Risk Stratification of Patients with Acute Coronary Syndrome and Congestive Heart Failure

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Acute coronary syndrome (ACS) and congestive heart failure (CHF) are significant health risks affecting a large part of the population. In both diseases, early detection and initiation of treatment significantly reduce the risk of serious adverse events and death. B-type natriuretic peptide (BNP) and myeloperoxidase (MPO) have both shown considerable utility in the early diagnosis of patients with these conditions, as well as the ability to risk-stratify these patients. BNP, while initially identified as a marker of severity of heart failure, has recently demonstrated its ability to aid in the risk stratification of ACS patients. MPO has been identified as an early indicator of myocyte necrosis and a marker of risk for developing and worsening heart failure.

B-type Natriuretic Peptide as a Prognostic Tool in Acute Coronary Syndrome

While BNP is primarily used for the diagnosis of heart failure, many studies have been performed recently showing the prognostic value of BNP after hospitalisation for ACS. In the ACS setting, BNP levels most likely rise due to acute left ventricular stiffening as a result of myocardial ischaemia. In patients admitted to hospital with non-ST-elevation or ST-elevation myocardial infarctions (MIs), BNP levels above 80pg/ml were associated with a two-fold increased risk of death within two years. Additionally, these patients were at higher risk of new-onset or worsening CHF.1 Measurement of BNP levels in the months following presentation with ACS also appears to be important in risk stratification of these patients. Patients who had normal BNP levels at presentation but who demonstrated elevated BNP levels four months later were shown to be at a significantly higher risk of death or new-onset CHF than patients with high initial and low follow-up BNP levels.1

Myeloperoxidase – An Early Diagnostic Marker of Acute Coronary Syndrome

MPO is a haemoprotein that is involved in inflammatory processes. In acute coronary syndrome, MPO has emerged as an early marker of myocyte necrosis. The activation of leukocytes that occurs in patients with ACS is responsible for initiating the secretion of MPO.2 MPO degrades the protective collagen coating of plaques, causing them to become vulnerable to erosion and rupture.3 Additionally, MPO alters the characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) by binding to apolipoprotein A1, causing oxidation and subsequently resulting in the destabilisation of plaques.3 The oxidative effects of MPO on HDL cause HDL molecules to become pro-inflammatory and pro-atherogenic. This contributes to the formation of atherosclerotic lesions.4 MPO has been implicated as a mechanistic link between inflammation and plaque instability, and therefore is believed to be a useful marker for predicting cardiovascular event risk.2

Clinical studies have shown that MPO levels are higher in patients with coronary artery disease (CAD) than in normal controls.3 MPO levels have been shown to increase within two hours of symptom onset, which is much earlier than the other markers of myocardial necrosis: troponin and creatine kinase cardiac muscle (CK-MB). In an emergency department (ED), patients who had negative initial troponin T (TnT) levels that became positive within four to 16 hours or abnormal initial MPO levels were able to predict an MI within 16 hours of presentation.2 The ability of MPO to rapidly identify acute coronary syndrome in patients with chest pain suggests that it may play a vital role in initiating treatment and minimising damage to the myocardium.2

MPO levels may also have significant long-term prognostic value. Data from the CAPTURE trial showed that ACS patients who had MPO levels higher than 350μg/l were significantly more likely to have an MI or die within six months (adjusted hazard ratio 2.25) than those with MPO levels below this threshold. Patients with negative TnT and high MPO levels were at a greater cardiac risk than those with negative TnT and low MPO. Therefore, MPO levels may assist physicians in risk-stratifying patients with undetectable TnT levels.2 The utility of MPO to predict the advance of CAD was tested using carotid ultrasound in patients with no recent symptoms of carotid artery disease. This study showed that higher initial MPO levels correlated with a higher frequency of progression of carotid artery stenosis over nine months.4 In a study of patients in the ED with chest pain, Brennan et al. found that major adverse events after 30 days and six months were more frequent with increasing quartiles of MPO.3

The relationship between MPO and HDL may also be useful in the risk stratification of patients with and without ACS. Patients with high MPO (>310μg/l) and low HDL (<49μg/l) levels showed more frequent progression of stenosis than those with high MPO/high HDL or low MPO/low HDL levels. Patients with high MPO and high HDL had no increased risk of stenosis progression compared with the other groups.4 These results suggest that the measurement of MPO may help clinicians risk-stratify patients with low HDL. When used in collaboration, these two tests may provide insight into an individual’s risk of developing coronary artery disease.

