Endocrinology and Metabolism

Review Article

Diabetes, Obesity and Metabolism
Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia: Joon Ho Moon, Kyuho Kim, Sung Hee Choi; Endocrinol Metab. 2022;37(4):575-586. Published online August 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.402

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High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

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Monika I. Konaklieva, Balbina J. Plotkin
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Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the obesity medicine association and the National Lipid Association 2024
Harold Edward Bays, Carol Kirkpatrick, Kevin C. Maki, Peter P. Toth, Ryan T. Morgan, Justin Tondt, Sandra Michelle Christensen, Dave Dixon, Terry A. Jacobson
Obesity Pillars.2024; : 100108. CrossRef
Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review
Chaicharn Deerochanawong, Sin Gon Kim, Yu-Cheng Chang
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Xanthohumol, a prenylated chalcone, regulates lipid metabolism by modulating the LXRα/RXR-ANGPTL3-LPL axis in hepatic cell lines and high-fat diet-fed zebrafish models
Wan-Yun Gao, Pei-Yi Chen, Hao-Jen Hsu, Je-Wen Liou, Chia-Ling Wu, Ming-Jiuan Wu, Jui-Hung Yen
Biomedicine & Pharmacotherapy.2024; 174: 116598. CrossRef
Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024
Harold Edward Bays, Carol Kirkpatrick, Kevin C. Maki, Peter P. Toth, Ryan T. Morgan, Justin Tondt, Sandra Michelle Christensen, Dave Dixon, Terry A. Jacobson
Journal of Clinical Lipidology.2024;[Epub] CrossRef
High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
Franziska Schmalz, Janett Fischer, Hamish Innes, Stephan Buch, Christine Möller, Madlen Matz-Soja, Witigo von Schönfels, Benjamin Krämer, Bettina Langhans, Alexandra Klüners, Michael Soyka, Felix Stickel, Jacob Nattermann, Christian P. Strassburg, Thomas
JHEP Reports.2023; 5(4): 100684. CrossRef
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Dieter Lütjohann, Hans-Ulrich Klör, Frans Stellaard
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Influence of antipsychotic medications on hyperlipidemia risk in patients with schizophrenia: evidence from a population-based cohort study and in vitro hepatic lipid homeostasis gene expression
Tien-Yuan Wu, Ni Tien, Cheng-Li Lin, Yu-Cun Cheah, Chung Y. Hsu, Fuu-Jen Tsai, Yi-Jen Fang, Yun-Ping Lim
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Alejandro Gugliucci
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Dyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview
Sang Heon Suh, Soo Wan Kim
Diabetes & Metabolism Journal.2023; 47(5): 612. CrossRef
Peroxisome Proliferator-Activated Receptor α in Lipoprotein Metabolism and Atherosclerotic Cardiovascular Disease
Elena Valeria Fuior, Evangelia Zvintzou, Theodosios Filippatos, Katerina Giannatou, Victoria Mparnia, Maya Simionescu, Anca Violeta Gafencu, Kyriakos E. Kypreos
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Scientific Reports.2023;[Epub] CrossRef

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association of High-Density Lipoprotein Cholesterol Phenotypes with the Risk of Cardiovascular Diseases and Mortality: A Cohort Study in Korea: Ga Eun Nam, Youn Huh, Jin-Hyung Jung, Kyungdo Han, Seon Mee Kim, on Behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity; Endocrinol Metab. 2022;37(2):261-271. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1259

