Characterization of residual lipid-rich plaques despite achieving LDL-C <1.8mmol/l with a statin in patients with coronary artery disease: insights from the REASSURE-NIRS registry

Introduction Recent studies have demonstrated favourable modification of lipidic plaque materials under achieving LDL-C &lt;1.8mmol/l with a statin, which potentially accounts for its clinical benefit. However, coronary events still occur even under optimal LDL-C management. This may suggest the presence of residual lipid-rich coronary plaque despite on-treatment LDL-C &lt;1.8mmol/l. Given that near-infrared spectroscopy (NIRS) enables quantitative evaluation of lipidic plaque in vivo, we employed this imaging modality to investigate characteristics and drivers of residual lipid-rich plaques in statin-treated patients with coronary artery disease (CAD) who achieved LDL-C &lt;1.8mmol/l. Purpose To clarify the frequency, clinical demographics and factors associated with residual lipid-rich plaques under LDL-C &lt;1.8mmol/l. Methods The REASSURE-NIRS registry is an on-going multi-center registry to enroll CAD subjects receiving NIRS/intravascular ultrasound-guided PCI. The current analysis included 133 statin-treated stable CAD patients with on-treatment LDL-C &lt;1.8mmol/l from August 2015 to December 2020. The maximum 4-mm lipid core burden index (maxLCBI4mm) at culprit lesions was measured by NIRS imaging prior to PCI. Clinical characteristics were compared in patients with and without maxLCBI4mm ≥400 at culprit lesions. Results In the current study, 45% (=58/128) of study subjects exhibited maxLCBI4mm ≥400 at culprit lesions under on-treatment LDL-C &lt;1.8 mmol/l. They were more likely to be female, whereas there were no differences in age and the frequency of risk factors. Most of study subjects received moderate to high-intensity statin (p=0.79), and over one-fourth of them were treated with ezetimibe (p=0.56). Under these lipid-lowering therapies, LDL-C level was significantly higher in patients with maxLCBI4mm ≥400 (Table). Additionally, a lower frequency of LDL-C &lt;1.4mmol/l was observed in those exhibiting maxLCBI4mm ≥400 (31.0 vs. 45.7%), but this comparison failed to meet statistical significance (p=0.09). Despite LDL-C control with a statin, deterioration of coronary flow after PCI with stent implantation more frequently occurred in patients with maxLCBI4mm ≥400 (Table). Multivariate analysis demonstrated that an independent factor associated with maxLCBI4mm ≥400 was LDL-C level (OR=1.05; 95% CI=1.00–1.10, p=0.03), but not other lipid and clinical parameters. Conclusion Almost half of CAD subjects who achieved LDL-C level &lt;1.8mmol/l still exhibited the accumulation of lipidic plaque materials within vessel wall. Given that LDL-C level was associated with this residual lipid-rich plaque features, our findings support current ESC-guideline recommended LDL-C goal (&lt;1.4mmol/l) to optimize the secondary prevention in stable CAD patients. Funding Acknowledgement Type of funding sources: None.

Assessment of the Defatting Efficacy of Mechanical and Chemical Treatment for Allograft Cancellous Bone and Its Effects on Biomechanics Properties of Bone

Background To assess the defatting efficacy of high pressure washing and gradient alcohol and biomechanical properties of defatted bone. Methods Fresh cancellous bone was obtained from the femoral condyle and divided into 6 groups according to different defatting treatments, which were high pressure washing for 10 seconds (10S group), 20 seconds (20S group), 30 seconds (30S group), gradient alcohol immersion (Alcohol group), acetone immersion (Acetone group), and non-defatted (Fresh group). The appearance of 6 groups was observed, comparing the appearance difference between defatted bone and fresh bone. The residual lipid content and infrared spectrum were used to compare the efficacy of defatting, the DNA content was used to compare the cell content after defatting, and the maximum stress and elastic modulus were used to compare the effects of defatting treatment on biomechanical properties. Results The fresh bone was yellow and the pores contained a lot of fat. The defatted bone was white and the porous network was clear. No difference in residual lipid content among the three groups under high pressure washing (1.45 ± 0.16%, 1.40 ± 0.13%, 1.46 ± 0.11%, respectively) ( p = 0.828). No difference in residual lipid content among the 10S, alcohol, and acetone groups (1.45 ± 0.16%, 1.28 ± 0.07%, 1.13 ± 0.22%, respectively) ( p = 0.125). Infrared spectra showed that the fat content of the five defatting groups was significantly lower than that of the fresh group. No difference in residual lipid content among the three groups under high pressure washing (4.53 ± 0.23ug/ml, 4.61±0.18ug/ml, 4.66 ± 0.25ug/ml, respectively) ( p = 0.645). No difference in residual lipid content among the 10S, alcohol, and acetone groups (4.53 ± 0.23ug/ml, 4.29 ± 0.24ug/ml, 4.27±0.29ug/ml, respectively) ( p = 0.247). The maximum stress of the bone decreased significantly with the increase of the washing time (9.95 ± 0.31Mpa, 9.07 ± 0.45Mpa, 8.17 ± 0.35Mpa, respectively) ( p = 0.003). The elastic modulus of the bone decreased significantly with the increase of the washing time (116.40 ± 3.54Mpa, 106.10 ± 5.29Mpa, 95.63 ± 4.08Mpa, respectively) ( p = 0.003). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group and the acetone group (10.09 ± 0.67Mpa, 9.95 ± 0.31Mpa, 10.11 ± 0.07Mpa, 10.09 ± 0.39Mpa) ( p = 0.963). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group and the acetone group (119.93 ± 4.94Mpa, 116.40 ± 3.54Mpa, 118.27 ± 0.85Mpa, 118.10 ± 4.52Mpa) ( p = 0.737). Conclusion The results of this experiment indicate that the defatting efficiency was satisfactory at a time of 10 seconds under high pressure washing. High pressure washing and gradient alcohol were similar to conventional acetone solvent extraction defatting.

