We read with great interest the article by Liu et al 1 Liu C Dhindsa D Almuwaqqat Z Sun YV Quyyumi AA. Very high high-density lipoprotein cholesterol levels and cardiovascular mortality. Am J Cardiol. 2022; 167: 43-53 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar reporting that very high high-density lipoprotein cholesterol (HDL-C) levels (>80 mg/100 ml) are associated with an increased risk of all-cause death among men but not among women from 415,416 participants free of coronary artery disease in the United Kingdom Biobank. This conclusion reminds us of the findings of Takaeko et al 2 Takaeko Y Matsui S Kajikawa M Maruhashi T Kishimoto S Hashimoto H Kihara Y Hida E Chayama K Goto C Aibara Y Yusoff FM Noma K Nakashima A Higashi Y. Association of extremely high levels of high-density lipoprotein cholesterol with endothelial dysfunction in men. J Clin Lipidol. 2019; 13 (664–672.e1) Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar ,3 Takaeko Y Matsui S Kajikawa M Maruhashi T Yamaji T Harada T Han Y Hashimoto H Kihara Y Hida E Chayama K Goto C Aibara Y Yusoff FM Kishimoto S Nakashima A Higashi Y. Relationship between high-density lipoprotein cholesterol levels and endothelial function in women: a cross-sectional study. BMJ Open. 2020; 10e038121 Crossref PubMed Scopus (6) Google Scholar that extremely high HDL-C levels (≥80 mg/100 ml) were associated with a significant reduction in flow-mediated vasodilation in men but not in women. Regarding the current article by Liu et al, 1 Liu C Dhindsa D Almuwaqqat Z Sun YV Quyyumi AA. Very high high-density lipoprotein cholesterol levels and cardiovascular mortality. Am J Cardiol. 2022; 167: 43-53 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar 2 issues should be emphasized.