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Background
We investigated whether low high-density lipoprotein cholesterol (HDL-C) and isolated and non-isolated low HDL-C levels are associated with the risk of cardiovascular diseases and all-cause mortality among Korean adults.
Methods
We included 8,665,841 individuals aged ≥20 years who had undergone a health examination provided by the Korean National Health Insurance Service (NHIS) in 2009 and were followed up until the end of 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for study outcomes were calculated using multivariable Cox proportional hazard regression analysis.
Results
During the 8.2 years of mean follow-up, myocardial infarction (MI), stroke, and all-cause mortality occurred in 81,431, 110,996, and 244,309 individuals, respectively. After adjusting for confounding variables (model 3), individuals with low HDL-C and lower HDL quartiles were associated with significantly increased risks of all three outcomes, compared to those with normal HDL-C and highest HDL-C quartile (all P<0.001), respectively. HRs for incident MI (1.28; 95% CI, 1.26 to 1.30), stroke (1.13; 95% CI, 1.11 to 1.15), and all-cause mortality (1.07; 95% CI, 1.05 to 1.08) increased in the non-isolated low HDL-C group compared to the normal HDL-C group. Isolated low HDL-C also showed an increase in the HRs of incident stroke (1.06; 95% CI, 1.04 to 1.08) and all-cause mortality (1.30; 95% CI, 1.28 to 1.32).
Conclusion
Low HDL-C and non-isolated low HDL-C were associated with increased risk of MI, stroke, and all-cause mortality, and isolated low HDL-C was associated with incident stroke and all-cause mortality risk.

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Association between HDL levels and stroke outcomes in the Arab population
Aizaz Ali, Omar Obaid, Naveed Akhtar, Rahul Rao, Syed Haroon Tora, Ashfaq Shuaib
Scientific Reports.2024;[Epub] CrossRef
Association of adiposity and fitness with triglyceride-to-high-density lipoprotein cholesterol ratio in youth
Danladi Ibrahim Musa, Abel Lamina Toriola, Nurudeen O Abubakar, Sunday Omachi, Victor B Olowoleni, Kolade B Ayodele
Annals of Pediatric Cardiology.2023; 16(3): 194. CrossRef
Association between cholesterol levels and dementia risk according to the presence of diabetes and statin use: a nationwide cohort study
You-Bin Lee, Min Young Kim, Kyungdo Han, Bongsung Kim, Jiyun Park, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Sang-Man Jin
Scientific Reports.2022;[Epub] CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea: Jinyoung Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2022;37(2):303-311. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1332

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Background
High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer.
Methods
The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models.
Results
A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126).
Conclusion
Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.

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Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer
Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
Scientific Reports.2024;[Epub] CrossRef
Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013–2014 National Health and Nutrition Examination Survey
Fu-Jen Cheng, Kai-Fan Tsai, Kuo-Chen Huang, Chia-Te Kung, Wan-Ting Huang, Huey-Ling You, Shau-Hsuan Li, Chin-Chou Wang, Wen-Chin Lee, Hsiu-Yung Pan
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Low serum total cholesterol levels predict inferior prognosis of patients with POEMS syndrome
Jue Zhang, Ting Zhang, Ye Yao, Xuxing Shen, Yuanyuan Jin, Run Zhang, Lijuan Chen
Discover Oncology.2024;[Epub] CrossRef
Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field
Michal Olejarz, Ewelina Szczepanek-Parulska, Marek Ruchala
Frontiers in Endocrinology.2024;[Epub] CrossRef
Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort
Xue Xiao, Yi Huang, Fetemeh Sadeghi, Maria Feychting, Niklas Hammar, Fang Fang, Zhe Zhang, Qianwei Liu
Cancers.2023; 15(2): 520. CrossRef
Altered serum lipid levels are associated with prognosis of diffuse large B cell lymphoma and influenced by utility of rituximab
Fei Wang, Luo Lu, HuiJuan Chen, Yanhua Yue, Yanting Sun, Feng Yan, Bai He, Rongrong Lin, Weiying Gu
Annals of Hematology.2023; 102(2): 393. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
High-density lipoprotein cholesterol and carcinogenesis
Meijuan Tan, Shijie Yang, Xiequn Xu
Trends in Endocrinology & Metabolism.2023; 34(5): 303. CrossRef
Low Serum Cholesterol Level Is a Significant Prognostic Factor That Improves CLL-IPI in Chronic Lymphocytic Leukaemia
Rui Gao, Kaixin Du, Jinhua Liang, Yi Xia, Jiazhu Wu, Yue Li, Bihui Pan, Li Wang, Jianyong Li, Wei Xu
International Journal of Molecular Sciences.2023; 24(8): 7396. CrossRef
Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study
Weiwei Liang, FangFang Sun
Frontiers in Endocrinology.2023;[Epub] CrossRef
Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: a Mendelian randomization study
Qiang Ma, Yu Li, Lijuan An, Liang Guo, Xiaokang Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Risk factors and diagnostic prediction models for papillary thyroid carcinoma
Xiaowen Zhang, Yuyang Ze, Jianfeng Sang, Xianbiao Shi, Yan Bi, Shanmei Shen, Xinlin Zhang, Dalong Zhu
Frontiers in Endocrinology.2022;[Epub] CrossRef
Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: A case-control study
Jia-liu He, Hua-bing Wu, Wen-lei Hu, Jian-jun Liu, Qian Zhang, Wei Xiao, Ming-jun Hu, Ming Wu, Fen Huang
International Journal of Hygiene and Environmental Health.2022; 246: 114049. CrossRef

