Background
Physiology and pathophysiology of natriuretic peptides
NP in the regulation of energy metabolism and diabetes
Effect of clinical comorbidities on NP levels
Age, sex, and race
Obesity
Risk of new-onset diabetes
Can measurements of NP guide treatment in patients with diabetes?
Impact of diabetes treatment on NP concentrations
Metformin
Pioglitazone
DPP4 inhibitors
SGLT2 inhibitors
GLP-1 RA
Sulfonylureas
Insulin
Clinical parameter | Effect on circulating BNP/NT-proBNP |
---|---|
Age | Increase [23] |
Female gender | Increase [23] |
African Americans | Decrease [24] |
Obesity | |
Hypertension | Increase [52] |
Coronary heart disease | Increase [53] |
Left ventricular systolic dysfunction | |
Atrial fibrillation | Increase [55] |
Renal insufficiency | Increase [56] |
Hepatic disease | Increase [57] |
Metformin | |
Pioglitazone | |
DPP-4i | Unchanged [41] |
SGLT2 inhibitors | |
GLP-1 RA | |
Sulfonylureas | Increase [50] |
Insulin | |
ACE inhibitors | Decrease [58] |
Beta-blockers |
NT-proBNP in risk stratification
Patients without known CVD
Patients with type 2 diabetes and CVD
Patients with type 2 diabetes and CKD
Mortality in type 2 diabetes
NT-proBNP in death and CVD prediction
Are we ready to use NT-proBNP values in death and CV outcomes risk stratification?
Study or author | Baseline population | Outcome | Follow-up | Cut-off/average | Predictive analysis |
---|---|---|---|---|---|
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 |