Abstract
It is unclear whether higher levels of serum high-density lipoprotein cholesterol (HDL-C) prevent major adverse cardiovascular events (MACE). We prospectively evaluated 501 patients who had undergone coronary computed tomography angiography at Fukuoka University Hospital and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The primary endpoint was MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into tertiles according to the HDL-C level: 47 mg/dl ≥ HDL-C level [n = 167, lower HDL-C level (L-HDL)], 58 mg/dl ≥ HDL-C level ≥ 48 mg/dl [n = 167, middle HDL-C level (M-HDL)] and HDL-C level ≥ 59 mg/dl [n = 167, higher HDL-C level (H-HDL)] groups. There were significant differences in %CAD among the L-HDL, M-HDL and H-HDL groups. Unexpectedly, there was no difference in %MACE between M-HDL and H-HDL, although %MACE in M-HDL was significantly lower than that in L-HDL (p < 0.05). By a multivariate logistic regression analysis, MACE in H-HDL-C was independently associated with diabetes mellitus (DM) (p = 0.03). A Kaplan–Meier curve according to the HDL subgroup indicated that M-HDL, not H-HDL, enjoyed the greatest freedom from MACE among the 3 groups (log-rank test p = 0.047). Finally, the results of a Cox regression model indicated that L-HDL and H-HDL had significantly higher risk of MACE than M-HDL. In conclusions, patients with middle HDL-C levels, not higher HDL-C levels, showed the greatest freedom from MACE. Patients with higher HDL-C levels need to be strictly managed for DM to prevent MACE.
Similar content being viewed by others
References
Chapman MJ, Redfern JS, McGovern ME, Giral P (2010) Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Therapeutics 126:314–345
Mora S, Wenger NK, Demicco DA, Breazna A, Boekholdt SM, Arsenault BJ, Deedwania P, Kastelein JJ, Waters DD (2012) Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the treating to new targets (TNT) study. Circulation 125:1979–1987
Miura S, Shiga Y, Ike A, Iwata A (2019) Atherosclerotic coronary artery disease in patients with cardiometabolic syndrome. Cardiol Res 10:69–73
M Kinoshita K Yokote H Arai M Iida Y Ishigaki S Ishibashi S Umemoto G Egusa H Ohmura T Okamura S Kihara S Koba I Saito T Shoji H Daida K Tsukamoto J Deguchi S Dohi K Dobashi H Hamaguchi M Hara T Hiro S Biro Y Fujioka C Maruyama Y Miyamoto Y Murakami M Yokode H Yoshida H Rakugi A Wakatsuki S Yamashita Committee for Epidemiology and Clinical Management of Atherosclerosis (2018) Japan atherosclerosis society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017. J Atheroscler Thromb 25:846–984
Di Bartolo BA, Psaltis PJ, Bursill CA, Nicholls SJ (2018) Translating evidence of HDL and plaque regression. Arterioscler Thromb Vasc Biol 38:1961–1968
Armitage J, Holmes MV, Preiss D (2019) Cholesteryl ester transfer protein inhibition for preventing cardiovascular events: JACC review topic of the week. J Am Coll Cardiol 73:477–487
Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW (2014) HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 371:2383–2393
Imaizumi S, Miura S, Takata K, Takamiya Y, Kuwano T, Sugihara M, Ike A, Iwata A, Nishikawa H, Saku K (2015) Association between cholesterol efflux capacity and coronary restenosis after successful stent implantation. Heart Vessels 31:1257–1265
Annema W, Dikkers A, Freark de Boer J, Dullaart RPF, Sanders JSF, Bakker SJL, Tietge UJF (2016) HDL cholesterol efflux predicts graft failure in renal transplant recipients. J Am Soc Nephrol 27:595–603