Diabetes, Obesity and Metabolism
Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat: Sun Ok Song, You-Cheol Hwang, Han Uk Ryu, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko; Endocrinol Metab. 2021;36(4):835-844. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1130

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Background
Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.
Methods
All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.
Results
A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm² in men and 63.1±39.5 cm² in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.
Conclusion
These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

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Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Metabolism.2022; 137: 155327. CrossRef
The associations between lipid profiles and visceral obesity among gastrointestinal cancer patients: a cross-sectional study
Bo Gao, Xiangrui Li, Wenqing Chen, Shu’an Wang, Jian He, Yu Liu, Chao Ding, Xiaotian Chen
Lipids in Health and Disease.2022;[Epub] CrossRef

Adrenal Gland
Lipid Profiles in Primary Aldosteronism Compared with Essential Hypertension: Propensity-Score Matching Study: Sun Joon Moon, Han Na Jang, Jung Hee Kim, Min Kyong Moon; Endocrinol Metab. 2021;36(4):885-894. Published online August 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.1012

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Background
There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function.
Methods
Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively.
Results
Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed.
Conclusion
PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

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Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups
Kaiwen Sun, Minghui Gong, Yang Yu, Minghui Yang, Ying Zhang, Yinong Jiang, Wei Song
Frontiers in Endocrinology.2024;[Epub] CrossRef
Meta‐analysis of blood parameters related to lipid and glucose metabolism between two subtypes of primary aldosteronism
Qiu‐Gen Zhu, Feng Zhu
The Journal of Clinical Hypertension.2023; 25(1): 13. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
The differences of serum lipid profiles between primary aldosteronism and essential hypertension: a meta-analysis and systematic review
Worapaka Manosroi, Pitchaporn Phudphong, Pichitchai Atthakomol, Mattabhorn Phimphilai
BMC Endocrine Disorders.2022;[Epub] CrossRef

Clinical Study
Efficacy and Safety of Pitavastatin in a Real-World Setting: Observational Study Evaluating SaFety in Patient Treated with Pitavastatin in Korea (PROOF Study): In-Kyung Jeong, Sung-Rae Kim; Endocrinol Metab. 2020;35(4):882-891. Published online December 2, 2020; DOI: https://doi.org/10.3803/EnM.2020.723

