Impact of body mass index on repeat coronary revascularization rates in patients with LDL-C below 55 mg/dL and LDL-C below 70 mg/dL: a 42-month cohort study in Korea

Introduction

Background

The “obesity paradox” refers to the observations that obese patients with a particular disease such as cardiovascular disease and cancer may have better outcomes than their normal weight or underweight patients (1). This observation has been also elucidated in patients who underwent percutaneous coronary intervention (PCI) (2-5).

Rationale and knowledge gap

However, most previous studies of the obesity paradox have focused on its impact on survival outcomes (1-4), whereas other studies focusing on repeat revascularization have revealed a linear relationship between body mass index (BMI) and repeat coronary revascularization rates (6-9). Influenced by 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidemia guidelines, the recent Korean dyslipidemia guidelines changed the target low-density lipoprotein cholesterol (LDL-C) levels of coronary artery disease (CAD) patients from less than 70 mg/dL to less than 55 mg/dL (10,11). However, there are not enough studies on Korean CAD patients to support this change. In addition, the relationship between obesity and repeat coronary revascularization rate has not been demonstrated in Korean CAD patients who meet old and new target LDL-C level of Korean dyslipidemia guidelines.

Objectives

Therefore, we conducted this study to find out the effect of BMI on repeat coronary revascularization rate in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL after PCI. We present this article in accordance with the STROBE reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-27/rc).

Methods

Study population and data collection

We included 1,361 patients from the PCI registry at the Daegu Catholic Medical Center (Daegu, Korea). All patients underwent first PCI using drug-eluting stents (DES) between October 2005 and February 2018 and started statin treatment. Among 1,361 patients, 465 patients who were followed up with an LDL-C level of less than 70 mg/dL one year after PCI were investigated. Of 465 patients, 18 patients who had end-stage renal disease (ESRD) and 18 patients whose BMI was below 18.5 kg/m² were excluded. Finally, we included 429 patients. The flow of the study is shown in Figure 1. Major adverse cardiovascular events (MACEs) evaluation began from the time of the LDL-C follow-up. We defined MACEs as cardiac death, non-fatal myocardial infarction (MI), repeat coronary revascularization, and ischemic stroke. We followed the MI definition as the third universal definition (12). The lipid profile of participant at the time of index PCI and at the time of follow-up was investigated. The lipid profiles included measurements of lipoprotein (a) [Lp(a)], triglyceride (TG), total cholesterol (TC), LDL-C, high density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1). We also evaluated clinical and angiographical data. Prescribed statins were investigated at baseline and follow-up. Statins were classified as high intensity statin, moderate intensity statin, low intensity statin based on the American College of Cardiology (ACC) guideline (13). Other essential medications including antiplatelet, β-blockers, calcium channel blockers, and renin-angiotensin system (RAS) blockers were also prescribed and associated data were collected. We classified coronary lesions into three groups (A, B, and C), with group B (intermediate risk) further divided into class B1 and B2 according to the presence of 1 or 2 adverse characteristics (14). Patients were divided into normal weight group, pre-obesity group and obesity group according to their BMI. Regarding the definition and classification of obesity, we followed the 2022 Korean Obesity Guidelines for the definition of obesity (underweight: BMI <18.5 kg/m², normal weight: 18.5 kg/m² ≤ BMI <23 kg/m², pre-obesity: 23 kg/m² ≤ BMI <25 kg/m², obesity: 25 kg/m² ≤ BMI) (15). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board at Daegu Catholic Medical Center (No. CR-22-180) and the requirement for patient informed consent was waived due to the study’s retrospective nature.

Figure 1 Progress of study. DCMC, Daegu Catholic Medical Center; PCI, percutaneous coronary intervention; LDL-C, low-density lipoprotein cholesterol; ESRD, end-stage renal disease; BMI, body mass index.

PCI procedure and statin usage

PCI was performed by conventional methods and the type of DES was selected by attending physician. Dual oral antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel, 180 mg ticagrelor, or 10 mg prasugrel) was maintained to patients for at least 12 months after PCI. Every patient was discharged with a statin, and the type of statin was selected by attending physician.

