Table 2 Natriuretic peptides and prediction of death and cardiovascular outcomes in patients with T2DM

Gaede et al. [66]

160 patients with T2DM, age 52–58 y; 60% males; with microalbuminuria

ASCVD

7–8 years

NT-proBNP above and below median 33.5 pg/mL

HR 95% (CI)

3.6 (1.7–7.5)

Tarnows et al. [70]

363 patients with T2DM, age 50–58 y; 72% male caucasians; 6.6% with CHD; 1.5% with HF

CV mortality

9 years

NT-proBNP: T1 < 41 pg/mL vs. T3 > 103 pg/mL

HR 95% (CI)

2.26 (1.27–4.02)

Huelsmann et al. [76]

631 unselected patients with T2DM; age 58.5 ± 13.9 y; 44.7% female; 22.8% with history of any CVD

Unplanned hospitalization for CV events or death

12 months

NT-proBNP > 125 pg/mL

The area under the ROC curve was 0.785 in the prediction of unplanned hospitalizations for CV events or death. The negative predictive value of NT-proBNP < 125 pg/mL for short-term CV events was 98%

Casale-Monferrato et al. [71]

1825 patients with T2DM, age 67.6 ± 10.5 y; no clinical evidence of heart failure

All-cause and CV mortality

5.5 years

NT-proBNP > 91 pg/mL

HR 95% (CI)

2.05 (1.47–2.86) for all-cause death and 4.47 (2.38–8.39) for CV death

ADVANCE [74]

3862 patients with T2DM, 66.9 ± 6.61 y, 61% male

CV events and death

5 years

Log-linear association between NT-proBNP and outcomes

The net reclassification index was increased by 39% with the addition of NT-proBNP to the multivariate risk prediction model for CV events and by 41% for death

SunMACRO [67]

851 patients with T2DM and nephropathy, 64 ± 9 y, 76% males

Renal and CV events

Mean (SD) follow-up was 11.2 (6.6) months in the sulodexide group and 10.7 (6.6) months in the placebo group

NTproBNP > 407 pg/mL for CV outcome, > 973 pg/mL for renal outcome

C statistic for CV events was improved by adding NT-proBNP to the multivariable model (0.722 vs. 0.658, P = 0.018)

ELIXA [9]

5525 patients with T2DM and acute coronary event-related hospital admission within 180 days. Placebo group 60.6 ± 9.6 y, intervention group 59.9 ± 9.7 y, 69.3% males, 75.2% whites

CV death, MI, stroke, or hospitalization for unstable angina

26 months

Group without CV events: BNP = 95 (92–98), NT-proBNP = 285 (274–295) vs. group with CV events: BNP = 198 (184–213), NT-proBNP = 703 (644–766) (pg/mL)

BNP or NT-proBNP alone predicted death equally well as all other variables combined (C-statistics: 0.77 vs. 0.77)

ALTITUDE [10]

5509 high-risk patients with T2DM, 64 ± 6.8 y, 67% males 56% whites

All-cause death, CV composite outcome

2.6 years

NT-proBNP deciles

NT-proBNP by itself was similar to a 20-variable model in predicting both death and CV events

Prausmüller et al. [11]

1690 patients with T2DM, 63 y, 54% male, 10 y of T2DM duration

CV and all-cause death and CVD and all-cause hospitalizations

10-year follow up for fatal CVD and all-cause death and a 5-year follow up for CVD and all-cause hospitalizations

NT-proBNP > 125 pg/mL, and NT-proBNP tertiles (1st tertile: 59 pg/mL [IQR 59–59], 2nd tertile: 122 pg/mL [IQR 90–156], 3rd tertile: 376 pg/mL [IQR 267–648])

NT-proBNP was superior to the ESC/EASD risk model for all outcomes (C-index: CVD hospitalization: 0.74 vs. 0.54; all-cause hospitalization: 0.62 vs. 0.55; p < 0.001 for all comparisons)

ORIGIN [12]

8401 people with CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or T2DM, 63.2 ± 7.9 y, 66.1% males

CV composite outcome (myocardial infarction, stroke, HFH, and CV death), all-cause death, and CV death

6.2 years

NT-proBNP categories (< 128; 128–401; 402–808, 809–1730, > 1740 pg/mL)

For each increase in NT-proBNP by one level the HR increased 53% for the composite CV outcome, 48% for death, and 65% for CV death. The C-statistic of NT-proBNP by itself was similar to that of the multivariate model for any outcome