Erythropoietin in cardiovascular diseases: exploring new avenues

Cardiovascular disease is an important burden in the Western world, with a prevalence that is increasing exponentially. Indeed, the lifetime risk of coronary artery disease at 40 years of age is 1 in 2 for men and 1 in 3 for women, and it is estimated that one-third of the population worldwide will die of cardiovascular disease, with a majority of these deaths related to MI (myocardial infarction) or the complications of MI. Recent research has suggested that EPO (erythropoietin), an endogenous erythropoietic hormone, may have pleiotropic effects well beyond the maintenance of red blood cells, and may have a cardiovascular role as well, including a potentially salutary effect on reperfusion injury. Although findings supportive of a role of EPO as a cardioprotective agent appear promising, the mechanisms behind the observed benefits remain elusive. In the present issue of Clinical Science, Piuhola and co-workers provide an interesting study that may shed light on the effects of EPO (and possibly related compounds) in the context of acute MI.     

Amino-terminal pro-brain natriuretic peptide, brain natriuretic peptide, and troponin T for prediction of mortality in acute heart failure

BACKGROUND: Combining testing for natriuretic peptides [amino-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP)] and cardiac troponin T (cTnT) may help predict mortality in patients with acute heart failure (HF). METHODS: We studied 209 patients with acute HF at an urban academic center and used ROC curves and multivariate analyses to examine the relationship of outcome to natriuretic peptide and cTnT concentrations at presentation. RESULTS: Higher concentrations of natriuretic peptides and cTnT at presentation were predictors of death at 60 days and 1 year (P <0.001 and P <0.01, respectively, at both time points). Optimal cutoff points for NT-proBNP, BNP, and cTnT for predicting death by 60 days or 1 year were 5562 and 3174 ng/L, 428 and 352 ng/L, and 0.01 and 0.01 microg/L, respectively. Most decedents demonstrated increased concentrations of both natriuretic peptides and cTnT and had a 25% mortality rate at the 60-day time point (P <0.001). Mortality rates were low (<4%) among patients with either no increase or an increase in only 1 marker. Decedents with increases in both a natriuretic peptide and cTnT at presentation had the highest death rate at 1 year (45%, P <0.001). This combination was strongly predictive of death [NT-proBNP plus cTnT: hazard ratio (HR), 7.66; 95% confidence interval (CI), 3.06-17.8; BNP plus cTnT: HR, 6.82; 95% CI, 2.99-16.5]. CONCLUSIONS: A dual-marker strategy incorporating a natriuretic peptide and cTnT is superior to either marker alone for estimating short- and longer-term risk in patients with acute HF.     

Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations

Natriuretic peptide [NP; B‐type NP (BNP), N‐terminal proBNP (NT‐proBNP), and midregional proANP (MR‐proANP)] concentrations are quantitative plasma biomarkers for the presence and severity of haemodynamic cardiac stress and heart failure (HF). End‐diastolic wall stress, intracardiac filling pressures, and intracardiac volumes seem to be the dominant triggers. This paper details the most important indications for NPs and highlights 11 key principles underlying their clinical use shown below.

1. NPs should always be used in conjunction with all other clinical information.
2. NPs are reasonable surrogates for intracardiac volumes and filling pressures.
3. NPs should be measured in all patients presenting with symptoms suggestive of HF such as dyspnoea and/or fatigue, as their use facilitates the early diagnosis and risk stratification of HF.
4. NPs have very high diagnostic accuracy in discriminating HF from other causes of dyspnoea: the higher the NP, the higher the likelihood that dyspnoea is caused by HF.
5. Optimal NP cut‐off concentrations for the diagnosis of acute HF (very high filling pressures) in patients presenting to the emergency department with acute dyspnoea are higher compared with those used in the diagnosis of chronic HF in patients with dyspnoea on exertion (mild increase in filling pressures at rest).
6. Obese patients have lower NP concentrations, mandating the use of lower cut‐off concentrations (about 50% lower).
7. In stable HF patients, but also in patients with other cardiac disorders such as myocardial infarction, valvular heart disease, atrial fibrillation or pulmonary embolism, NP concentrations have high prognostic accuracy for death and HF hospitalization.
8. Screening with NPs for the early detection of relevant cardiac disease including left ventricular systolic dysfunction in patients with cardiovascular risk factors may help to identify patients at increased risk, therefore allowing targeted preventive measures to prevent HF.
9. BNP, NT‐proBNP and MR‐proANP have comparable diagnostic and prognostic accuracy.
10. In patients with shock, NPs cannot be used to identify cause (e.g. cardiogenic vs. septic shock), but remain prognostic.
11. NPs cannot identify the underlying cause of HF and, therefore, if elevated, must always be used in conjunction with cardiac imaging.

     

Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction

Background

Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited.

State of the Art: Newer biomarkers in heart failure

Since natriuretic peptides were successfully integrated into the clinical practice of heart failure (HF), the possibility of using new biomarkers to advance the management of affected patients has been explored. While a huge number of candidate HF biomarkers have been described recently, very few have made the difficult translation from initial promise to clinical application. These markers mirror the complex pathophysiology of heart failure at various levels: cell loss (troponin), fibrosis (ST2 and galectin‐3), infection (procalcitonin), and renal disease (several renal markers). In this review, we examine the best emerging candidates for clinical assessment and management of patients with HF.