Statistical analysis

Quantitative data were presented as the number (%), mean ± standard deviation. We compared categorical data using the chi-square test or Fisher’s exact test. We compared continuous variables using a student’s t-test when normally distributed and Kruskal-Wallis H test when non-normally distributed. Kaplan-Meier survival curves were used for the analysis of repeat revascularization-free survival and compared using the log-rank test between different groups. We performed univariate and multivariate Cox proportional hazards regression to determine the independent predictors for repeat revascularization. Variables were fully included in the multivariate analysis and the stepwise regression method was used. To compare the predicting performance of BMI for repeat revascularization, receiver operating characteristic curves were presented in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL, and area under the curve (AUC) was measured. The optimal cut-off value was determined by Youden index. P (two-sided) <0.05 was considered statistically significant. Statistical analyses were performed using SPSS version 25 (IBM, Armonk, NY, USA).

Results

Comparison of clinical characteristics between LDL-C <55 mg/dL group and LDL-C <70 mg/dL group

There were 157 patients in the LDL-C <55 mg/dL group and 429 patients in the LDL-C <70 mg/dL group (Table 1). In LDL-C <70 mg/dL group, the mean age was 63.00±10.51 years, 73.4% were men. The mean BMI was 23.92±2.87 kg/m². There was no significant difference in clinical characteristics comparing the two groups. Procedural characteristics including multi-vessel disease (MVD), usage of 1^st generation DES, and type b2/c lesions also showed no significant difference. At the time of lipid profile follow-up, the mean LDL-C level was 44.64±7.68 mg/dL in LDL-C <55 mg/dL group and 56.11±10.54 mg/dL in LDL-C <70 mg/dL group (P<0.001). There were also significant differences in TC, TG, Apo B and LDL-C % reduction between LDL-C <55 mg/dL group and LDL-C <70 mg/dL group.

Comparison of repeat revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL

During a median follow-up period of 42.0 months, there was no significant difference in repeat revascularization-free survival between LDL-C <55 mg/dL group and LDL-C <70 mg/dL group [79.6% vs. 76.2%, hazard ratio (HR) 1.221, 95% confidence interval (CI): 0.8211–1.814, P=0.32, Figure 2A]. In normal weight patients, LDL-C <55 mg/dL group showed higher repeat coronary revascularization-free survival than LDL-C <70 mg/dL group (89.3% vs. 77.1%, HR: 2.225, 95% CI: 1.134–4.364, P=0.05, Figure 2B). In the pre-obesity group, there were no significant differences of repeat coronary revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL (77.5% vs. 80.9%, HR: 0.8635, 95% CI: 0.4140–1.801, P=0.67, Figure 2C). In the obesity group, there were no significant differences of repeat coronary revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL (71.1% vs. 70.8%, HR: 1.060, 95% CI: 0.5901–1.904, P=0.83, Figure 2D).

Figure 2 Comparison of repeat revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL. (A) Comparison of repeat revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL. (B) Comparison of repeat revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL in normal weight patients. (C) Comparison of repeat revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL in pre-obesity patients. (D) Comparison of repeat revascularization-free survival between LDL-C <55 mg/dL and LDL-C <70 mg/dL in obesity patients. CI, confidence interval; LDL-C, low-density lipoprotein cholesterol.

Comparison of repeat revascularization-free survival between the normal body weight group and the pre-obesity and obesity group in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL

There was no significant difference in repeat revascularization-free survival between the normal weight group and the pre-obesity and obesity group in patients with LDL-C <70 mg/dL (77.1% vs. 75.7%, HR: 1.157, 95% CI: 0.7835–1.709, P=0.67, Figure 3A). However, the normal weight group showed significantly higher repeat revascularization-free survival compared to the pre-obesity and obesity group in patients with LDL-C <55 mg/dL (89.3% vs. 74.3%, HR: 2.405, 95% CI: 1.167–4.957, P=0.03, Figure 3B).

Figure 3 Comparison of repeat revascularization-free survival between the normal body weight group and the pre-obesity and obesity group. (A) Comparison of repeat revascularization-free survival between the normal body weight group and the pre-obesity and obesity group in patients with LDL-C <70 mg/dL. (B) Comparison of repeat revascularization-free survival between the normal body weight group and the pre-obesity and obesity group in patients with LDL-C <55 mg/dL. LDL-C, low-density lipoprotein cholesterol; CI, confidence interval.