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Background
While randomized controlled trials provide useful information about drug safety and efficacy, they do not always reflect the observed results in the real world. The prospective, observational, non-comparative trial in South Korea was designed to evaluate the efficacy and safety of pitavastatin in clinical practice in 28,343 patients.
Methods
This study was conducted in 893 facilities in Korea from April 2, 2012 to April 1, 2017. This study was designed to administer 1, 2, or 4 mg pitavastatin to patients with hyperlipidemia at the age of 20 or older for at least 8 weeks.
Results
For 126 days of mean duration of administration of pitavastatin, the % change of low density lipoprotein cholesterol indicated a dose dependent reduction: –23.4%, –29.1%, and –35.2% in the 1, 2, and 4 mg groups, respectively in patients who have not been treated with lipid lowering medications prior to study. Only 1.74% (492/28,343) of pitavastatin-treated patients experienced adverse events, of which 0.43% (123/28,343) were adverse drug reactions. Less than 1% of patients experienced the grade 2 or more toxicity (Common Terminology Criteria for Adverse Events v4.03) in alanine aminotransferase, aspartate aminotransferase, serum creatinine, and serum creatine phosphokinase. Although there were no rhabdomyolysis in 28,343 patients, 0.04% of patients had been reported pitavastatin-related musculoskeletal disorders.
Conclusion
Overall, this observational study showed that pitavastatin was well tolerated and effectively modified the lipid profile, reducing cardiovascular and cerebrovascular risk in Korean patients with hypercholesterolemia in the real world.

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Low-Density Lipoprotein Cholesterol Level, Statin Use and Myocardial Infarction Risk in Young Adults
Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
Journal of Lipid and Atherosclerosis.2022; 11(3): 288. CrossRef

Clinical Study
Achievement of LDL-C Targets Defined by ESC/EAS (2011) Guidelines in Risk-Stratified Korean Patients with Dyslipidemia Receiving Lipid-Modifying Treatments: Ye Seul Yang, Seo Young Lee, Jung-Sun Kim, Kyung Mook Choi, Kang Wook Lee, Sang-Chol Lee, Jung Rae Cho, Seung-Jin Oh, Ji-Hyun Kim, Sung Hee Choi; Endocrinol Metab. 2020;35(2):367-376. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.367

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Background
This study assessed the proportion of risk-stratified Korean patients with dyslipidemia achieving their low-density lipoprotein cholesterol (LDL-C) targets as defined by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) (2011) guidelines while receiving lipid-modifying treatments (LMTs).
Methods
In this multicenter, cross-sectional, observational study, we evaluated data from Korean patients aged ≥19 years who were receiving LMTs for ≥3 months and had an LDL-C value within the previous 12 months on the same LMT. Data were collected for demographics, cardiovascular (CV) risk factors, medical history, and healthcare consumption. Patients were risk-stratified according to the ESC Systematic COronary Risk Evaluation (SCORE) chart and LDL-C target achievement rate was assessed.
Results
Guideline-based risk-stratification of the 1,034 patients showed the majority (72.2%) to be in the very high-risk category. Investigators’ assessment of risk was underestimated in 71.6% compared to ESC/EAS guidelines. Overall LDL-C target achievement rate was 44.3%; target achievement was the highest (66.0%) in moderate-risk patients and the lowest (39.0%) in very high-risk patients. Overall 97.1% patients were receiving statin therapy, mostly as a single-agent (89.2%). High-intensity statins and the highest permissible dose of high-intensity statins had been prescribed to only 9.1% and 7.3% patients in the very high-risk group, respectively. Physician satisfaction with patients’ LDL-C levels was the primary reason for non-intensification of statin therapy.
Conclusion
Achievement of target LDL-C level is suboptimal in Korean patients with dyslipidemia, especially in those at very high-risk of CV events. Current practices in LMTs need to be improved based on precise CV risk evaluation posed by dyslipidemia.

