HF development after T2DM diagnosis associated with highest 5-year risk of death

Type 2 Diabetes Mellitus and Impact of Heart Failure on Prognosis Compared to Other Cardiovascular Diseases: A Nationwide Study

Literature - Zareini B, Blanche P, D'Souza M et al., - Circ Cardiovasc Qual Outcomes. 2020. doi: 10.1161/CIRCOUTCOMES.119.006260.

Introduction and methods

Observational studies in patients with T2DM have reported increased rates of mortality following myocardial infarction, stroke, chronic kidney disease (CKD) and heart failure (HF) [1-11]. However, the risk profile among real-life patients with newly diagnosed T2DM who develop CV and renal disease remains unknown [12,13]. Moreover, the prognostic importance in terms of mortality risk of CV and renal diagnoses in T2DM patients is still uncertain. This nationwide study estimated the absolute 5-year risk of death, the 5-year risk ratio (RR) of death and decrease in lifespan in patients with newly diagnosed T2DM who developed HF, ischemic heart disease (IHD), stroke, CKD, or peripheral artery disease (PAD) after diagnosis of T2DM.

Data were collected from 4 nationwide Danish registers: The Danish National Patient Registry, The Danish National Prescription Registry, The Danish Cause of Death Registry and The Danish Civil registry. A total of 153,405 patients with newly diagnosed T2DM between 1998 and 2015 and with no prior CV or renal diagnoses were included.

The primary outcome was all-cause death. Patients were followed until the end of the study period (December 31, 2015), death or emigration. Median follow-up was 9.7 years (IQR 5.8-13.9 years).

Main results

Patients who developed HF had the highest 5-year risk of death among patients alive 5 years after T2DM diagnosis (47.6%, 95%CI 44.8-50.3), compared with T2DM patients who developed IHD (21.0%, 95%CI 20-22), stroke (34.5%, 95%CI 32.6-36.4), CKD (27.7%, 95%CI 25.5-30.0), and PAD (37.1%, 95%CI 34.6-39.5).
Compared to T2DM patients without CV and renal disease, patients who developed HF within 5 years after diagnosis of T2DM had a 3 times higher 5-year RR of death (95%CI 2.9-3.1). The corresponding 5-year RR of death were lower for patients who developed IHD (RR 1.3, 95%CI 1.3-1.4), stroke (RR 2.2, 95%CI 2.1-2.2), CKD (RR 1.7, 95%CI 1.7-1.8), and PAD (RR 2.3, 95%CI 2.3-2.4).
Patients who developed HF within 5 years following onset of T2DM had an average decrease in lifespan of 11.7 months, compared with T2DM patients free of CV and renal disease (95%CI 11.6-11.8). Smaller decreases in lifespan were found for other diagnoses: IHD (1.6 months, 95%CI 1.5-1.7), stroke (6.4 months, 95%CI 6.3-6.5), CKD (4.4 months, 95%CI 4.3-4.6), PAD (6.9 months, 95%CI 6.8-7.0).
When looking at the prognosis after developing a combination of 2 CV or renal diseases, the highest 5-year risks of death were found in patients who developed HF in combination with stroke (54.1%, 95%CI 44.7-63.5) or CKD (63.7%, 95%CI 53.7-73.7). The 5-year risk of death in patients who developed HF in combination with PAD was 48.4% (95%CI 36.4-60.5) and 45.5% in patients who developed HF and IHD (95%CI 42.3-48.7). The 5-year risks of death in patients who developed IDH in combination with stroke, CKD, or PAD were 39.9% (95%CI 34.8-45), 38.4% (95%CI 32.7-44.1), and 39.5% (95%CI 34.4-44.5), respectively.
The 5-year RR of death was highest among T2DM patients with HF in combination with stroke (RR 3.4, 95%CI 3.3-3.5), CKD (RR 4.0, 95%CI 3.9-4.1), or PAD (RR 3.1, 95%CI 3.0-3.1). Other combinations of CV or renal diseases did not exceed a RR estimate above 3.0.
The lifespan in patients who developed HF within 5 years following onset of T2DM in combination with stroke, CKD, PAD, or IHD decreased by 16.2 months (95%CI 16.1-16.4), 18.2 months (95%CI 18.1-18.3), 14.3 months (95%CI 14.2-14.4), and 11 months (10.9-11.2), respectively. The lifespan in patients developing IHD in combination with stroke, CKD, or PAD decreased by 7.9 months (95%CI 7.8-8.0), 7.9 months (95%CI 7.8-8.1), or 8.6 months (95%CI 8.5-8.7), respectively.

