HF and CKD most frequent first CV- and renal disease manifestations in T2DM

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

Literature - Birkeland KI, Bodegard J, Eriksson JW et al., - Diabetes Obes Metab. 2020. doi: 10.1111/dom.14074.

Introduction and methods

HF and CKD, also known as cardiorenal disease, have a high prevalence and CV and mortality risk among patients with T2DM [1-11]. The seriousness of both conditions is further accentuated because HF can lead to kidney failure and vice versa, resulting in cardiorenal syndrome (CRS) [12, 13]. It has been demonstrated that risks of HF and CKD remain high in patients with T2D despite the use of established treatment strategies for CVD [14-16]. In addition, it is not well understood how HF and CKD temporally develop in patients with T2DM.

The present multinational cohort study evaluated the temporal development of HF and CKD among T2D-patients (n=772,336) in England, Germany, Japan, the Netherlands, Norway and Sweden, who were initially free of cardiovascular- and renal disease (CVRD). CVRD-free T2DM patients were defined as those patients without any recorded history of CV or renal disease, including stroke, MI, (unstable) angina pectoris, AF, HF, coronary revascularization, PAD, peripheral artery revascularization or CKD. They were examined from index to the first recorded CVRD event. First CVRD event was defined by first recorded out- or in-hospital diagnosis of HF, CKD, cardiorenal disease (HF or CKD), stroke, MI or PAD. In addition, for comparison with CVRD-free patients, patients with a single CVRD manifestation were also identified at index, including manifestations of stroke, MI, PAD, HF or CKD, and its separate components HF, CKD and CRS. Outcomes to estimate risk associations included all-cause death, CVD death, and mentioned CVRD outcomes. Mean follow-up was 4.5 years.

Main results

  • Of 772,336 CVRD-free T2DM patients, 18% developed a first CVRD manifestation during follow-up. The proportion of patients who experienced cardiorenal disease increased early during follow-up, compared to the proportion of patients who experienced stroke, MI or PAD. Cardiorenal disease (HF or CKD) was the most frequent first CVRD manifestation across countries (cardiorenal disease 60%, consisting of HF 24% and CKD 36%; stroke 16%, MI 14% and PAD 10%).
  • Compared to CVRD-free T2DM patients, patients with a single manifestation of cardiorenal disease had increased all-cause mortality risk (HR 2.02, 95%CI: 1.75-2.33) and increased CVD mortality risk (HR 2.05, 95%CI: 1.82-2.32).
  • Similarly, single manifestations of separate components of cardiorenal disease, HF, CKD and CRS, were also associated with increased risk of all-cause mortality (HF: HR 2.30, 95%CI: 2.14-2.47; CKD: HR 1.88, 95%CI: 1.59-2.22; CRS: HR 3.14, 95%CI: 2.90-3.40) and CVD mortality (HF: HR 2.76, 95%CI: 2.12-3.59; CKD: HR 1.79, 95%CI: 1.59-2.02; CRS: HR 3.91, 95%CI: 3.02-5.07), compared to the CVRD-free group.
  • Single manifestations of cardiorenal disease and its separate components were also associated with increased risk of CVD events, including MI (cardiorenal disease: HR 1.55, 95%CI 1.45-1.65; HF: HR 1.45, 95%CI: 1.21-1.75; CKD: HR 1.59, 95%CI: 1.52-1.67; CRS: HR 2.16, 95%CI: 1.51-3.09), stroke (cardiorenal disease: HR 1.35, 95%CI 1.28-1.43, HF: HR 1.43, 95%CI: 1.29-1.59; CKD: HR 1.33, 95%CI: 1.22-1.45; CRS: HR 1.73, 95%CI: 1.45-2.06) and PAD (cardiorenal disease: HR 1.96, 95%CI 1.69-2.27, HF: HR 1.66, 95%CI: 1.40-1.97; CKD: HR 2.14, 95%CI: 1.74-2.62; CRS: HR 3.16, 95%CI: 2.31-4.34), compared to the CVRD free group.
  • Compared to CVRD-free T2DM patients, single manifestation of HF was associated with increased risk of incident CKD (HR 2.30, 95%CI: 2.00-2.65) and single manifestation of CKD was associated with increased risk of HF (HR 1.99, 95% CI: 1.75-2.26).


Among T2DM patients initially free from CVRD, cardiorenal disease (HF or CKD) was the most frequent first CVRD manifestation. Patients with single presence of cardiorenal disease had an increased all-cause and CVD mortality risk, as well as an increased risk of MI, stroke and PAD, compared to patients with no history of CVRD.


1. Birkeland KI, Bodegard J, Norhammar A, Kuiper JG, Georgiado E, Beekman-Hendriks WL, et al. How

representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study. Diabetes Obes Metab. 2018;24:968-74.

2. Thrainsdottir IS, Aspelund T, Thorgeirsson G, Gudnason V, Hardarson T, Malmberg K, et al. The association between glucose abnormalities and heart failure in the population-based Reykjavik study. Diabetes Care. 2005;28(3):612-6.

3. Collaboration GBDCKD. Global, regional, and national burden of chronic kidney disease, 1990-2017: a

systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-33.

4. Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC, Jr. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004;27(3):699-703.

5. Bruck K, Stel VS, Gambaro G, Hallan S, Volzke H, Arnlov J, et al. CKD Prevalence Varies across the European General Population. J Am Soc Nephrol. 2016;27(7):2135-47.

6. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382(9889):339-52.

7. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death,

cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296-305.

8. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-89.

9. Kerr M, Bray B, Medcalf J, O'Donoghue DJ, Matthews B. Estimating the financial cost of chronic kidney disease to the NHS in England. Nephrol Dial Transplant. 2012;27 Suppl 3:iii73-80.

10. Seuring T, Archangelidi O, Suhrcke M. The Economic Costs of Type 2 Diabetes: A Global Systematic Review. Pharmacoeconomics. 2015;33(8):811-31.

11. van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int. 2011;79(12):1341-52.

12. Ismail Y, Kasmikha Z, Green HL, McCullough PA. Cardio-renal syndrome type 1: epidemiology,

pathophysiology, and treatment. Semin Nephrol. 2012;32(1):18-25.

13. Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, et al. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation. 2019;139(16):e840-e78.

14. Rawshani A, Rawshani A, Franzen S, Sattar N, Eliasson B, Svensson AM, et al. Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2018;379(7):633-44.

15. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-8.

16. de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA. 2011;305(24):2532-9.

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