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Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Journal of Lipid and Atherosclerosis.2023; 12(1): 12. CrossRef
Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Diabetes & Metabolism Journal.2023; 47(1): 1. CrossRef
Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion
Jagdish Hiremath, J C Mohan, Prakash Hazra, JP S Sawhney, Ashwani Mehta, Sadanand Shetty, Abraham Oomman, Mahesh K Shah, Ganapathi Bantwal, Rajeev Agarwal, Rajiv Karnik, Peeyush Jain, Saumitra Ray, Sambit Das, Vibhuti Jadhao, Sachin Suryawanshi, Hanmant B
Cureus.2023;[Epub] CrossRef
Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study
Julia Brandts, Sarah Bray, Guillermo Villa, Alberico L. Catapano, Neil R. Poulter, Antonio J. Vallejo-Vaz, Kausik K. Ray
The Lancet Regional Health - Europe.2023; 31: 100665. CrossRef
Management of Dyslipidemia in Patients with Diabetes Mellitus
Kyung Ae Lee
The Journal of Korean Diabetes.2023; 24(3): 111. CrossRef
Target Low-Density Lipoprotein-Cholesterol and Secondary Prevention for Patients with Acute Myocardial Infarction: A Korean Nationwide Cohort Study
Ju Hyeon Kim, Jung-Joon Cha, Subin Lim, Jungseok An, Mi-Na Kim, Soon Jun Hong, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Do-Sun Lim, Kyeongmin Byeon, Sang-Wook Kim, Eun-Seok Shin, Kwang Soo Cha, Jei Keon Chae, Youngkeun Ahn, Myung Ho Jeong, Tae Hoo
Journal of Clinical Medicine.2022; 11(9): 2650. CrossRef
Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sung
Diabetes & Metabolism Journal.2022; 46(3): 464. CrossRef
There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness
Michael E. Makover, Michael D. Shapiro, Peter P. Toth
American Journal of Preventive Cardiology.2022; 12: 100371. CrossRef
Non-achievement of the Low-Density Lipoprotein Cholesterol Goal in Older Patients with Type 2 Diabetes Mellitus and a Very High Cardiovascular Disease Risk: A Multicenter Study in Vietnam
Huan Thanh Nguyen, Khang Pham Trong Ha, An Huu Nguyen, Thu Thanh Nguyen, Hang My Lam
Annals of Geriatric Medicine and Research.2021; 25(4): 278. CrossRef

Clinical Study
Effects of a Portfolio-Mediterranean Diet and a Mediterranean Diet with or without a Sterol-Enriched Yogurt in Individuals with Hypercholesterolemia: Yvelise Ferro, Elisa Mazza, Mariantonietta Salvati, Emma Santariga, Salvatore Giampà, Rocco Spagnuolo, Patrizia Doldo, Roberta Pujia, Adriana Coppola, Carmine Gazzaruso, Arturo Pujia, Tiziana Montalcini; Endocrinol Metab. 2020;35(2):298-307. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.298

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Background
A growing number of functional foods have been proposed to reduce cholesterol levels and the Portfolio Diet, which includes a combination of plant sterols, fibres, nuts, and soy protein, reduces low density lipoprotein cholesterol (LDL-C) from 20% to 30% in individuals with hyperlipidaemia. In this pilot study, the aim was to investigate whether a Mediterranean Diet incorporating a new and simple combination of cholesterol-lowering foods, excluding soy and nuts (namely the Portfolio-Mediterranean Diet), would reduce LDL-C levels, in the short-term, better than a Mediterranean Diet plus a sterol-enriched yogurt or a Mediterranean Diet alone.
Methods
We retrospectively evaluated 24 individuals on a Portfolio-Mediterranean Diet and 48 matched individuals on a Mediterranean Diet with or without a sterol-enriched yogurt (24 each groups) as controls.
Results
At follow-up (after 48±12 days), we observed an LDL reduction of 21±4, 23±4, and 44±4 mg/dL in the Mediterranean Diet alone, Mediterranean Diet plus yogurt and Portfolio-Mediterranean Diet respectively (P<0.001).
Conclusion
A Portfolio-Mediterranean Diet, incorporating a new combination of functional foods such as oats or barley, plant sterols, chitosan, and green tea but not soy and nuts, may reduce LDL of 25% in the short term in individuals with hypercholesterolemia.

