Heart Failure and Chronic Kidney Disease Manifestation and Mortality Risk -Associations in Type 2 Diabetes: A Large Multinational Cohort Study

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 137081 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 allcause 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.