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
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 lo...
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| Published in | Circulation Journal Vol. 89; no. 8; pp. 1182 - 1189 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Japan
The Japanese Circulation Society
25.07.2025
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| Abstract | 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. |
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| AbstractList | 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. 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). 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 25 percentile 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. 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. 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).BACKGROUNDWe 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).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.METHODS AND RESULTSWe 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.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.CONCLUSIONSA 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. |
| ArticleNumber | CJ-24-0770 |
| Author | Masato Furuhashi Itaru Hosaka Marenao Tanaka Masafumi Inyaku Wataru Kawaharata Yukinori Akiyama Tatsuya Sato Keisuke Endo Kei Nakata Hiroki Aida Nagisa Hanawa |
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| Keywords | Ischemic heart disease Cardiovascular disease Small dense low-density lipoprotein cholesterol Coronary artery disease |
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| References_xml | – reference: 19. Tanaka M, Sato T, Endo K, Inyaku M, Mori K, Hosaka I, et al. An increase in calculated small dense low-density lipoprotein cholesterol predicts new onset of hypertension in a Japanese cohort. Hypertens Res 2023; 46: 2635–2645. – reference: 10. Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype: A proposed genetic marker for coronary heart disease risk. Circulation 1990; 82: 495–506. – reference: 30. de Graaf J, Swinkels DW, Demacker PN, de Haan AF, Stalenhoef AF. Differences in the low density lipoprotein subfraction profile between oral contraceptive users and controls. J Clin Endocrinol Metab 1993; 76: 197–202. – reference: 2. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42: 3227–3337. – reference: 8. Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002; 43: 1363–1379. – reference: 11. Krauss RM. Small dense low-density lipoprotein particles: Clinically relevant? Curr Opin Lipidol 2022; 33: 160–166. – reference: 35. Santos HO, Earnest CP, Tinsley GM, Izidoro LFM, Macedo RCO. Small dense low-density lipoprotein-cholesterol (sdLDL-C): Analysis, effects on cardiovascular endpoints and dietary strategies. Prog Cardiovasc Dis 2020; 63: 503–509. – reference: 22. Examination Committee of Criteria for ‘Obesity Disease’ in J, Japan Society for the Study of Obesity. New criteria for ‘obesity disease’ in Japan. Circ J 2002; 66: 987–992. – reference: 26. Hoogeveen RC, Gaubatz JW, Sun W, Dodge RC, Crosby JR, Jiang J, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: The Atherosclerosis Risk In Communities (ARIC) study. Arterioscler Thromb Vasc Biol 2014; 34: 1069–1077. – reference: 5. Kurobe M, Baba K, Nunohiro T, Ishizaki M, Furudono S, Nakata T, et al. Impact of implementation of a region-wide low-density lipoprotein cholesterol management clinical pathway for the secondary prevention of acute myocardial infarction. Circ J 2024; 88: 1825–1832. – reference: 34. Hayashi T, Koba S, Ito Y, Hirano T. Method for estimating high sdLDL-C by measuring triglyceride and apolipoprotein B levels. Lipids Health Dis 2017; 16: 21. – reference: 21. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: 982–992. – reference: 27. Tsai MY, Steffen BT, Guan W, McClelland RL, Warnick R, McConnell J, et al. New automated assay of small dense low-density lipoprotein cholesterol identifies risk of coronary heart disease: The Multi-ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 2014; 34: 196–201. – reference: 4. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111–188. – reference: 6. Maruo T, Ike A, Takamiya Y, Matsuoka Y, Shigemoto E, Kato Y, et al. Impact of controlling serum low-density lipoprotein cholesterol and triglycerides on long-term clinical outcomes in diabetic patients who have undergone percutaneous coronary intervention. Circ Rep 2024; 6: 573–582. – reference: 14. Sampson M, Ling C, Sun Q, Harb R, Ashmaig M, Warnick R, et al. A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia. JAMA Cardiol 2020; 5: 540–548. – reference: 23. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension Guidelines for the management of hypertension (JSH 2019). Hypertens Res 2019; 42: 1235–1481. – reference: 33. 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| Snippet | Background: We previously reported that a high level of small dense low-density lipoprotein cholesterol (sdLDL-C) calculated by the Sampson equation was... We previously reported that a high level of small dense low-density lipoprotein cholesterol (sdLDL-C) calculated by the Sampson equation was independently... |
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| SubjectTerms | 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 |
| Title | 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 |
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