Additive prognostic value of plasma N-terminal pro-brain natriuretic peptide and coronary artery calcification for cardiovascular events and mortality in asymptomatic patients with type 2 diabetes

Abstract

Background: In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline.

Methods: Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP > 45.2 ng/L and/or CAC ≥ 400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median).

Results: High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31).

Conclusions: In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.

Fig. 1

Selection of the study population and algorithm used for risk group assessment with the use of plasma NT-proBNP and coronary artery calcium score (CAC). * (i) patients with P-NT-proBNP >45.2 ng/L underwent myocardial perfusion imaging. Patients with abnormal myocardial perfusion imaging (n = 55) or CAC >100 (n =29) were referred for coronary angiography; (ii) patients with P-NT-proBNP ≤ 45.2 ng/L and CAC 400–1000 underwent CT angiography (n = 20); CT angiography was only used in patients with CAC 400–1000 since severe coronary artery calcifications (CAC > 1000) compromise the validity of CT angiography. Patients with abnormal CT angiography were referred for coronary angiography (n =15) and (iii) patients with P-NT-proBNP ≤ 45.2 ng/L and CAC >1000 underwent myocardial perfusion imaging (n =9). Patients with abnormal myocardial perfusion imaging (n = 6) were referred for coronary angiography.**Significant coronary artery disease was defined as the presence of one or more significant myocardial perfusion defects on myocardial perfusion imaging, and/or one or more significant major epicardial coronary artery stenosis at coronary angiography

Fig. 2

a Kaplan-Meier survival function estimates for risk of combined cardiovascular events by categorisation into low- and high-risk at baseline. Hazard ratio 11.4 (95 % confidence interval 2.7-47.3); p < 0.0001. b Kaplan-Meier survival function estimates for risk of all-cause mortality by categorisation into low- and high-risk at baseline. Hazard ratio 6.4 (95 % confidence interval 1.5-27.1); p = 0.004

Fig. 3

The continuous risk functions cover the 5^th to 95^th percentile interval of the coronary artery calcium score and correspond to levels of NT-proBNP at 7, 20, 55, 148, 403 ng/L (approximate the 5^th, 25^th, 50^th, 75^th and 95^th percentiles of the distribution). Risk functions were fitted by Cox regression with adjustment for sex, age, smoking, LDL and HDL cholesterol, HbA1c, eGFR, systolic blood pressure and urinary albumin excretion rate at baseline