Comparison of characteristics between normal body weight vs. pre-obesity and obesity in patients with LDL-C <55 mg/dL and in patients with LDL-C <70 mg/dL

We compared the clinical characteristics and lipid profiles between the normal body weight group and the pre-obesity and obesity group in patients with LDL-C <70 mg/dL and in patients with LDL-C <55 mg/dL (Table 2). In patients with LDL-C <70 mg/dL, the pre-obesity and obesity groups were significantly younger than normal body weight group. The mean BMI was 21.27±1.21 kg/m² in the normal body weight group, 25.60±2.30 kg/m² in the pre-obesity and obesity group (P<0.001). At lipid profile follow-up, TG, Apo B were significantly lower in the normal body weight group (TG: P<0.001, Apo B: P<0.001). HDL-C was significantly higher in the normal body weight group (P=0.001). In patients with LDL-C <55 mg/dL, the mean BMI was 20.95±1.28 kg/m² in the normal body weight group, 25.33±1.79 kg/m² in the pre-obesity and obesity group (P<0.001). At lipid profile follow-up, Apo B was significantly lower in normal body weight patients (P=0.01).

Comparison of MACEs rate among the normal body weight group, the pre-obesity group, and the obesity group in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL

In patients with LDL-C less than 70 mg/dL, there was no linear relationship between BMI and MACE rate and between BMI and repeat revascularization rate (Figure 4A). However, in patients with LDL-C less than 55 mg/dL, the MACE rate and repeat revascularization rate tended to increase with increasing BMI (Figure 4B). The repeat revascularization rate in normal weight patients was 22.9% when LDL-C was less than 70 mg/dL, but it decreased to 10.7% when LDL-C was less than 55 mg/dL. On the other hand, there was no similar decrease of repeat revascularization rate in pre-obesity and obesity patients.

Figure 4 Comparison of MACEs rate among the normal body weight group, the pre-obesity group, and the obesity group. (A) Comparison of MACEs rate among the normal body weight group, the pre-obesity group, and the obesity group in patients with LDL-C <70 mg/dL. (B) Comparison of MACEs rate among the normal body weight group, the pre-obesity group, and the obesity group in patients with LDL-C <55 mg/dL. MACE, major adverse cardiovascular event; MI, myocardial infarction; LDL-C, low-density lipoprotein cholesterol.

Predicting performance of BMI for repeat revascularization in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL

BMI showed better predictability for repeat revascularization in patients with LDL-C <55 mg/dL (AUC: 0.622, 95% CI: 0.531–0.712, P=0.025, Figure 5A) than in patients with LDL-C <70 mg/dL (AUC: 0.525, 95% CI: 0.460–0.589, P=0.454, Figure 5B). The cutoff BMI for repeat revascularization in patients with LDL-C <55 mg/dL was 22.0 kg/m².

Figure 5 ROC curves for repeat revascularization. (A) ROC curve for repeat revascularization in patients with LDL-C <55 mg/dL, (B) ROC curve for repeat revascularization in patients with LDL-C <70 mg/dL. LDL-C, low-density lipoprotein cholesterol; ROC, receiver operating characteristic; AUC, area under the ROC curve; BMI, body mass index; CI, confidence interval.

Independent predictors for MACE and repeat revascularization

We analyzed independent predictors for repeat revascularization by using univariate and multivariate Cox proportional hazards regression (Table 3). Normal body weight and LDL-C <55 mg/dL (HR: 0.421, 95% CI: 0.193–0.916, P=0.02) was the only independent predictor for repeat revascularization.

Discussion

Key findings

The primary findings of our study are as follows: (I) In Korean patients, there was no significant difference in repeat coronary revascularization-free survival between a group with LDL-C <55 mg/dL and a group with LDL-C <70 mg. (II) In patients with LDL-C <55 mg/dL, there was significantly higher repeat coronary revascularization-free survival in the normal weight group compared to the pre-obesity and obesity group. While, there was no significant difference of repeat coronary revascularization-free survival between the normal weight group compared to the pre-obesity and obesity group in patients with LDL-C <70 mg/dL. (III) In patients with LDL-C <55 mg/dL, the MACE rate and repeat revascularization rate showed linear relationship with BMI. (IV) Normal body weight and LDL-C <55 mg/dL was the only independent predictor for repeat revascularization in patients with LDL-C <70 mg/dL.

