteries. There was no correlation between 18F-FDG uptake and PWV in the aortic wall. Assessment of calcification demonstrated significant 18F-NaF uptake in diseased skin regions and in the proximal aorta and femoral arteries. 18F-NaF wall uptake correlated with CS in the femoral arteries, and aortic wall PWV. Multivariate analysis indicated that aortic wall 18F-NaF uptake is associated with diastolic blood pressure. There was no significant correlation between 18F-FDG and 18F-NaF uptake in any of the artery walls. In the present cross-sectional study, inflammation and calcification were not correlated. PXE would appear to more closely resemble a chronic disease model of ectopic calcification than an inflammatory condition. To assess early ectopic calcification in PXE patients, 18F-NaF-PET-CT may be more relevant than CT imaging. It potentially constitutes a biomarker for disease-modifying anti-calcifying drug assessment in PXE.

Project description:BackgroundRespiratory motion correction is of importance in studies of coronary plaques employing 18 F-NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test-retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four-dimensional cine-computed tomography (CT) by an expert observer.PurposeTo investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of 18 F-NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine-CT images.MethodsThis study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using 18 F-sodium fluoride (18 F-NaF). All patients underwent a 5-s cine-CT (4D-CT), a coronary CT angiography (CTA), and 18 F-NaF PET. The 4D-CT and PET scan were reconstructed into 10 phases. Respiratory motion was estimated for the non-contrast visible coronary plaques using diffeomorphic registrations (PET) and compared to respiratory motion observed on 4D-CT. We report the PET motion vector fields obtained in the three principal axes in addition to the 3D motion. Statistical differences were examined using paired t-tests. Signal-to-noise ratios (SNR) are reported for the single-phase images (end-expiratory phase) and for the motion-corrected image-series (employing the motion vector fields extracted during the diffeomorphic registrations).ResultsIn total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT = 2.5 ± 1.5 mm, PET = 2.4 ± 3.2 mm; Y direction: 4D CT = 2.3 ± 1.9 mm, PET = 0.7 ± 2.9 mm, 3D motion: 4D CT = 6.6 ± 3.1 mm, PET = 5.7 ± 2.6 mm, all p ≥ 0.05). Significant differences in respiratory motion were observed in the systems' Z direction: 4D CT = 4.9 ± 3.4 mm, PET = 2.3 ± 3.2 mm, p = 0.04. Significantly improved SNR is reported for the motion corrected images compared to the end-expiratory phase images (end-expiratory phase = 6.8±4.8, motion corrected = 12.2±4.5, p = 0.001).ConclusionSimilar respiratory motion was observed in two directions and 3D for coronary plaques on 4D CT as detected by automatic respiratory motion correction of coronary PET using FusionQuant. The respiratory motion correction technique significantly improved the SNR in the images.

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Dataset Information

Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

Publications

Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

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