Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese
The ability of pro-protein convertase subtilisin/kexin type 9 (PCSK9) levels to predict the presence or severity of coronary artery disease (CAD) remains controversial. The purpose of this study was to investigate these associations. We enrolled 393 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and underwent multidetector-row computed tomography coronary angiography. The presence of CAD (≥50% coronary stenosis), the number of significantly stenosed coronary vessels, and plasma levels of PCSK9 by ELISA were analyzed. Plasma PCSK9 levels (log-transformed data) were significantly associated with the presence of CAD. Next, we divided the patients into two groups (non-statin and statin groups) according to statin treatment. PCSK9 levels in the non-statin group were significantly lower than those in the statin group. There were no significant differences in PCSK9 levels between the absence and presence of CAD in the statin group. However, in the non-statin group, PCSK9 levels in patients with CAD were significantly higher than those in patients without CAD. PCSK9 levels, in addition to age, gender, BMI, DM and HDL-C, were independently associated with the presence of CAD by a multivariable analysis. In conclusion, our results demonstrated that plasma PCSK9 levels may be a marker for evaluating the presence of CAD.
KeywordsPro-protein convertase subtilisin/kexin type 9 Coronary artery disease Multidetector-row computed tomography Statin
Compliance with ethical standards
Conflict of interest
KS and SM are Directors of NPO Clinical and Applied Science, Fukuoka, Japan. KS and SM received a grant from the Public Interest Incorporated Foundation of “Clinical Research Promotion Foundation” in Fukuoka, Japan, and part of this work was transferred to NPO Clinical and Applied Science, Fukuoka, Japan. KS has an Endowed Department of Molecular Cardiovascular Therapeutics (SM), Fukuoka University, supported by MSD Co., Ltd.
- 2.Sun H, Samarghandi A, Zhang N, Yao Z, Xiong M, Teng BB (2012) Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor. Arterioscler Thromb Vasc Biol 32:1585–1595CrossRefGoogle Scholar
- 12.Li JJ, Li S, Zhang Y, Xu RX, Guo YL, Zhu CG, Wu NQ, Qing P, Gao Y, Sun J, Liu G, Dong Q (2015) Proprotein convertase subtilisin/kexin type 9, C-reactive protein, coronary severity, and outcomes in patients with stable coronary artery disease: a prospective observational cohort study. Med (Baltim) 94:e2426CrossRefGoogle Scholar
- 15.Leander K, Malarstig A, Van’t Hooft FM, Hyde C, Hellenius ML, Troutt JS, Konrad RJ, Ohrvik J, Hamsten A, de Faire U (2016) Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) predicts future risk of cardiovascular events independently of established risk factors. Circulation 133:1230–1239CrossRefGoogle Scholar
- 17.Gijsberts CM, den Ruijter HM, Asselbergs FW, Chan MY, de Kleijn DP, Hoefer IE (2015) Biomarkers of coronary artery disease differ between Asians and Caucasians in the general population. Glob Heart 10(301–311):e11Google Scholar
- 18.Verschuren WM, Jacobs DR, Bloemberg BP, Kromhout D, Menotti A, Aravanis C, Blackburn H, Buzina R, Dontas AS, Fidanza F, Karvonen MJ, Nedelijkovic SM, Nissinen A, Toshima H (1995) Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study. JAMA 274:131–136CrossRefGoogle Scholar
- 19.Mitsutake R, Niimura H, Miura S, Zhang B, Iwata A, Nishikawa H, Kawamura A, Kumagai K, Shirai K, Matsunaga A, Saku K (2006) Clinical significance of the coronary calcification score by multidetector row computed tomography for the evaluation of coronary stenosis in Japanese patients. Circ J 70:1122–1127CrossRefGoogle Scholar
- 21.Sinning C, Lillpopp L, Appelbaum S, Ojeda F, Zeller T, Schnabel R, Lubos E, Jagodzinski A, Keller T, Munzel T, Bickel C, Blankenberg S (2013) Angiographic score assessment improves cardiovascular risk prediction: the clinical value of SYNTAX and Gensini application. Clin Res Cardiol 102:495–503CrossRefGoogle Scholar
- 24.Wang S, Cheng ZY, Zhao ZN, Quan XQ, Wei Y, Xia DS, Li JQ, Hu JL (2016) Correlation of serum PCSK9 in CHD patients with the severity of coronary arterial lesions. Eur Rev Med Pharmacol Sci 20:1135–1139Google Scholar