Comparison with similar researches

2019 ESC/EAS dyslipidemia guideline recommended LDL-C goal of <55 mg/dL and LDL-C reduction of ≥50% from baseline in patients with atherosclerotic cardiovascular disease (ASCVD) (9). The LDL-C target for patients with ASCVD in the ESC/EAS dyslipidemia guideline is based primarily on recent large-scale trials of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which mainly conducted in Western populations (16,17). Influenced by 2019 ESC/EAS dyslipidemia guidelines, the recent Korean dyslipidemia guidelines changed the target LDL-C level of CAD patients from less than 70 mg/dL to less than 55 mg/dL (11). There were prior studies about optimal LDL-C levels of CAD patients in Korea and Japan. However, they did not demonstrate the benefit of lowering target LDL-C level from 70 to 55 mg/dL. Ahn et al. compared MACE incidence between LDL-C <55 mg/dL and LDL-C <70 mg/dL in Korean acute myocardial infarction (AMI) patients. There was no significant difference of MACE incidence between the two groups (18). Sakuma et al. demonstrated that cardiovascular risk is maintained even when LDL-C is lowered to less than 70 mg/dL in Japanese CAD patients (19). As in the previous studies, there was no significant difference in clinical outcomes between LDL-C less than 55 mg/dL and LDL-C less than 70 mg/dL in present study. However, we found that in patients with normal body weight, LDL-C <55 mg/dL have higher repeat coronary revascularization-free survival compared to LDL-C <70 mg/dL. The results of the present study are consistent with previous studies which demonstrated that more LDL-C lowering with intensive lipid lowering therapy (LLT) is more effective in normal body weight patients than in obese patients. Nylén et al. showed that in type 2 diabetic male veterans, statin therapy removed the increased mortality associated with BMI <25 kg/m² (20). Khan et al. also demonstrated intensive LLT derived the highest cardiovascular risk reduction in patients with BMI <25 kg/m² compared with patients with BMI ≥30 kg/m². They concluded that normal weight patients may have a larger clinical benefit (cardiovascular mortality, all-cause mortality, MI, revascularization, MACE) from intensive LLT compared with obese patients. Khan et al. explained their research results with the following three mechanism (21). First, characteristics of the dyslipidemia of obese patients include elevated TC, TG, and very low-density lipoprotein cholesterol with lower HDL-C levels. Statins only slightly lower TG and do not completely correct the characteristic dyslipidemia seen in obesity, which poses a residual risk after statin treatment. Second, increased levels of inflammation in obese patients may pose a residual cardiovascular risk even after LLT. Third, obesity is associated with decreased expression of LDL receptors, which may modulate the efficacy of LLT.

The “obesity paradox” has been elucidated in patients who underwent PCI. Most previous studies on the obesity paradox have concentrated on its impact on survival (2-5). The main mechanism of the obesity paradox has been suggested to be the low incidence of post-procedural bleeding complications and the long-term, intensive use of medication in obese patients (22,23). The present study differs from previous obesity paradox studies in the following ways: First, we investigated the MACE rate that occurred 1 year after PCI excluding the MACE rate within 1 year of PCI. Second, we included patients whose LDL-C remained very low for a long time. Therefore, this study is unique in that it included patients who were discharged without complications after PCI and satisfied LDL-C levels of the Korean dyslipidemia guidelines for a long time. Third, Tan et al. demonstrated that long-term intensive drug use was the cause of the obesity paradox after PCI (23). Biswas also showed that obese patients tend to have increased use of guideline-based medical therapy, in particular β-blockers, renin-angiotensin-system blockers, and statins (5). However, there were no differences of medication use between the normal body weight group and pre-obesity, obesity group in our study (Table 2). Therefore, we believe that this study showed that obesity has an independent impact on prognosis after PCI by eliminating factors such as acute complications or medication use. Other studies that focused on repeat revascularization revealed a linear relationship BMI and repeat coronary revascularization rate (6-9). Nikolsky et al. suggested that the linear relationship between BMI and repeat coronary revascularization rate may be related to insulin resistance of obese patients (8). Insulin resistance is a well-known risk factor of in-stent restenosis. Previous studies have reported that insulin resistance causes the proliferation of vascular smooth muscle cells after stent implantation (24-26).

