High Level of Estimated Small Dense Low-Density Lipoprotein Cholesterol as an Independent Risk Factor for the Development of Ischemic Heart Disease Regardless of Low-Density Lipoprotein Cholesterol Level　― A 10-Year Cohort Study

• Published in: Circulation Journal Vol. 89; no. 8; pp. 1182 - 1189
• Main Authors: Endo, Keisuke, Tanaka, Marenao, Sato, Tatsuya, Inyaku, Masafumi, Nakata, Kei, Kawaharata, Wataru, Aida, Hiroki, Hosaka, Itaru, Akiyama, Yukinori, Hanawa, Nagisa, Furuhashi, Masato
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 25.07.2025
• Subjects: Adult; Aged; Cardiovascular disease; Cholesterol, LDL - blood; Cohort Studies; Coronary artery disease; Female; Follow-Up Studies; Humans; Ischemic heart disease; Japan - epidemiology; Male; Middle Aged; Myocardial Ischemia - blood; Myocardial Ischemia - epidemiology; Myocardial Ischemia - etiology; Risk Factors; Small dense low-density lipoprotein cholesterol; Japan; Ischemic heart disease; Cardiovascular disease; Small dense low-density lipoprotein cholesterol; Coronary artery disease
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-24-0770

Background: We previously reported that a high level of small dense low-density lipoprotein cholesterol (sdLDL-C) calculated by the Sampson equation was independently associated with the development of ischemic heart disease (IHD), but it remains unclear whether the effect depends on the level of low-density lipoprotein cholesterol (LDL-C).Methods and Results: We investigated the associations of new onset of IHD with categorized groups of high (H-) and low (L-) levels of estimated sdLDL-C and LDL-C using 25thpercentile levels of sdLDL-C level (25.2 mg/dL) and LDL-C (100 mg/dL) as cutoff values in 17,963 Japanese individuals (men/women: 11,508/6,455, mean age: 48 years) who underwent annual health checkups. During a 10-year follow-up period, 570 subjects (men/women: 449/121) had new development of IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, smoking habit, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) [95% confidence interval (CI)] for new onset of IHD was significantly higher in subjects with H-sdLDL-C/H-LDL-C (1.49 [1.06–2.08]) and subjects with H-sdLDL-C/L-LDL-C (1.49 [1.00–2.22]) than in subjects with L-sdLDL-C/L-LDL-C as the reference.Conclusions: A high level of sdLDL-C estimated by the Sampson equation was a predominant predictor for the development of IHD, regardless of the level of LDL-C, in a general Japanese population.