Takehiro Funamizu1, Hiroshi Iwata2, Yuya Nishida3, Katsutoshi Miyosawa1,4, Shinichiro Doi1, Yuichi Chikata1, Jun Shitara5, Hirohisa Endo1, Hideki Wada5, Ryo Naito6, Manabu Ogita5, Tomotaka Dohi1, Takatoshi Kasai1, Shinya Okazaki1, Kikuo Isoda1, Katsumi Miyauchi1, Hiroyuki Daida1. 1. Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan. 2. Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan. hiroiwata-circ@umin.ac.jp. 3. Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. 4. Tokyo New Drug Research Laboratories, Kowa Company, Ltd., Tokyo, Japan. 5. Department of Cardiovascular Medicine, Juntendo University, Shizuoka Hospital, Shizuoka, Japan. 6. Department of Cardiovascular Medicine, Juntendo University Urayasu Hospital, Chiba, Japan.
Abstract
BACKGROUND: In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI). METHODS: This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5-7.0% (n = 268), 7.0-7.5% (n = 262), 7.5-8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years. RESULTS: In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan-Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0-7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0-7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0-7.5%: 2.97, 95% confidence interval: 1.33-7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0-7.5% group. CONCLUSION: The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes. Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).
BACKGROUND: In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabeticpatients undergoing percutaneous coronary intervention (PCI). METHODS: This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5-7.0% (n = 268), 7.0-7.5% (n = 262), 7.5-8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years. RESULTS: In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan-Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0-7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0-7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0-7.5%: 2.97, 95% confidence interval: 1.33-7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0-7.5% group. CONCLUSION: The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes. Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).
Authors: Christoph Sinning; Nataliya Makarova; Stefan Söderberg; Marco M Ferrario; Barbara Thorand; Henry Völzke; Renate B Schnabel; Francisco Ojeda; Marcus Dörr; Stephan B Felix; Wolfgang Koenig; Annette Peters; Wolfgang Rathmann; Ben Schöttker; Hermann Brenner; Giovanni Veronesi; Giancarlo Cesana; Paolo Brambilla; Tarja Palosaari; Kari Kuulasmaa; Inger Njølstad; Ellisiv Bøgeberg Mathiesen; Tom Wilsgaard; Stefan Blankenberg Journal: Cardiovasc Diabetol Date: 2021-11-15 Impact factor: 9.951