Hirata A, Sugiyama D, Watanabe M, Tamakoshi A, Iso H, Kotani K, Kiyama M, Yamada M, Ishikawa S, Murakami Y, Miura K, Ueshima H, Okamura T, Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH–JAPAN) Research Group (2018) Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: the EPOCH-JAPAN study. J Clin Lipidol 12:674–684
Reimann AJ, Tsiflikas I, Pecha S, Blumenstock G, Teufel M, Drosch T, Heuschmid M, Schröder S, Claussen CD, Burgstahler C (2011) Prognostic value of significant and non-significant coronary artery stenosis detection using MDCT for major adverse cardiac events. Int J Cardiol 149:126–128
Cho I, Chang HJ, Sung JM, Pencina MJ, Lin FY, Dunning AM, Achenbach S, Al-Mallah M, Berman DS, Budoff MJ, Callister TQ, Chow BJW, Delago A, Hadamitzky M, Hausleiter J, Maffei E, Cademartiri F, Kaufmann P, Shaw LJ, Raff GL, Chinnaiyan KM, Villines TC, Cheng V, Nasir K, Gomez M, Min LK, Investigators CONFIRM (2012) Coronary computed tomographic angiography and risk of all-cause mortality and nonfatal myocardial infarction in subjects without chest pain syndrome from the confirm registry (coronary CT angiography evaluation for clinical outcomes: an international multicenter registry). Circulation 126:304–313
Muhlestein JB, Lappe DL, Lima JA, Rosen BD, May HT, Knight S, Bluemke DA, Towner SR, Le V, Bair TL, Vavere AL, Anderson JL (2014) Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the factor-64 randomized clinical trial. JAMA 312:2234–2243
Kang SH, Park GM, Lee SW, Yun SC, Kim YH, Cho YR, Park HW, Suh J, Yang DH, Kang JW, Lim TH, Jung CH, Koh EH, Lee WJ, Kim MS, Lee KU, Park JY (2016) Long-term prognostic value of coronary CT angiography in asymptomatic type 2 diabetes mellitus. JACC Cardiovasc Imaging 9:1292–1300
Gnanenthiran SR, Naoum C, Leipsic JA, Achenbach S, Al-Mallah MH, Andreini D, Bax JJ, Berman DS, Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Chinnaiyan K, Chow BJW, Cury RC, DeLago A, Feuchtner G, Hadamitzky M, Hausleiter J, Kaufman PA, Kim YJ, Maffei E, Marques H, de Araújo GP, Pontone G, Raff GL, Rubinshtein R, Shaw LJ, Villines TC, Gransar H, Lu Y, Jones EC, Peña JM, Lin FY, Kritharides L, Min JK (2019) Long-term prognostic utility of computed tomography coronary angiography in older populations. Eur Heart J Cardiovasc Imaging 20:1279–1286
Moon SJ, Chun EJ, Yoon YE, Park KS, Jang HC, Lim S (2019) Long-term prognostic value of coronary computed tomography angiography in an asymptomatic elderly population. J Am Heart Assoc 8:e013523
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 70:1122–1127
Mitsutake R, Miura S, Kawamura A, Saku K (2009) Are metabolic factors associated with coronary artery stenosis by MDCT? Circ J 73:132–138
Mitsutake R, Miura S, Zhang B, Saku K (2010) HDL-associated factors provide additional prognostic information for coronary disease as determined by multi-detector row computed tomography. Int J Cardiol 143:72–78
Shiga Y, Miura S, Mitsutake R, Kawamura A, Uehara Y, Saku K (2010) Significance of serum high-density lipoprotein cholesterol levels for diagnosis of coronary stenosis as determined by MDCT in patients with suspected coronary artery disease. J Atheroscler Thromb 17:870–878
Shiga Y, Miura S, Mitsutake R, Yamagishi S, Saku K (2011) Significance of plasma levels of pigment epithelium-derived factor in patients with mild chronic kidney disease and/or coronary artery disease as determined by multi-detector row computed tomography. J Int Med Res 39:880–890
