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. 2020 Sep;22(9):1607-1618.
doi: 10.1111/dom.14074. Epub 2020 Jun 3.

Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study

Kåre I Birkeland  1 , Johan Bodegard  2 , Jan W Eriksson  3 , Anna Norhammar  4 , Hermann Haller  5 , Gerard C M Linssen  6 , Amitava Banerjee  7   8 , Marcus Thuresson  9 , Suguru Okami  10 , Elena Garal-Pantaler  11 , Jetty Overbeek  12 , Jil Billy Mamza  13 , Ruiqi Zhang  13 , Toshitaka Yajima  10 , Issei Komuro  14 , Takashi Kadowaki  15   16
Affiliations

Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study

Kåre I Birkeland et al. Diabetes Obes Metab. 2020 Sep.

Abstract

Aims: To examine the manifestation of cardiovascular or renal disease (CVRD) in patients with type 2 diabetes (T2D) initially free from CVRD as well as the mortality risks associated with these diseases.

Methods: Patients free from CVRD were identified from healthcare records in England, Germany, Japan, the Netherlands, Norway and Sweden at a fixed date. CVRD manifestation was defined by first diagnosis of cardiorenal disease, or a stroke, myocardial infarction (MI) or peripheral artery disease (PAD) event. The mortality risk associated with single CVRD history of heart failure (HF), chronic kidney disease (CKD), MI, stroke or PAD was compared with that associated with CVRD-free status.

Results: Of 1 177 896 patients with T2D, 772 336 (66%) were CVRD-free and followed for a mean of 4.5 years. A total of 137 081 patients (18%) developed a first CVRD manifestation, represented by CKD (36%), HF (24%), stroke (16%), MI (14%) and PAD (10%). HF or CKD was associated with increased cardiovascular and all-cause mortality risk: hazard ratio (HR) 2.02 (95% confidence interval [CI] 1.75-2.33) and HR 2.05 (95% CI 1.82-2.32), respectively. HF and CKD were separately associated with significantly increased mortality risks, and the combination was associated with the highest cardiovascular and all-cause mortality risk: HRs 3.91 (95% CI 3.02-5.07) and 3.14 (95% CI 2.90-3.40), respectively.

Conclusion: In a large multinational study of >750 000 CVRD-free patients with T2D, HF and CKD were consistently the most frequent first cardiovascular disease manifestations and were also associated with increased mortality risks. These novel findings show these cardiorenal diseases to be important and serious complications requiring improved preventive strategies.

Keywords: SGLT2 inhibitor; diabetic nephropathy; heart failure; macrovascular disease; observational study; type 2 diabetes.

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Conflict of interest statement

K.I.B. has received grants to his institution from AstraZeneca for this study and for lectures and consulting from Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim and Merck Sharp & Dohme. J.B. holds a full‐time position at AstraZeneca as an epidemiologist. J.W.E. has received honoraria or research grants from AstraZeneca, NovoNordisk, Bayer, Sanofi and MSD. A.N. has received honoraria from MSD, Astra Zeneca, Eli Lilly, Boehringer Ingelheim and Novo Nordisk. H.H has received lecture fees and travel expenses from Alexion, Baxter, NovoNordisk, Noxxon, Janssen and AstraZeneca. G.C.M.L. has no competing interests. M.T. is employed by an independent statistical consultant company, Statisticon AB, Uppsala, Sweden, of which AstraZeneca Nordic‐Baltic is a client. S.O. is a full‐time employee of AstraZeneca. E.G.P. is an employee of Team Gesundheit GmbH and conducted work on behalf of Kantar Health. J.O. is an employee of the PHARMO Institute for Drug Outcomes Research, an independent research institute that performs financially supported studies for government and related healthcare authorities and for several pharmaceutical companies. R.Z. and T.Y. are full‐time employees of AstraZeneca. I.K. declares grants from Astellas Pharma Inc., Boehringer Ingelheim Japan, Kowa Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Mitsubishi Tanabe Pharma Corp., Shionogi & Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd, Toa Eiyo Ltd, honoraria from Astellas Pharma Inc., Boehringer Ingelheim Japan, Kowa Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd, Mitsubishi Tanabe Pharma Corp., Shionogi & Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd, Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd and Toa Eiyo Ltd, and lecture/other fees from AstraZeneca. T.K. declares grants from Asahi Mutual Life Insurance Co., Boehringer Ingelheim Japan, Daiichi Sankyo Co. Ltd, Kowa Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma Corp., MSD K.K., Novo Nordisk Pharma Ltd, Sanofi K.K. and Takeda Pharmaceutical Co. Ltd and lecture/other fees from AstraZeneca K.K., Astellas Pharma Inc., Boehringer Ingelheim Japan, Daiichi Sankyo Co. Ltd, Eli Lilly Japan K.K., Kowa Pharmaceutical Co. Ltd, Kyowa Hakko Kirin Co., Ltd, Mitsubishi Tanabe Pharma Corp., MSD K.K., Ono Pharmaceutical Co. Ltd, Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd, Sanwa Kagaku Kenkyusho Co. Ltd, Taisho Pharmaceutical Co., Ltd and Takeda Pharmaceutical Co, Ltd.

Figures

FIGURE 1
FIGURE 1
Cardiovascular manifestation during follow‐up in initially cardiovascular or renal disease‐free patients with type 2 diabetes. CKD, chronic kidney disease; HF, heart failure
FIGURE 2
FIGURE 2
Pooled death risks associated with the single presence groups of cardiovascular or renal disease (CVRD) compared to a CVRD‐free type 2 diabetes group. Cardiorenal disease defined as heart failure (HF) or chronic kidney disease (CKD). Cardiorenal syndrome defines as the presence of both HF and CKD). *Adjusted for age and sex. **Cardiovascular disease (CVD) death was not obtainable in Germany, Japan and the Netherlands
FIGURE 3
FIGURE 3
Pooled cardiovascular risks associated with the single presence groups of cardiovascular or renal disease (CVRD) compared to a CVRD‐free type 2 diabetes group. Cardiorenal disease defined as heart failure (HF) or chronic kidney disease (CKD). Cardiorenal syndrome defines as the presence of both HF and CKD). *Adjusted for age and sex
See this image and copyright information in PMC

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