Neopterin predicts left ventricular remodeling in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

doi:10.1016/j.atherosclerosis.2010.04.017

Atherosclerosis

Volume 211, Issue 2, August 2010, Pages 574-578

https://doi.org/10.1016/j.atherosclerosis.2010.04.017 Get rights and content

Abstract

Background

Left ventricle remodeling (LVR) is a relatively common and unfavourable event occurring after acute myocardial infarction. A link exists between inflammation and LVR. Neopterin, a marker of inflammation and macrophage activation, is a predictor of left ventricular dysfunction in patients with coronary artery disease. We therefore sought to assess whether both neopterin and brain natriuretic peptide (BNP), a marker of LV dysfunction and patient outcome, correlate with LVR in patients with ST-segment elevation myocardial infarction (STEMI).

Methods

We prospectively assessed 108 STEMI patients (age 64 ± 11 years; 85% male) undergoing primary percutaneous coronary intervention (PCI) who were assessed echocardiographycally assessment was performed at 96 ± 10 h after the onset of symptoms and 12 month after STEMI. LVR was defined as >20% increase in LV end-diastolic volume at 12 months of follow-up compared to baseline. Neopterin and BNP serum concentrations were measured immediately before primary PCI.

Results

At 1 year, 21 patients (19%) showed LVR and 87 (81%) had no LVR. Patients with LVR had higher levels of neopterin at study entry (7.45 ± 1.04 vs 5.19 ± 1.39 nmol/L; p < 0.001). After adjustment for relevant confounders, neopterin levels were found to be an independent predictor of LVR (OR ranging from [3.10, CI 95% 1.928–4.990, p < 0.001] to [3.32, CI 95% 1.999–5.532, p < 0.001]). ROC analysis showed an area under the curve of 0.901 for neopterin (CI 95% 0.84–0.96, p < 0.0001) compared to 0.579 for BNP (CI 95% 0.409–0.748) regarding LVR.

Conclusions

In STEMI patients undergoing primary PCI, high neopterin levels – but not BNP – predict LVR at 1-year follow-up.

Introduction

The development of left ventricular remodeling (LVR) after ST-segment elevation myocardial infarction (STEMI) is relatively common and associated with impaired patient outcome [1]. Early diagnosis of LVR in STEMI patients could lead to more efficient patient management and improved prognosis [2]. Inflammation, in general, and macrophage activation, in particular, may play a major role in LVR. Neopterin has been shown to be elevated in patients with dilated cardiomyopathy [3], [4] and it has also been implicated as a predictor of left ventricular dysfunction in patients with chronic stable angina pectoris [5] and acute myocardial infarction [6]. Experimental studies indicate that proinflammatory cytokines are associated to molecular, clinical, and physiological aspects of LVR [7]. The relationship, however, between increased neopterin levels and LVR has not been assessed systematically in patients with STEMI. We therefore sought to assess whether both neopterin and brain natriuretic peptide (BNP), a marker of LV dysfunction and patient outcome, correlate with LVR in STEMI patients.

Section snippets

Patients

One hundred and fifty patients with first STEMI were admitted into a tertiary care hospital where they received percutaneous coronary intervention (PCI) treatment within 6 h of symptom. The diagnosis of STEMI was established in all patients by the presence of: typical rise and gradual fall (troponin) or more rapid rise and fall (creatine kinase MB) of biochemical markers of myocardial necrosis with at least one of the following: (a) ischemic symptoms; (b) development of pathological Q waves on

Results

Baseline clinical and angiographic characteristic of the entire patient cohort are displayed in Table 1. All patients were treated with primary PCI, and the results were considered successful in 98% of the patients. Twenty-one patients (19%) showed LVR and 87 (81%) had no LVR. Clinical and angiographic variables in patients with and without LVR are shown in Table 2. There were no statistical differences in baseline characteristics, with the exception of neopterin levels (7.45 ± 1.04 vs 5.19 ± 1.39

Discussion

The main and original finding of our study is that neopterin levels on admission were associated with LVR at 12-month follow-up in patients admitted to hospital with first STEMI. LVR was observed in 19% of patients despite of successful primary PCI reperfusion strategies and the systematic use of secondary prevention pharmacologic therapies. This rate of LVR is similar to that reported in previous studies [17] and suggests that factors other than infarct size and infarct-related artery patency

Acknowledgement

The authors thank specially Dr. Alejandro Jimenez-Sosa for assistance with statistical analysis.

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Citation Excerpt :
Neopterin, an aromatic pteridine mainly synthesized by activated monocytes, is a marker of inflammation, immune system activation and an active participant in cardiovascular diseases [9]. Its assessment is proposed as potential tool useful for risk stratification of patients with AMI [10], for prediction of 1-year LV remodeling in patients with ST-segment elevation AMI [11], and as independent predictor of HF hospitalization after an acute coronary syndrome [12]. High serum neopterin levels were found in CHF patients with elevated NYHA class [13] and were associated with high rates of cardiac events in HF patients [14].
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The relationship between neopterin and LV dimensions, NT-proBNP, and pro-inflammatory cytokines were studied in 98 CHF patients, while nineteen healthy subjects were enrolled as controls. Nineteen (19%) patients were in NYHA class I, 38 (39%) in NYHA class II, 27 (28%) in NYHA class III, and 14 (14%) in NYHA class IV.
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We included studies that reported LV volumes or LV diameters as indicators of LV remodeling. Because variability of the data reported (morphologic and biological variables on their original continuous scales or dichotomized into 2 groups) precluded a formal meta-analysis, relations between biomarkers and LV remodeling are presented in Table 1 as positive if a high level of the biomarker was significantly associated (p <0.05) with increased LV remodeling, negative if a low level of the biomarker was significantly associated (p <0.05) with increased LV remodeling, and none in the absence of any significant association.1–59 To visualize the association of a given biomarker with LV remodeling, data were grouped by biomarker; thus, publications that assessed >1 biomarker appear >1 time in Table 1.
Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a high risk of heart failure and death, but LV remodeling remains difficult to predict. Biomarkers may help to refine risk stratification for a more personalized medical approach. They may also shed light on the pathophysiologic processes involved. We performed a systematic review of the published evidence about the association of circulating biomarkers with LV remodeling after MI. We selected 59 publications. Overall, these studies examined 112 relations between 52 different biomarkers and LV remodeling. The biomarkers most consistently associated with LV remodeling were involved in extracellular matrix turnover or neurohormonal activation: matrix metalloproteinase-9, collagen peptides, and B-type natriuretic peptide. This review underscores the vitality of the research on LV remodeling but concludes that the ideal biomarker has not yet been identified. To reach this goal, future studies will have to be larger, have standardized imaging end points, and include replication populations to define optimal cutoffs for LV remodeling prediction. Cardiovascular magnetic resonance appears to be the best technique for LV remodeling assessment but its current availability may be a concern for recruitment for multicenter studies. Recent technologic advances will probably yield new candidate biomarkers of LV remodeling. Tests are necessary to determine whether a multimarker approach would significantly improve risk prediction.
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Neopterin predicts left ventricular remodeling in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Acknowledgement

Am J Cardiol

Immunol Lett

Int J Cardiol

Int J Cardiol

J Am Coll Cardiol

Rev Esp Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Mol Cell Cardiol