ACUTE CORONARY SYNDROME: A SEA CHANGE IN OUR UNDERSTANDING OF PATHOGENESIS AND WAY OF TREATMENT? (PART II)

The second part of review highlights the role of residual lipid and thrombotic risks in coronary heart disease patients and possible ways of its correction. The results of randomized clinical trials dedicated to the efficacy of new class of hypolipidemic drug (PCSK‑9 inhibitors) in acute coronary syndrome setting are discussed. Recently published new guidelines of European Society of Cardiology on acute coronary syndrome management are also highlighted.

A residualis kockázat útvesztői: a maradék lipid és gyulladásos kockázat csökkentése az atherosclerosis prevenciójában

Since cardiovascular diseases are the main cause of mortality worldwide, the reduction of their risk is a crucial point of present-day medicine. It has been proven unequivocally that the administration of various treatments has a favorable effect on the frequency of cardiovascular events and on the atherosclerosis leading to them. Although systematic and guideline-driven administration of these drugs has led to a decrease in the incidence and mortality of vascular events, the leading position of this group of diseases in mortality and morbidity has not changed. That is why medicine, besides keeping up actual guidelines optimally, is always searching for new modalities to further decrease residual risk. This residual risk can be diverse. The present paper summarizes the possibilities of reducing residual lipid and residual inflammatory risk after treatment according to the guidelines. It has been proven that lowering LDL-cholesterol below 1.8 mmol/l has a further advantage on the occurrence of vascular events. Treating the elevated lipoprotein(a), triglyceride and low HDL-cholesterol levels should decrease the residual lipid risk. Statins and statin-ezetimibe combination, besides lipid modulation, have an anti-inflammatory effect proved by C-reactive protein level reduction. Canakinumab has solely inflammation reducing effect through the inhibition of interleukin-1β. It was administered subcutaneously once in 3 months in a large-scale clinical study and it has shown a 15% reduction in non-fatal myocardial infarction, non-fatal stroke and cardiovascular death, which opens new horizons in the anti-inflammatory treatment of atherosclerosis. Orv Hetil. 2018; 159(4): 124–130.

Kinetics and utilization of lipid sources during acute exercise and acipimox

Overweight is associated with abnormalities of lipid metabolism, many of which are reversed by exercise. We investigated the impact of experimental antilipolysis and acute exercise on lipid kinetics and oxidation from VLDL-TG, plasma FFA, and “residual lipids” in overweight men ( n = 8) using VLDL-TG and palmitate tracers in combination with muscle biopsies in a randomized, placebo-controlled design. Participants received placebo or acipimox on each study day (4 h of rest, 90 min of exercise at 50% V̇o2 max). Exercise suppressed VLDL-TG secretion significantly during placebo but not acipimox (placebo-rest: 64.2 ± 9.4; placebo-exercise: 48.3 ± 8.0; acipimox-rest: 55.2 ± 13.4; acipimox-exercise: 52.0 ± 10.9). Resting oxidation of VLDL-TG FA and FFA was significantly reduced during acipimox compared with placebo, whereas “residual lipid oxidation” increased significantly [VLDL-TG oxidation (placebo: 18 ± 3 kcal/h; acipimox: 11 ± 2 kcal/h), FFA oxidation (placebo: 14 ± 2 kcal/h; acipimox: 4 ± 0.5 kcal/h), and residual lipid oxidation (placebo: 3 ± 5 kcal/h; acipimox: 14 ± 5 kcal/h)]. Additionally, during exercise on both placebo and acipimox, oxidation of VLDL-TG and FFA increased, but the relative contribution to total lipid oxidation diminished, except for FFA, which remained unchanged during acipimox. Residual lipid oxidation increased significantly during exercise in both absolute and relative terms. Changes in selected cellular enzymes and proteins provided no explanations for kinetic changes. In conclusion, suppressed FFA availability blunts the effect of exercise on VLDL-TG secretion and modifies the contribution of lipid sources for oxidation.