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NT-proBNP Levels Influence the Prognostic Value of Mineral Metabolism Biomarkers in Coronary Artery Disease.

ABSTRACT:

Background

Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet. The objective of this study is to assess the influence of NT-ProBNP on the prognostic role of MM markers in patients with SCAD.

Methods

We analyzed the prognostic value of MM markers (parathormone (PTH), klotho, phosphate, calcidiol (25-hydroxyvitamin D₃), and fibroblast growth factor-23) in 964 patients with SCAD and NT-ProBNP > 125 pg/mL vs. patient with NT-ProBNP ≤ 125 pg/mL included in five hospitals in Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack).

Results

A total of 622 patients had NT-proBNP > 125 pg/mL and 342 patients had NT-ProBNP ≤ 125 pg/mL. The median follow-up was 5.1 years. In the group of NT-proBNP > 125 pg/mL, the patients were older, and there were more females and smokers than in the group of patients with normal NT-proBNP. Additionally, the proportion of patients with hypertension, atrial fibrillation, ejection fraction < 40%, cerebrovascular attack, or prior coronary artery bypass graft was higher in the high NT-proBNP group. In the high NT-proBNP patients, the predictors of poor prognosis were PTH (HR = 1.06 (1.01-1.10), p < 0.001) and NT-proBNP (HR = 1.02 (1.01-1.03), p = 0.011), along with age (HR = 1.039 (1.02-1.06), p < 0.001), prior coronary artery bypass graft (HR = 1.624 (1.02-2.59), p = 0.041), treatment with statins (HR = 0.32 (0.19-0.53), p < 0.001), insulin (HR = 2.49 (1.59-4.09), p < 0.001), angiotensin receptor blockers (HR = 1.73 (1.16-2.56), p = 0.007), nitrates (HR = 1.65 (1.10-2.45), p = 0.014), and proton pump inhibitors (HR = 2.75 (1.74-4.36), p < 0.001). In the NT-proBNP ≤ 125 pg/mL subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol (HR = 1.01 (1.00-1.02), p = 0.014) and calcidiol (HR = 0.96 (0.92-0.99), p = 0.045), as well as treatment with verapamil (HR = 11.28 (2.54-50.00), p = 0.001), and dihydropyridines (HR = 3.16 (1.63-6.13), p = 0.001).

Conclusion

In patients with SCAD and NT-ProBNP > 125 pg/mL, PTH and NT-ProBNP, which are markers related to ventricular damage, are predictors of poor outcome. In the subgroup of patients with NT-ProBNP ≤ 125 pgm/L, calcidiol and non-HDL cholesterol, which are more related to vascular damage, are the independent predictors of poor outcome. Then, in patients with SCAD, baseline NT-ProBNP may influence the type of biomarker that is effective in risk prediction.

SUBMITTER: Martinez-Milla J

PROVIDER: S-EPMC9319637 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Glutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP. METHODS:Substudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M L-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP. RESULTS:Overall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II???4.15; glutamate group n?=?56; control group n?=?45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995-6260] vs. 6745 [3455-12,687] ng•L-1, p?=?0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426-7423] vs. 8430 [5370-14,100] ng•L-1, p?=?0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p?=?0.002). Patients in the glutamate group also had shorter ICU stay (21 [19-26] vs. 25 [22-46] h, p?=?0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170-500] vs. 560 [210-910] ng•L-1, p?=?0.025). CONCLUSIONS:Post hoc analysis of postoperative NT-proBNP suggests that intravenous infusion of glutamate may prevent or mitigate myocardial dysfunction in high-risk patients undergoing CABG. Further studies are necessary to confirm these findings. Trial registration Swedish Medical Products Agency 151:2003/70403 (prospectively registered with amendment about this substudy filed March 17, 2007). ClinicalTrials.gov Identifier: NCT00489827 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=1&rank=1.