Conclusion

Among patients with newly diagnosed T2DM, those who developed HF alone or in combination with stroke, CKD or PAD had the highest 5-year absolute and relative risk of death and the greatest decrease in lifespan when compared with development of other (combinations of) CV and renal diseases.

References

Show references

1. Chun BY, Dobson AJ, Heller RF. The impact of diabetes on survival among patients with first myocardial infarction. Diabetes Care. 1997;20:704–708. doi: 10.2337/diacare.20.5.704

2. Norgaard ML, Andersen SS, Schramm TK, Folke F, Jørgensen CH, Hansen ML, Andersson C, Bretler DM, Vaag A, Køber L, Torp-Pedersen C, Gislason GH. Changes in short- and long-term cardiovascular risk of incident diabetes and incident myocardial infarction–a nationwide study. Diabetologia. 2010;53:1612–1619. doi: 10.1007/s00125-010-1783-z

3. Koek HL, Soedamah-Muthu SS, Kardaun JW, Gevers E, de Bruin A, Reitsma JB, Bots ML, Grobbee DE. Short- and long-term mortality after acute myocardial infarction: comparison of patients with and without diabetes mellitus. Eur J Epidemiol. 2007;22:883–888. doi: 10.1007/s10654-007-9191-5

4. Jhund PS, McMurray JJ, Chaturvedi N, Brunel P, Desai AS, Finn PV, Haffner SM, Solomon SD, Weinrauch LA, Claggett BL, Pfeffer MA. Mortality following a cardiovascular or renal event in patients with type 2 diabetes in the ALTITUDE trial. Eur Heart J. 2015;36:2463–2469. doi: 10.1093/eurheartj/ehv295

5. Icks A, Claessen H, Morbach S, Glaeske G, Hoffmann F. Time-dependent impact of diabetes on mortality in patients with stroke: survival up to 5 years in a health insurance population cohort in Germany. Diabetes Care. 2012;35:1868–1875. doi: 10.2337/dc11-2159

6. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR; UKPDS GROUP. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63:225–232. doi: 10.1046/j.1523-1755.2003.00712.x

7. Andrésdóttir G, Jensen ML, Carstensen B, Parving HH, Rossing K, Hansen TW, Rossing P. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors. Diabetes Care. 2014;37:1660–1667. doi: 10.2337/dc13-2036

8. MacDonald MR, Jhund PS, Petrie MC, Lewsey JD, Hawkins NM, Bhagra S, Munoz N, Varyani F, Redpath A, Chalmers J, MacIntyre K, McMurray JJ. Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland. Circ Heart Fail. 2008;1:234–241. doi:10.1161/CIRCHEARTFAILURE.108.794008

9. Kristensen SL, Preiss D, Jhund PS, Squire I, Cardoso JS, Merkely B, Martinez F, Starling RC, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray JJV, Packer M. Risk related to pre–diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in Heart Failure Trial. Circ Heart Fail 2016;9:e002560. doi:10.1161/CIRCHEARTFAILURE.115.002560

10. McMurray JJ, Gerstein HC, Holman RR, Pfeffer MA. Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. Lancet Diabetes Endocrinol. 2014;2:843–851. doi: 10.1016/S2213-8587(14)70031-2

11. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O’Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P. Heart disease and stroke statistics—2018 update: a report from the American Heart Association. Circulation. 2018;137:e67–e492. doi: 10.1161/CIR.0000000000000558

12. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128. doi: 10.1056/NEJMoa1504720

13. Nauck MA, Tornøe K, Rasmussen S, Treppendahl MB, Marso SP; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Cardiovascular outcomes in patients who experienced a myocardial infarction while treated with liraglutide versus placebo in the LEADER trial. Diab Vasc Dis Res. 2018;15:465–468. doi: 10.1177/1479164118783935

Find this article online on Circ Cardiovasc Qual Outcomes.