Explanations of findings, implications and actions needed

The results of the present study also showed the linear relationship between BMI and repeat coronary revascularization rate in patients with LDL-C <55 mg/dL. The repeat revascularization rate in normal weight patients was 22.9% when LDL-C was less than 70, but it decreased to 10.7% when LDL-C was less than 55. On the other hand, there was no similar decrease of repeat revascularization rate in pre-obesity and obesity patients. It seems that lowering the LDL-C level from less than 70 to less than 55 did not reduce the repeat coronary revascularization rate of obese patients due to insulin resistance. In the present study, normal body weight and LDL-C <55 mg/dL was the only independent predictor for repeat revascularization. Therefore, Korean PCI patients with normal body weight whose LDL-C level is less than 70 mg/dL, but more than 55 mg/dL, should be treated with more intensive LLT to lower LDL-C to less than 55 mg/dL. For obese patients who have succeeded in reducing LDL-C below 55 mg/dL after LLT, it seems that weight loss should be attempted to a normal body weight level. We excluded underweight patient in our study with following reasons. First, underweight has been reported as an important risk factor for cardiac death after MI (27-29). Second, underweight patients are more likely to have old age, a higher prevalence of most comorbidities and measures of frailty (27). We excluded underweight patients from this study because these clinical findings related to underweight could bias the results of the present study.

Strength and limitations

Our study had several limitations. First, because this study was retrospective, the blood test period and clinical follow-up period for each patient were different, and statin use was also inconsistent. However, since this study targeted patients whose LDL-C decreased to less than 70 mg/dL one year after PCI, the patient’s compliance was excellent and the clinical follow-up period was sufficiently long. Second, the recent Korean dyslipidemia guidelines also recommended reducing LDL-C by ≥50% from the baseline level. However, we did not include a ≥50% reduction in LDL-C as an inclusion criterion. In this respect, our study did not fully meet the Korean dyslipidemia guidelines. To date, the relationship between obesity and repeat coronary revascularization rate has not been demonstrated in Korean patients who meet old and new target LDL-C level of Korean dyslipidemia guidelines. Therefore, this study is significant as it is the first study to investigate the relationship between obesity and clinical outcomes in Korean patients who satisfied the new target LDL-C level of Korean dyslipidemia guidelines after PCI.

Conclusions

In Korean PCI patients with normal body weight whose LDL-C level is less than 70 mg/dL, but more than 55 mg/dL, should be treated with more intensive therapy to lower LDL-C to less than 55 mg/dL. For obese patients who have succeeded in reducing LDL-C below 55 mg/dL, it seems that weight loss should be attempted to a normal body weight level.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-27/rc

Data Sharing Statement: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-27/dss

