Abstract Background Statins can regress coronary atheroma and lower clinical events. Although pre-clinical studies suggest procalcific effects of statins in vitro, it remains unclear if statins can ...modulate coronary atheroma calcification in vivo. Objectives This study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy. Methods In a post-hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, serial changes in coronary percent atheroma volume (PAV) and CaI were measured across matched coronary segments in patients with coronary artery disease. Results Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) associated with PAV regression from baseline (−0.6 ± 0.1%; p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin; p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median interquartile range HIST, +0.044 0.0–0.12; LIST, +0.038 0.0–0.11; no-statin, +0.020 0.0–0.10; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and C-reactive protein, in either of the HIST groups or the no-statin group. Conclusions Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque regression.
Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder that elevates low-density lipoprotein cholesterol and increases the risk of premature atherosclerotic cardiovascular disease ...(ASCVD). However, despite their atherogenic lipid profiles, the cardiovascular risk of HeFH varies in each individual. Their variety of phenotypic features suggests the need for better risk stratification to optimize their therapeutic management. The current review summarizes three potential approaches, including (1) definition of familial hypercholesterolemia (FH)-related risk scores, (2) genetic analysis, and (3) biomarkers. The International Atherosclerosis Society has recently proposed a definition of severe FH to identify very high-risk HeFH subjects according to their clinical characteristics. Furthermore, published studies have shown the association of FH-related genetic phenotypes with ASCVD, which indicates the genetic analysis’s potential to evaluate individual cardiovascular risks. Biomarkers reflecting disease activity have been considered to predict the formation of atherosclerosis and the occurrence of ASCVD in HeFH subjects. Incorporating these risk stratifications will be expected to allocate adequate intensity of lipid-lowering therapies in HeFH subjects, which ultimately improves cardiovascular outcomes.
The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition.
The proprotein convertase subtilisin kexin type-9 inhibitor ...evolocumab produced coronary atheroma regression in statin-treated patients.
Patients with a non–ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated.
Among treated patients, (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol LDL-C, 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (−57.5o vs. −31.4o; P = 0.04) and macrophage index (−3.17 vs −1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (−2.29% ± 0.47% vs −0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium.
The combination of statin and evolocumab after a non–ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697)
Display omitted
The fixation of titanium implants in bone tissue is affected by the presence of a passive titanium oxide (TiO2) layer. Specifically, oxidation products in the amorphous TiO2 matrix enhance the ...mechanical properties of mineralized tissues. In addition, in vitro mineralization mediated by primary osteoblasts on amorphous TiO2 generates stiff tissues in a process that resembles pathological mechanisms connected with tumors and proceeds through hydrogen peroxide-inducible clone-5 (Hic-5) expression. However, the relationship between surface-based peroxidation and stiff mineralized tissue formation remains unclear. In this study, titanium samples were processed using wire electrical discharge machining to generate oxidation products in amorphous TiO2. The gene expression profiles of primary osteoblasts cultured on these specimens were characterized. Increased expression of Hic-5 was correlated with the presence of peroxidation products. The crystallization of amorphous TiO2 in these samples reduced the expression of both Hic-5 and lysyl oxidase, an enzyme that promotes matrix cross-linking.
The fastening mechanics of prosthetic screws under various conditions is crucial to the maintenance of dental implants. This study comprehensively explores the prosthetic screw rupture in titanium ...(Ti) and zirconia (ZrO2) superstructures under wet and dry conditions. Superstructures were fabricated using digital technology and subjected to tightening torque trials. Experimental results suggested that the implications of the conventionally recommended torque of 15 N•cm differ significantly between dry and wet environments. Both Ti and ZrO2 exhibited preloads of >30 N•cm under dry conditions; however, differences emerged under wet conditions. In addition, screw rupture posed a prominent clinical challenge —particularly during long-term cyclic loading. Notably, the ZrO2 superstructures exhibited a greater resistance to breaking torque than that of Ti. This study underscores the importance of reevaluating torque recommendations with consideration to the distinct characteristics of Ti and ZrO2 in diverse environments.
This study aimed to non-destructively analyze the progression of subsurface enamel caries using swept-source optical coherence tomography (SS-OCT), a recently developed imaging analysis modality. ...Artificial enamel caries at various stages of demineralization were created in bovine tooth enamel using a modified lactic acid gel system. Untreated enamel served as a control. OCT images from cross-sections of enamel were collected. Mineral density, distribution, and histological changes were analyzed using an electron probe microanalyzer, scanning electron microscopy, and contact microradiography. The Raman spectrum and X-ray structural analysis of the enamel surfaces were determined. SS-OCT detected significant differences in mineral loss among the samples. A high-brightness image was confirmed, along with changes in the respective brightness graphs proportionate to the degree of demineralization. SS-OCT can potentially be used to evaluate the progression of incipient enamel carious lesions.
Numerous experimental studies have examined how much orthodontic force is needed to move teeth more smoothly; however, no reports have examined this clinically in individual, living subjects. We ...aimed to develop a method for quantifying the force exerted on individual teeth by an orthodontic wire to measure how loads placed on crowded teeth change dynamically over time. Accordingly, we fabricated a series of dental casts of patients undergoing orthodontic treatment (using optical impressions and a three-dimensional printer), fitted these models with nickel-titanium wire, and subjected them to bending load tests. During leveling, nickel-titanium wire is generally considered to exert a weak force due to its low elastic modulus, with a weak orthodontic force applied over a long period of time due to its superelasticity; however, we found that the actual energy exerted by nickel-titanium wire is also largely affected by other factors (e.g., amount of crowding).
PDF