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Efficacy of Fluvastatin in Patients with Hypercholesterolemia.: Moon Ho Kang, Sung Gwang Lee, Jung Ho Youn, Tae Suk Kim, Seung Woon Ahn; J Korean Endocr Soc. 1996;11(1):75-84. Published online November 7, 2019

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Abstract PDF: Background
Fluvastatin is the first entirely synthetic 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA) reductase inhibitor. Clinical data indicate that this agent exhibits the proven efficacy of its class and also has some theoretical advantages in safety for long-term use because of its unique pharmacololgic property consistent with hepatoselectivity(i.e., low systemic exposure). This study is to evaluate efficacy and safety of fluvastatin in hypercholesterolemic patients in Korea. Methods: An open clinical trial with fluvastatin was conducted in 31 subjects who continued to have high blood cholesterol levels of 6.21 mmol/L(240 mg/dl) or greater after 1 month of lipid-lowering diet plus single blind placebo period. Fluvastatin was administered for 8 weeks with the initial dose of 20 mg per day and if serum cholesterol levels did not fall below 5.20 mmol/L(200 mg/dl) after 4 weeks the dose was increased to 40 mg per day for the second 4 weeks. On each visit every 4 weeks they underwent interview and laboratory tests about side effects and tolerability. Results: The mean % changes in plasma total cholesterol and LDL-cholesterol from baseline were -14.6% and -20.2% at 4 week, and -19.5% and -24.7% at 8 week respectively(p<0.001). No significant change in plasma triglyceride was found in the overall group, but when analysis is confined to those with hypertriglycedemia combined(TG>- 2.26 mmol/L or 200 mg/dl), plasma triglyceride levels were significantly reduced by 23.3% at 8 week(p<0.05). There was no significant change in HDL-cholesterol during fluvastatin treatment. Three patients had mild gastrointestinal symptoms and one patient developed drowsiness, no symptoms were severe enough to discontinue the medication. Notable laboratory abnormalities including serum transaminase and creatine kinase elevations were not observed. Conclusion: This study suggests that fluvastatin is an effective, safe, and well-tolerated lipid lowering agent in the treatment of hypercholesterolemia. Controlled clinical studies on large scale and long-term basis should be followed.

Review Articles

The Role of Macrophage Lipophagy in Reverse Cholesterol Transport: Se-Jin Jeong, Mi-Ni Lee, Goo Taeg Oh; Endocrinol Metab. 2017;32(1):41-46. Published online March 20, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.41

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Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

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Prevalence and Clinical Characteristics of Dyslipidemia in Koreans: Jee-Sun Jeong, Hyuk-Sang Kwon; Endocrinol Metab. 2017;32(1):30-35. Published online March 20, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.30

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The prevalence of hypercholesterolemia in Koreans 30 years old and over was 19.5% in 2015 according to the Korean Nutrition and Health Examination Survey, which means that one-fifth of adults had hypercholesterolemia. The prevalence of hypertriglyceridemia in adults 30 years of age and older was 16.8% in 2015, and men had a 2-fold higher prevalence of hypertriglyceridemia than women (23.9% vs. 10.4%). The awareness of hypercholesterolemia in Koreans was higher in women than among men (62.4% vs. 51.4%). It increased with age; the level of awareness in participants 30 to 49 years of age (32.1% in men and 32.6% in women) was less than half of that observed among respondents ≥65 years old (77.5% in men and 78.0% in women). Regular check-ups for dyslipidemia and the active management thereof are urgent in Korean men aged 30 to 49. In women, the perimenopausal period is crucial for the prevention and management of metabolic syndrome, including dyslipidemia. Overall, improvements in awareness and treatment in the age group of 30 to 49 years in both men and women remain necessary.

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Original Article

Clinical Study
Eligibility for Statin Treatment in Korean Subjects with Reduced Renal Function: An Observational Study: Byung Sub Moon, Jongho Kim, Ji Hyun Kim, Young Youl Hyun, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Kyu-Beck Lee, Hyang Kim, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(3):402-409. Published online August 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.402

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Background

The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults.

Methods

Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m²; stage 2, eGFR 60 to 89 mL/min/1.73 m²; and stages 3 to 5, eGFR <60 mL/min/1.73 m². Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD) was calculated using the Framingham Risk Score (FRS) and Pooled Cohort Equation (PCE).

Results

There were 3,546 (18.9%) and 4,048 (21.5%) statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO) recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD) (κ value, 0.689 vs. 0.531). When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined.