Nakamura A, Miura S, Shiga Y, Norimatsu K, Miyase Y, Suematsu Y, Mitsutake R, Saku K (2015) Is Pentraxin 3 a biomarker, a player, or both in the context of coronary atherosclerosis and metabolic factors? Heart Vessels 30:752–761
Norimatsu K, Miura S, Suematsu Y, Shiga Y, Miyase Y, Nakamura A, Yamada M, Matsunaga A, Saku K (2015) Associations between glycated albumin or hemoglobinA1c and the presence of coronary artery disease. J Cardiol 65:487–493
Yano M, Miura S, Shiga Y, Miyase Y, Suematsu Y, Norimatsu N, Nakamura A, Adachi S, Nishikawa H, Keijiro Saku K (2016) Association between smoking habits and severity of coronary stenosis as assessed by coronary computed tomography angiography. Heart Vessels 31:1061–1068
Norimatsu K, Kuwano T, Miura S, Shimizu T, Shiga Y, Suematsu Y, Miyase Y, Adachi S, Nakamura A, Imaizumi S, Iwata A, Nishikawa H, Uehara Y, Saku K (2017) Significance of the percentage of cholesterol efflux capacity and total cholesterol efflux capacity in patients with or without coronary artery disease. Heart Vessels 32:30–38
Ueda Y, Shiga Y, Idemoto Y, Tashiro K, Motozato K, Koyoshi R, Kuwano T, Fujimi K, Ogawa M, Keijiro Saku K, Miura S (2018) Association between the presence or severity of coronary artery disease and pericardial fat, paracardial fat, epicardial fat, visceral fat and subcutaneous fat as assessed by multi-detector row computed tomography. Int Heart J 59:695–704
Nose D, Shiga Y, Ueda Y, Idemoto Y, Tashiro K, Suematsu Y, Kuwano T, Kitajima K, Saku K, Miura S (2019) Relationship between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese. Heart Vessels 34:19–28
Gensini GG (1983) A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 51:606
Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832
Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, Horio T, Hoshide S, Ikeda S, Ishimitsu T, Ito M, Ito S, Iwashima Y, Kai H, Kamide K, Kanno Y, Kashihara N, Kawano Y, Kikuchi T, Kitamura K, Kitazono T, Kohara K, Kudo M, Kumagai H, Matsumura K, Matsuura H, Miura K, Mukoyama M, Nakamura S, Ohkubo T, Ohya Y, Okura T, Rakugi H, Saitoh S, Shibata H, Shimosawa T, Suzuki H, Takahashi S, Tamura K, Tomiyama H, Tsuchihashi T, Ueda S, Uehara Y, Urata H, Hirawa N (2019) The Japanese society of hypertension guidelines for the manageme nt of hypertension (JSH 2019). Hypertens Res 42:1235–1481
American Diabetes Association (2004) Screening for type 2 diabetes. Diabetes Care 27:S11–S14
Farbstein D, Levy AP (2012) HDL dysfunction in diabetes: causes and possible treatments. Expert Rev Cardiovasc Ther 10:353–361
Sviridov D, Mukhamedova N, Remaley AT, Chin-Dusting J, Nestel P (2008) Antiatherogenic functionality of high density lipoprotein: how much versus how good. J Atheroscler Thromb 15:52–62
Ropers D, Rixe J, Anders K, Küttner A, Baum U, Bautz W, Daniel WG, Achenbach S (2006) Usefulness of multidetector row computed tomography with 64- × 0.6 mm collimation and 330 ms rotation for the noninvasive detection of significant coronary artery stenoses. Am J Cardiol 97:343–348
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kawahira, Y., Shiga, Y., Inoue, H. et al. Association between high-density lipoprotein cholesterol levels and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography: FU-CCTA registry. Heart Vessels 36, 1457–1465 (2021). https://doi.org/10.1007/s00380-021-01831-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-021-01831-0