Associations of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B With Cardiovascular Disease Occurrence in Adults: Korean Genome and Epidemiology Study.

Original Article Clinical Chemistry CROSSMARK_logo_3_Test 1/1 Ann Lab Med 2023;43:237-243 https://doi.org/10.3343/alm.2023.43.3.237 ISSN 2234-3806 • eISSN 2234-3814 https://crossmark-cdn.crossref.org/widget/v2.0/logos/CROSSMARK_Color_square.svg 2017-03-16 Associations of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B With Cardiovascular Disease Occurrence in Adults: Korean Genome and Epidemiology Study Shin Young Yun , M.D., John Hoon Rim , M.D., Hyein Kang , M.D., Sang-Guk Lee , M.D., and Jong-Baeck Lim , M.D. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea Background: Despite the superiority of non-HDL cholesterol (non-HDL-C) and apolipoprotein B (ApoB) as lipid markers for atherosclerotic cardiovascular disease (ASCVD), these are only suitable as secondary markers. We compared LDL cholesterol (LDL-C), non-HDLC, and ApoB concentrations with respect to the occurrence of cardiovascular disease in adults enrolled in the Korean Genome and Epidemiology Study (KoGES). Methods: We used information on age; sex; medical history; family history of ASCVD; current lipid-lowering therapy; current smoking status; and creatinine, total cholesterol, HDLC, LDL-C, triglyceride, and ApoB concentrations from 5,872 KoGES participants without ASCVD. New ASCVD development was monitored during the 8-year follow-up period. Adjusted hazard ratios (aHRs) for ASCVD of LDL-C, non-HDL-C, and ApoB concentrations were calculated based on the multivariate Cox regression analyses. The participants were also grouped as low and high according to the median values for each lipid marker, and calculated aHRs of each group combined by two lipid makers. Received: April 23, 2022 Revision received: September 11, 2022 Accepted: November 2, 2022 Corresponding author: Sang-Guk Lee, M.D., Ph.D. Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2228-2455 Fax: +82-2-2364-1583 E-mail: Results: ApoB showed the highest aHR per 1-SD for ASCVD (1.26; 95% confidence interval [CI], 1.11–1.43), followed by non-HDL-C (1.25; 95% CI, 1.11–1.41) and LDL-C (1.20; 95% CI, 1.06–1.37). The group with low LDL-C and high ApoB concentrations had a significantly higher aHR for ASCVD (1.61; 95% CI, 1.05–2.48) compared to the reference group values (low LDL-C and low ApoB concentrations). The aHR for the group with high LDL-C and low ApoB concentrations was not significant (1.30; 95% CI, 0.79–2.16). Conclusions: ApoB, non-HDL-C, and LDL-C are independent risk factors for ASCVD. Increases in the aHR per 1-SD for ASCVD were more strongly affected by ApoB, followed by non-HDL-C and LDL-C. Participants with low LDL-C and high ApoB concentrations showed increased ASCVD risk. For individuals with ASCVD risk factors, even those presenting normal LDL-C concentrations, measuring ApoB concentrations can provide useful information for better evaluation of ASCVD risk. Key Words: Atherosclerosis, LDL, Cholesterol, Apolipoprotein B INTRODUCTION The relationship between cholesterol concentration and atherosclerotic cardiovascular disease (ASCVD) has been studied for https://doi.org/10.3343/alm.2023.43.3.237 © Korean Society for Laboratory Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. several years. LDL, the dominant form of cholesterol, is considered an important risk factor for ASCVD. However, the risk of ASCVD remains even after lowering LDL cholesterol (LDL-C) to a normal concentration [1-3]. Other forms of cholesterol are asso- www.annlabmed.org  237 Yun SY, et al. Comparison of three lipid markers for ASCVD risk ciated with ASCVD, which are included in current global cholesterol guidelines [4, 5]. This increased the importance of nonHDL cholesterol (non-HDL-C) and apolipoprotein B (ApoB). NonHDL-C concentrations are calculated by subtracting the concentration of HDL-C from that of total cholesterol, comprising very low-density lipoprotein cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), remnant particles, lipoprotein (a) [Lp (a)], and LDL-C [6]. Not only LDL-C, all of them is known to play an important role in the atherosclerosis evolution. ApoB is the main protein found in VLDL-C, IDL-C, LDL-C, and Lp (a). Each of these lipoprotein particles includes a single ApoB protein; thus, measurement of ApoB concentrations indicates the number of ApoB-containing lipoproteins [7]. In most individuals, LDL-C, non-HDL-C, and ApoB concentrations correlate well; however, there is some discordance in individuals with hypertriglyceridemia, diabetes mellitus (DM), and metabolic syndrome [8]. Non-HDL-C and ApoB will increase with more cholesterol other than LDL-C, and ApoB will increase when the number of particles is high even if the cholesterol level is normal. However, discordance analysis has consistently shown that ASCVD risk follows lipid particle number and its surrogates rather than lipid cholesterol concentration [8]. It is known that the patients with DM are seemed to have smaller and more LDL particles than the other patients although LDL-C is not increased [9], which means higher ApoB concentration in the DM patients. According to 2019 ESC/ECS guidelines, ApoB, more than nonHDL-C, is recommended for risk assessment, particularly in people with high triglyceride levels, DM, obesity, or very low LDL-C concentrations [5]. Although studies have shown the superiority of non-HDL-C and ApoB as lipid markers for ASCVD [10-12], they are considered secondary markers [4, 5]. Both are recommended when LDL-C is very low or only in specific patient groups. In this study, as primary marker, LDL-C, non-HDL-C, and ApoB concentrations in participants of the Korean Genome and Epidemiology Study (KoGES) were compared with respect to the risk of cardiovascular disease. To our knowledge, this is the first Korean prospective cohort study exploring the association between ASCVD and lipid markers, including ApoB. MATERIALS AND METHODS Data distribution and selection Data from KoGES participants from 2001–2002 (baseline) to 2015–2016 (8th follow-up) were used in this study [13]. KoGES is an ongoing study that tracks patients’ medical history, labora- 238  www.annlabmed.org KoGES participants (N = 10,030) Third follow-up in 2007–2008 (N = 6,688) Excluded participants (N = 816) 386 for presence of ASCVD 148 for current lipid-lowering therapy 282 for no follow-up Eligible participants (N = 5,872) Fig. 1. Flow chart of participant selection. Abbreviation: KoGES, Korean Genome and Epidemiology Study; ASCVD, atherosclerotic cardiovascular disease. tory tests, and lifestyle every two years. All participants lived in Ansa (...truncated)