B-natriuretic Peptide – A Diagnostic and Prognostic Biomarker in Congestive Heart Failure

BNP has become a widely used tool for faster, more accurate diagnosis of heart failure. Many studies have shown that BNP levels are much higher in patients who have CHF, and that levels are significantly higher in the presence of decompensated heart failure. Investigators in the Breathing Not Properly study identified a cut-off point of 100pg/ml for differentiating heart-failure-related dyspnoea from other causes.5 BNP levels are frequently used in the hospital setting for risk-stratifying patients and tailoring treatment. BNP levels have been shown to correlate with pulmonary capillary wedge pressures (PCWPs) in response to left ventricular stretch due to volume overload, and in some cases can be used as adjuncts to or substitutes for Swan–Ganz catheter measurements.6

BNP levels on discharge from the hospital are good indicators of whether a patient’s fluid status has been optimised. Additionally, these levels provide insight into the patient’s prognosis in the months and years following discharge. In a study of patients admitted for CHF exacerbations, those whose discharge BNP levels fell below 430pg/ml had a relatively low likelihood of being re-admitted within the following 30 days.7 These findings are similar to results from a recent study by Bettencourt et al., who found that failure of BNP levels to fall during hospitalisation predicted death/re-hospitalisation, and that discharge levels <250pg/ml predicted event-free survival.8

There are several caveats to using BNP. Patients with chronic kidney disease exhibit significantly higher BNP levels than those with normal kidney function. Plasma BNP levels were found to correlate with creatinine levels, suggesting that BNP levels increase with worsening renal function.9 Obesity is another condition that affects interpretation of BNP levels. An inverse relationship between BNP and body mass index (BMI) has been demonstrated in many studies. Daniels et al. demonstrated this finding in a subanalysis of the Breathing Not Properly study and determined optimal cut-off points for diagnosis of CHF based on BMI: 170pg/ml for lean (BMI <25); 110pg/ml for overweight/obese (25 ≤ BMI < 30); and 54pg/ml for morbidly obese patients (BMI ≥35).10

The Role of Myeloperoxidase in Progression of Congestive Heart Failure

MPO offers some interesting hypotheses regarding the progression of CHF. MPO accumulates and causes increased plasmin generation in areas of infarction.11 Therefore, it is thought that MPO is responsible for impaired cardiac remodelling after myocardial infarction and inflammation.11 In order to examine the role of MPO in CHF, Tang et al. studied patients with heart failure and found MPO levels to be significantly higher in patients with CHF than in controls. MPO levels were also found to correlate with BNP levels, suggesting that MPO levels are useful in the risk stratification of heart failure. Additionally, increasing levels of MPO have been shown to be associated with worsening severity of heart failure.12 However, MPO levels have been shown to be useful predictors of heart failure independent of BNP levels. When MPO levels were adjusted for age and BNP, increasing quartiles of MPO still correlated with an increasing risk of heart failure.12 Although MPO appears to be an accurate indication of severity of heart failure, its clinical utility is of uncertain significance.


Both BNP and MPO have shown strong clinical utility in the diagnosis and management of ACS and CHF. Use of these biomarkers in addition to the classic diagnostic markers and tests such as troponin, CK-MB and echocardiography increases the accuracy with which clinicians make diagnoses and helps them to risk-stratify patients in order to optimise treatment. However, further investigation is needed to expand our knowledge of the role of MPO in heart failure.


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