Conclusions

The proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD.

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Frontiers of Medicine.2019; 13(6): 713. CrossRef
Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea
Y. J. Jeong, H. Kim, S. J. Baik, T. M. Kim, S. J. Yang, S.-H. Lee, J.-H. Cho, H. Lee, H. W. Yim, I. Y. Choi, K.-H. Yoon, H.-S. Kim
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Comparison between Atorvastatin and Rosuvastatin in Renal Function Decline among Patients with Diabetes
Eugene Han, Gyuri Kim, Ji-Yeon Lee, Yong-ho Lee, Beom Seok Kim, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
Endocrinology and Metabolism.2017; 32(2): 274. CrossRef

Review Article

Obesity and Metabolism
High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis: Alice Ossoli, Chiara Pavanello, Laura Calabresi; Endocrinol Metab. 2016;31(2):223-229. Published online June 10, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.223

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Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system.

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Original Articles

Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

Citations

Citations to this article as recorded by

Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
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Loperamide induces excessive accumulation of bile acids in the liver of mice with different diets
Zili Lei, Hedong Rong, Yanhong Yang, Siping Yu, Tianle Zhang, Lei Chen, Ya Nie, Qi Song, Qing Hu, Jiao Guo
Toxicology.2022; 477: 153278. CrossRef
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Giuseppe Ferrandino, Rachel R. Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J. Perry, Rebecca Cardone, Richard G. Kibbey, Gerald I. Shulman, Vishwa Deep Dixit, Nancy Carrasco
Proceedings of the National Academy of Sciences.2017;[Epub] CrossRef

APOA5 Polymorphism Is Associated with Metabolic Syndrome in Korean Postmenopausal Women.: Doh Hee Kim, Seung Hee Lee, Kyung Hoon Han, Chae Bong Kim, Kwan Young Song, Sook Cho, Kye Heui Lee; Endocrinol Metab. 2012;27(4):276-281. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.276

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Abstract PDF

BACKGROUND
Menopause is an independent risk factor in metabolic syndrome which induced an alteration of the lipid metabolism by hormonal changes. Apolipoprotein A5 gene (APOA5) was related to the regulation of triglyceride and high density lipoprotein cholesterol (HDL-C) level with biosynthesis and decomposition. This study was conducted to investigate the relationship between APOA5 polymorphism and metabolic syndrome in Korean postmenopausal women. METHODS: This study included 307 postmenopausal women with anthropometric and biochemical measurement in 2010-2011. The polymorphism of APOA5 was analyzed by polymerase chain reaction-restriction fragment length polymorphism method with MseI restriction enzyme. RESULTS: The metabolic syndrome prevalence with TT genotype was significantly lower than the frequency in those with TC/CC (27.09%, 38.46%, and 45.71% for TT, TC, and CC, respectively; P < 0.05). Multiple regression analysis of metabolic syndrome risk factors indicated that postmenopausal women with CC genotype had a higher risk with 3 times than that in TT genotype (P < 0.05). APOA5 C carriers showed an increased risk of triglyceride level (odd ratio, 2.93 and 1.85 for CC and TC+CC, respectively; P < 0.05). Interestingly, HDL-C was related to triglyceride directly in comparison to APOA5. CONCLUSION: The results of this study indicate that APOA5 has an influence on serum triglyceride and HDL-C, which contribute to metabolic syndrome in Korean postmenopausal women.

Citations

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Effects of a 3-year dietary intervention on age-related changes in triglyceride and apolipoprotein A-V levels in patients with impaired fasting glucose or new-onset type 2 diabetes as a function of the APOA5 -1131 T > C polymorphism
Minjoo Kim, Jey Sook Chae, Miri Kim, Sang-Hyun Lee, Jong Ho Lee
Nutrition Journal.2014;[Epub] CrossRef
APOA5Polymorphism Is Associated with Metabolic Syndrome in Korean Postmenopausal Women
Mi Hae Seo, Won Young Lee
Endocrinology and Metabolism.2012; 27(4): 274. CrossRef

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