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-27/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-27/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board at Daegu Catholic Medical Center (No. CR-22-180) and the requirement for patient informed consent was waived due to the study’s retrospective nature.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Dramé M, Godaert L. The Obesity Paradox and Mortality in Older Adults: A Systematic Review. Nutrients 2023;15:1780. [Crossref] [PubMed]
2. Qu Y, Yang J, Zhang F, et al. Relationship between body mass index and outcomes of coronary artery disease in Asian population: Insight from the FOCUS registry. Int J Cardiol 2020;300:262-7. [Crossref] [PubMed]
3. Gurevitz C, Assali A, Mohsan J, et al. The obesity paradox in patients with acute coronary syndromes over 2 decades - the ACSIS registry 2000-2018. Int J Cardiol 2023;380:48-55. [Crossref] [PubMed]
4. Won KB, Yoon HJ, Lee SG, et al. Comparison of long-term mortality according to obesity in patients with successful percutaneous chronic total occlusion interventions using drug-eluting stents. Catheter Cardiovasc Interv 2018;91:710-6. [Crossref] [PubMed]
5. Biswas S, Andrianopoulos N, Dinh D, et al. Association of Body Mass Index and Extreme Obesity With Long-Term Outcomes Following Percutaneous Coronary Intervention. J Am Heart Assoc 2019;8:e012860. [Crossref] [PubMed]
6. Sarno G, Räber L, Onuma Y, et al. Impact of body mass index on the five-year outcome of patients having percutaneous coronary interventions with drug-eluting stents. Am J Cardiol 2011;108:195-201. [Crossref] [PubMed]
7. Wang ZJ, Gao F, Cheng WJ, et al. Body Mass Index and Repeat Revascularization After Percutaneous Coronary Intervention: A Meta-analysis. Can J Cardiol 2015;31:800-8. [Crossref] [PubMed]
8. Nikolsky E, Kosinski E, Mishkel GJ, et al. Impact of obesity on revascularization and restenosis rates after bare-metal and drug-eluting stent implantation (from the TAXUS-IV trial). Am J Cardiol 2005;95:709-15. [Crossref] [PubMed]
9. Wang ZJ, Zhou YJ, Zhao YX, et al. Effect of obesity on repeat revascularization in patients undergoing percutaneous coronary intervention with drug-eluting stents. Obesity (Silver Spring) 2012;20:141-6. [Crossref] [PubMed]
10. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88. [Crossref] [PubMed]
11. Yang YS, Kim HL, Kim SH, et al. Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement. J Lipid Atheroscler 2023;12:12-22. [Crossref] [PubMed]
12. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012;126:2020-35. [Crossref] [PubMed]
13. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73:3168-209. [Crossref] [PubMed]
14. Konigstein M, Redfors B, Zhang Z, et al. Utility of the ACC/AHA Lesion Classification to Predict Outcomes After Contemporary DES Treatment: Individual Patient Data Pooled Analysis From 7 Randomized Trials. J Am Heart Assoc 2022;11:e025275. [Crossref] [PubMed]
15. Kim KK, Haam JH, Kim BT, et al. Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity. J Obes Metab Syndr 2023;32:1-24. [Crossref] [PubMed]
16. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018;379:2097-107. [Crossref] [PubMed]
17. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017;376:1713-22. [Crossref] [PubMed]
18. Ahn JH, Ahn Y, Jeong MH, et al. Optimal low-density lipoprotein cholesterol target level in Korean acute myocardial infarction patients (<70 mg/dL vs. <55 mg/dL): Based on Korea acute myocardial infarction registry-National Institute of Health. Int J Cardiol 2022;351:15-22. [Crossref] [PubMed]
19. Sakuma M, Iimuro S, Shinozaki T, et al. Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events. BMC Med 2022;20:441. [Crossref] [PubMed]
20. Nylén ES, Faselis C, Kheirbek R, et al. Statins modulate the mortality risk associated with obesity and cardiorespiratory fitness in diabetics. J Clin Endocrinol Metab 2013;98:3394-401. [Crossref] [PubMed]
21. Khan SU, Khan MU, Riaz H, et al. Meta-analysis of the Relation of Body Mass Index to Cardiovascular Outcomes in Patients Receiving Intensive Low-Density Lipoprotein Cholesterol Lowering Therapy. Am J Cardiol 2020;125:727-34. [Crossref] [PubMed]
22. Kim DW, Her SH, Park HW, et al. Association between body mass index and 1-year outcome after acute myocardial infarction. PLoS One 2019;14:e0217525. [Crossref] [PubMed]
23. Tan XF, Shi JX, Chen AM. Prolonged and intensive medication use are associated with the obesity paradox after percutaneous coronary intervention: a systematic review and meta-analysis of 12 studies. BMC Cardiovasc Disord 2016;16:125. [Crossref] [PubMed]
24. Zhao LP, Xu WT, Wang L, et al. Influence of insulin resistance on in-stent restenosis in patients undergoing coronary drug-eluting stent implantation after long-term angiographic follow-up. Coron Artery Dis 2015;26:5-10. [Crossref] [PubMed]
25. Takagi T, Yoshida K, Akasaka T, et al. Hyperinsulinemia during oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients: a serial intravascular ultrasound study. J Am Coll Cardiol 2000;36:731-8. [Crossref] [PubMed]
26. Piatti P, Di Mario C, Monti LD, et al. Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting. Circulation 2003;108:2074-81. [Crossref] [PubMed]
27. Bucholz EM, Krumholz HA, Krumholz HM. Underweight, Markers of Cachexia, and Mortality in Acute Myocardial Infarction: A Prospective Cohort Study of Elderly Medicare Beneficiaries. PLoS Med 2016;13:e1001998. [Crossref] [PubMed]
28. Su W, Wang M, Zhu J, et al. Underweight Predicts Greater Risk of Cardiac Mortality Post Acute Myocardial Infarction. Int Heart J 2020;61:658-64. [Crossref] [PubMed]
29. Bucholz EM, Rathore SS, Reid KJ, et al. Body mass index and mortality in acute myocardial infarction patients. Am J Med 2012;125:796-803. [Crossref] [PubMed]