In this present study, the main findings were as follows: (1) The patients achieved a LDL-C goal had a higher QFR and a lower DS% or AS% at one-year follow-up, indicating a better improvement in coronary physiology. (2) A positive consistent tendency was presented in coronary physiology assessment (higher QFR) and clinical outcome (lower incidence of MACCEs), which increases the support to LDL-C goal achievement recommendation from a perspective of multidisciplinary assessments.
In view of coronary physiology, we found that patients with lower level of LDL-C tend to have a higher QFR value at the time of follow-up. Yellow trial study has suggested that improvement in FFR is associated with lower level of LDL-C conducted by LLT [10]. The mechanism of FFR changes in patients treated with LLT is speculated upon plaque burden and endothelial function [15]. Ito T, et al. found that the plaque burden of a stented segment affects the FFR value rather than the luminal area after optimal drug-eluting stent implantation [16]. Another study by Kolozsvári R, et al. suggested that both luminal narrowing and plaque burden may affect the FFR derived from Computed Tomography (CT) scanning [17]. In addition, previous studies have shown that endothelial function may also affect the FFR value, albeit the mechanism is not completely understood [18, 19]. QFR has a similar computational formula to FFR [20, 21]. Thus, we hold the opinion that plaque burden and endothelial function are the main factors to influence QFR value in addition to narrowing lumen resulted from significant stenosis. Videlicet, a more satisfactory level of QFR value may reflect a better improvement in plaque burden or endothelial function in patients without significant stenosis.
Patients achieved LDL-C goal seemed to have a better result in coronary physiology assessment. Previous study concerning non-culprit plaque suggested that DS% can increase by 2.2% even with routine LLT [22]. Our study showed a 0.6% increase in patients achieved a LDL-C goal, and a 3.3% increase in those not achieved goal, respectively. It seems that LDL-C goal achievement may alleviate the deterioration of non-culprit. In addition, LLL is an index to evaluate the absolute degree of restenosis and the status of the intimal hyperplasia in coronary artery [23]. No significant difference in LLL was found between two groups (p = 0.172), albeit the QFR value of patients achieved goal was higher (p = 0.005). Furthermore, lower incidence of physiological restenosis was recorded in goal-achievement group compared to non-achievement group. These QCA analysis results indicate that patients achieved a LDL-C goal may have a better improvement in coronary physiology. From the perspective of vascular physiology, the potential benefit of LDL-C goal achievement is verified.
The incidence of MACCEs was significantly lower in patients achieved a LDL-C goal. Previous studies have demonstrated clinical benefit from LLT, namely, the greater the absolute LDL-C reduction, the greater the cardiovascular risk reduction [24, 25]. Our study showed a consistent result concerning incidence of MACCE with previous researches. Nevertheless, no statistically significant differences were found in stroke, target or non-target vessel revascularization in our study. The small numbers of patients in these subgroups may account for this elusive statistical result. Although goal-achievement group not showed a statistical difference in revascularization, this group of patients was still reported with a lower incidence of revascularization in numerical result. Therefore, our finding suggests that LDL-C management is of significance in cardiovascular events prevention. In addition, a positive accordant tendency was presented in coronary physiology and clinical outcome, which provides new evidence to support the LDL-C goal achievement recommendation.
For patients at very high cardiovascular risk, whether in secondary prevention or in primary prevention, a more aggressive LDL-C reduction goal are recommended according to The ESC/ EAS 2019 guidelines [3]. However, the proportion of patients achieved a LDL-C goal is still unsatisfied. In our study, only 31.0% of enrolled patients achieved a LDL-C goal even though the statin was prescribed to all participants. It may be due to the underdose of statin or insufficient concomitant use of other hypolipidemic drugs. Therefore, there is considerable potential to optimize lipid-lowering therapy further through statin intensification and appropriate use of novel LLT.
Our study still has some limitations. First, this is a observational study at a single center with a short time follow-up, the findings need to be verified by further prospective multi-center cohort studies. Second, some other treatment of risk factors may affect the incidence of MACCE, while not be discussed in our study. Third, not all images are suitable for QFR analysis, so it may affect the selection of some patients during QFR measurement.