Editorial
Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) on Lipid Metabolism and Insulin Resistance in Human
2021 年 28 巻 4 号 p. 317-318
詳細
2021 年 28 巻 4 号 p. 317-318
See article vol. 28: 329-337
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is recognized as a key factor of familial hypercholesterolemia since 2003 1) . Afterward, the association of PCSK9 genetic variance was found with low-density lipoprotein (LDL) cholesterol level and risk of coronary heart disease (CHD) 2) , and PCSK9 has been a novel therapeutic target. Recently, two monoclonal antibodies to PCSK9 (Evolocumab and Airocumab) have been available especially for high cholesterol patients resistant to statins and other lipid-lowering medication, and clinical and research interests are increasing on PCSK9. Although PCSK9 has a vital role in lipid metabolism and CHD risk, the interpretation of serum PCSK9 level remains not well known.
Presently, Hamamura et al. examined the association of serum PCSK9 levels with lipid metabolism and insulin resistance in the Japanese general population with a cross-sectional study design 3) . Higher serum PCSK9 level was associated with serum levels of triglycerides and lipoprotein(a) and insulin resistance among the Japanese population that has relatively low CHD risk. Regarding serum LDL cholesterol levels, a positive association was not observed in univariate linear regression analysis among the overall population. However, this finding did not deny a positive association between serum PCSK9 level and LDL cholesterol level in the general population because the beta coefficient of serum LDL cholesterol level in relation to serum PCSK9 level was quite similarly positive among both individuals who were using lipid-lowering medication and those who were not using such medication. The current research provides a clue for the interpretation of the high serum PCSK9 level.
To my knowledge, only one study examines the association between serum PCSK9 levels and the risk of cardiovascular disease (CVD). Among 4,232 Swedish men and women aged 60 years with 485 ischemic CVD events during 15 years of follow-up, serum PCSK9 levels were linearly positively associated with incident ischemic CVD including myocardial infarction, angina pectoris, chronic CHD, sudden cardiac death, and ischemic stroke 4) . Although Swedish population has generally higher CVD risk than Japanese population 5) , serum PCSK9 level was not higher in the Swedish study (median level: 94.3 ng/ml measured with ELISA) 4) than that in the Japanese population (mean level: 211.2 ng/ml measured with ELISA) 3) . In a Kenyan study with 698 middle-aged adults which reported the positive association of serum PCSK9 level with hepatic enzyme levels and fatty liver disease, serum PCSK9 level was approximately 150 ng/ml in the median 6) . These findings suggest that there may be racial differences on serum PCSK9 levels.
Furthermore, from a meta-analysis of previous intervention studies, moderate-to-vigorous physical activities increase plasma PCSK9 levels, especially among statin users 7) . Additionally, in an intervention study, alteration of saturated fat intake with unsaturated fat intake, which will lower CHD risk, improved LDL cholesterol levels but not serum PCSK9 levels 8) . These findings suggest that serum PCSK9 level could not be modified by improving physical activity and dietary intake although CHD risk could be modified. To interpret the meaning of high serum PCSK9 level on CHD risk in the general population, further investigation is warranted. Additionally, the assessment of the CHD risk prediction performance and the cost–benefit balance by adding serum PCSK9 level to the Suita score 9) , which is adopted in the Japan Atherosclerosis Society Guideline for Prevention of Atherosclerotic Cardiovascular Diseases 2017 10) , has been waited for to determine whether serum PCSK9 level is useful for CHD risk assessment.
The author has no conflict of interest in this paper.
