Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD

Changhyun Lee; Jung Tak Park; Tae Ik Chang; Ea Wha Kang; Ki Heon Nam; Young Su Joo; Su Ah Sung; Yeong Hoon Kim; Dong Wan Chae; Su Kyung Park; Curie Ahn; Kook Hwan Oh; Tae Hyun Yoo; Shin Wook Kang; Seung Hyeok Han

doi:10.1016/j.numecd.2021.09.037

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD

Changhyun Lee, Jung Tak Park, Tae Ik Chang, Ea Wha Kang, Ki Heon Nam, Young Su Joo, Su Ah Sung, Yeong Hoon Kim, Dong Wan Chae, Su Kyung Park, Curie Ahn, Kook Hwan Oh, Tae Hyun Yoo, Shin Wook Kang, Seung Hyeok Han

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Background and aims: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and results: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. Conclusions: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

Original language	English
Pages (from-to)	410-419
Number of pages	10
Journal	Nutrition, Metabolism and Cardiovascular Diseases
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.numecd.2021.09.037
Publication status	Published - 2022 Feb

Bibliographical note

Funding Information:
This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention (2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, and 2016E3300200). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.The authors acknowledge the following participating clinical centers: Seoul National University Hospital (1104-089-359), Seoul National University Bundang Hospital (B-1106/129-008), Yonsei University Severance Hospital (4-2011-0163), Kangbuk Samsung Medical Center (2011-01-076), Seoul St. Mary's Hospital (KC11OIMI0441), Gil Hospital (GIRBA2553), Eulji General Hospital (201105-01), Chonnam National University Hospital (CNUH-2011-092), and Pusan Paik Hospital (11-091) in 2011.

Funding Information:
This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention ( 2011E3300300 , 2012E3301100 , 2013E3301600 , 2013E3301601 , 2013E3301602 , and 2016E3300200 ). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Publisher Copyright:
© 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University

All Science Journal Classification (ASJC) codes

Medicine (miscellaneous)
Endocrinology, Diabetes and Metabolism
Nutrition and Dietetics
Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.numecd.2021.09.037

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Lee, C., Park, J. T., Chang, T. I., Kang, E. W., Nam, K. H., Joo, Y. S., Sung, S. A., Kim, Y. H., Chae, D. W., Park, S. K., Ahn, C., Oh, K. H., Yoo, T. H., Kang, S. W., & Han, S. H. (2022). Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD. Nutrition, Metabolism and Cardiovascular Diseases, 32(2), 410-419. https://doi.org/10.1016/j.numecd.2021.09.037

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title = "Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD",

abstract = "Background and aims: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and results: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. Conclusions: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.",

author = "Changhyun Lee and Park, {Jung Tak} and Chang, {Tae Ik} and Kang, {Ea Wha} and Nam, {Ki Heon} and Joo, {Young Su} and Sung, {Su Ah} and Kim, {Yeong Hoon} and Chae, {Dong Wan} and Park, {Su Kyung} and Curie Ahn and Oh, {Kook Hwan} and Yoo, {Tae Hyun} and Kang, {Shin Wook} and Han, {Seung Hyeok}",

note = "Funding Information: This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention (2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, and 2016E3300200). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.The authors acknowledge the following participating clinical centers: Seoul National University Hospital (1104-089-359), Seoul National University Bundang Hospital (B-1106/129-008), Yonsei University Severance Hospital (4-2011-0163), Kangbuk Samsung Medical Center (2011-01-076), Seoul St. Mary's Hospital (KC11OIMI0441), Gil Hospital (GIRBA2553), Eulji General Hospital (201105-01), Chonnam National University Hospital (CNUH-2011-092), and Pusan Paik Hospital (11-091) in 2011. Funding Information: This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention ( 2011E3300300 , 2012E3301100 , 2013E3301600 , 2013E3301601 , 2013E3301602 , and 2016E3300200 ). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University",

year = "2022",

month = feb,

doi = "10.1016/j.numecd.2021.09.037",

language = "English",

volume = "32",

pages = "410--419",

journal = "Nutrition, Metabolism and Cardiovascular Diseases",

issn = "0939-4753",

publisher = "Elsevier",

number = "2",

}

Lee, C, Park, JT, Chang, TI, Kang, EW, Nam, KH, Joo, YS, Sung, SA, Kim, YH, Chae, DW, Park, SK, Ahn, C, Oh, KH, Yoo, TH , Kang, SW & Han, SH 2022, 'Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD', Nutrition, Metabolism and Cardiovascular Diseases, vol. 32, no. 2, pp. 410-419. https://doi.org/10.1016/j.numecd.2021.09.037

TY - JOUR

T1 - Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease

T2 - Results from the KNOW-CKD

AU - Lee, Changhyun

AU - Park, Jung Tak

AU - Chang, Tae Ik

AU - Kang, Ea Wha

AU - Nam, Ki Heon

AU - Joo, Young Su

AU - Sung, Su Ah

AU - Kim, Yeong Hoon

AU - Chae, Dong Wan

AU - Park, Su Kyung

AU - Ahn, Curie

AU - Oh, Kook Hwan

AU - Yoo, Tae Hyun

AU - Kang, Shin Wook

AU - Han, Seung Hyeok

N1 - Funding Information: This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention (2011E3300300, 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, and 2016E3300200). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.The authors acknowledge the following participating clinical centers: Seoul National University Hospital (1104-089-359), Seoul National University Bundang Hospital (B-1106/129-008), Yonsei University Severance Hospital (4-2011-0163), Kangbuk Samsung Medical Center (2011-01-076), Seoul St. Mary's Hospital (KC11OIMI0441), Gil Hospital (GIRBA2553), Eulji General Hospital (201105-01), Chonnam National University Hospital (CNUH-2011-092), and Pusan Paik Hospital (11-091) in 2011. Funding Information: This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention ( 2011E3300300 , 2012E3301100 , 2013E3301600 , 2013E3301601 , 2013E3301602 , and 2016E3300200 ). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University

PY - 2022/2

Y1 - 2022/2

N2 - Background and aims: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and results: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. Conclusions: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

AB - Background and aims: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of “the lower, the better” strategy for statin intake. Methods and results: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70–99, 100–129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70–99, 100–129, and ≥130 mg/dL were 2.06 (1.14–3.73), 2.79 (1.18–6.58), and 4.10 (1.17–14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. Conclusions: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

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DO - 10.1016/j.numecd.2021.09.037

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SN - 0939-4753

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EP - 419

JO - Nutrition, Metabolism and Cardiovascular Diseases

JF - Nutrition, Metabolism and Cardiovascular Diseases

IS - 2

ER -

Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD

Abstract

Bibliographical note

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UN SDGs

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