Editorial
Relationship between Atherogenic Dyslipidemia and Target Lesion Revascularization Post Everolimus-Eluting Stent Implantation
2023 Volume 30 Issue 12 Pages 1761-1762
Details
2023 Volume 30 Issue 12 Pages 1761-1762
See article vol. 30: 1778-1790
Hypercholesterolemia, an increase in the low-density lipoprotein cholesterol (LDL-C) level, is one of the most important causal risk factors for cardiovascular (CV) diseases. At present, lowering the LDL-C level is considered to be the most effective strategy for preventing CV events; thus, we are using statins, ezetimibe, and PCSK9 inhibitors to achieve further reduction in this level. In the recent guidelines of the Japan Atherosclerosis Society (JAS), an optimal LDL-C goal for secondary prevention is ＜70 mg/dL in patients with acute coronary syndrome, familial hypercholesterolemia, diabetes, and both coronary artery disease (CAD) and atherothrombotic strokes1). However, not all patients, with ＜70 mg/dL LDL-C level, treated with statins are preventable to CV events.
Fasting and non-fasting triglyceride (TG) levels are associated with CV events among the Japanese1). Recently, non-fasting measurement of TG levels was recommended for CV risk assessment by the European Atherosclerosis Society and JAS1). High TG levels are affected by the accumulation of TG-rich lipoproteins and their remnant lipoproteins; remnant lipoproteins’ accumulation enhanced atherogenicity in patients with hypertriglyceridemia2).
In this issue of the journal, Kimura et al. retrospectively evaluate the relationship between atherogenic dyslipidemia (AD) and target lesion revascularization (TLR) in 3,014 lesions from 2,022 consecutive patients who underwent everolimus-eluting stent (EES) implantation3). The authors defined AD as a combination of non-fasting TG ≥ 175 mg/dL and high-density lipoprotein cholesterol (HDL-C) ＜40 mg/dL based on the new JAS guidelines. They found important evidence; AD was associated with a significantly increased incidence of clinically driven TLR after EES implantation (HR 2.31, 95% CI 1.43–3.73, P=0.0006). Subgroup analysis showed that AD increased the risk of TLR with small stent implantations (≤ 2.75 mm). Multivariable Cox regression analysis showed that AD was an independent predictor of TLR in the small EES stratum (adjusted HR 3.00, 95% CI 1.53–5.93, P=0.004), whereas TLR incidence was similar in the non-small EES stratum, irrespective of the presence or absence of AD.
In a clinical study using intravascular ultrasound, a higher TG level was associated with a greater increase in plaque volume in patients with CAD4). Additionally, high TG levels were associated with a higher prevalence of vulnerable plaques, evaluated by optical coherence tomography5); Thus, TG levels affect not only plaque progression/regression but also vulnerability. Previous imaging-based studies demonstrated that neointimal hyperplasia (NIH) was the main cause of in-stent restenosis (ISR) in the early phase (within 1 year), whereas neoatherosclerosis (NA) was dominant in the late phase (beyond 1 year)6). The authors speculated that NIH and NA were involved in TLR mechanisms in small-stent-use among patients with AD, because the difference in the TLR Kaplan–Meier curve between AD and non-AD patients was observed in the early period (＜1 year), and the curve diverted gradually in the late period (＞1 year).
High TG or low HDL-C levels alone is an independent predictor for CV events. However, isolated hypertriglyceridemia and low HDL-C did not affect TLR prevalence in the present study. A previous meta-analysis showed that there was no significant correlation between the decrease in TG level and the prevalence of CV events7). In the ACCORD Lipid study, the combination of fenofibrate and simvastatin did not reduce the rate of CV events, whereas fenofibrate improved primary and secondary CV outcomes in a specific subclass of high TG and low HDL-C levels8). This combination of high TG and low HDL-C is usually observed when remnant lipoproteins are accumulated2). Therefore, to prevent CV events in patients with hypertriglyceridemia, considering effective interventions for improving atherogenic lipoprotein profile, such as high levels of small dense LDL, oxidized LDL, and remnant-like particle cholesterol, is important.
In a recent PROMINENT trial, the incidence of CV events was not lower among those who received pemafibrate, a novel selective peroxisome proliferator-activated receptor α agonist, than those who received placebo among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels9). In contrast, it was reported that pemafibrate suppresses coronary stent-induced arterial inflammation and NIH after bare metal stents implantation10). Although further experimental studies are needed to determine the efficacy of pemafibrate on NIH suppression in drug-eluting stents (DES), it is noteworthy that ISR remains a substantial clinical problem even in the DES era. Therefore, the results of this study provide an effective risk stratification in patients with EES implantation.
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