Prognostic significance of baseline low-density lipoprotein cholesterol in patients undergoing coronary revascularization; A report from the CREDO-Kyoto registry

Background The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear. Therefore, we aimed to investigate the baseline characteristics and clinical outcomes of patients with low baseline LDL-C levels who had undergone coronary revascularization. Methods We enrolled 39439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. After excluding 6306 patients with missing baseline LDL-C data, the study population consisted of 33133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels. Results Patients in the very low LDL-C quintile (< 85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4%, low: 14.5%, intermediate: 11.1%, high: 10.0%, and very high:9.2%; P<0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95% CI 1.16-1.44, P<0.001; low: HR 1.15, 95% CI 1.03-1.29, P=0.01). There were no significant interactions between the association of LDL-C level with all-cause death and subgroup factors, such as lipid-lowering treatment at index hospitalization, age, sex, acute myocardial infarction presentation, and study cohort. The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95% CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95% CI 1.15-1.60), sudden death (HR 1.44, 95% CI 1.01-2.06), and heart failure admission (HR 1.11 95% CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke. Conclusions Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial none ### Funding Statement This study was supported by an educational grant from the Research Institute for Production Development (Kyoto, Japan). Dr Yamaji has received a research grant from Abbott Vascular. Dr Shiomi has received honoraria from Abbott Vascular and Boston Scientific. Dr Morimoto has received lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; and has served on the Advisory Board of Sanofi. Dr Ehara has received honoraria from Abbott Vascular, Bayer, Boston Scientific, Medtronic, and Terumo. Dr Furukawa has received honoraria from Bayer, Kowa, and Sanofi. Dr Nakagawa has received research grants from Abbott Vascular and Boston Scientific; and honoraria from Abbott Vascular, Bayer, and Boston Scientific. Dr Kimura has received a research grant from Abbott Vascular; and honoraria from Astellas, AstraZeneca, Bayer, Boston Scientific, Kowa, and Sanofi. All the other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research protocol of the CREDO-Kyoto Cohort-3 was approved by the Institutional Review Board of Kyoto University (E2400) and by the local ethics committees of all participating medical centers. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The deidentified participant data will not be shared.