The burden of cardiovascular disease in India
Recent evidence has reported the incidence of cardiovascular disease (CVD) to be 50% to 400% higher in Asian Indians than individuals of other ethnic origins. In addition, some 30% to 40% of cardiovascular deaths occur between 35 and 64 years of age. An estimated 9.2 million productive years of life were lost to cardiovascular disease in India in 2000, a number that is expected to increase to nearly 18 million by 2030 (10 times the rate in the U.S.). The prevalence of heart failure in India due to coronary heart disease, hypertension, obesity, diabetes and rheumatic heart disease to range from 1.3 to 4.6 million, with an annual incidence of 491 600-1.8 million.
Biomarkers in cardiology: The current gold standard and its limitations
Several biomarkers are in use for diagnosis, monitoring and prognostication of cardiovascular disorders. Natriuretic peptides (NPs) represent the current gold standard with respect to biomarker applications in cardiology. While the NPs are the present (and likely future) gold standards, limitations for their current use exist. Neither BNP nor NT-proBNP is perfect tool for prognostication, and their levels are affected by many other conditions in addition to heart failure. Furthermore, other conditions associated with adverse outcomes, including progressive myocardial necrosis, inflammation and fibrosis, are all present in varying degrees among patients with heart failure; and neither BNP nor NT-proBNP can identify them. Thus, the development and use of biomarkers to better understand the complex pathophysiology in heart failure will be necessary to compliment BNP and NT-proBNP.
A novel promising biomarker for monitoring and prognosis of heart failure patients
In this regard it is noteworthy to mention ST2 which is a widely accepted biomarker for prognosis and risk stratification of heart failure patients and is highly specific to the cardiac tissue. sST2 protein is independent of traditional factors, such as age and BMI, which usually affect levels of NT-proBNP
ST2 (for growth STimulation expressed gene 2; also known as IL1RL1, or Interleukin 1 Receptor-Like 1) is a member of the interleukin 1 receptor family. The ST2 protein has two isoforms directly implicated in the progression of cardiac disease: a soluble form (referred to as soluble ST2 or sST2) and a membrane-bound receptor form (referred to as the ST2 receptor or ST2L).
The ligand for ST2 is the cytokine Interleukin-33(IL-33). Binding of IL-33 to the ST2 receptor, in response to cardiac disease or injury, such as an ischemic event, elicits a cardioprotective effect resulting in preserved cardiac function.
This cardioprotective IL-33 signal is counter-balanced by the level of soluble ST2, which binds IL-33 and makes it unavailable to the ST2 receptor for cardioprotective signaling. As a result, the heart is subjected to greater stress in the presence of high levels of soluble ST2, leading to cellular death and tissue fibrosis, reduced cardiac function, and increasing the rate of disease progression.
Multiple published studies have demonstrated that the level of ST2 in blood can help a physician better predict a patient's prognosis, and thus make better treatment decisions than solely employing clinical parameters and existing laboratory assays.
ST2: An overview of clinical utility
The ideal clinical situation for using ST2 is for prognostication, risk stratification and mortality prediction of a patient with acute decompensated HF. sST2 has been considered as a possible biomarker in dyspnoeic patients with and without acute destabilized HF referred to the emergency department. Notably high levels of ST2 are seen in chronic HF patients. Determining ST2 plasma levels in chronic HF patients can drive therapy decision making and predictions of clinical outcomes. A combination of ST2 with other well established markers like NPs, troponins and CRP can further augment the prognosis and risk stratification in HF patients. Patients with ST2 >35 ng/ml have a 2.8x higher risk of adverse outcomes within 30 days than patients with low ST2 concentrations. The relative risk of adverse events in patients with ST2 > 35ng/ml persists at a level of at least 1.8 for a follow up period of 4 years. Patients with a greater decrease in sST2 during serial monitoring (baseline & week 2) have better outcomes at one year than patients with smaller change in sST2, independent of NT-proBNP concentration.
ST2: The regulatory status and endorsement by guidelines
The American College of Cardiology Foundation/American Heart Association Task Force jointly released its expanded clinical practice guideline for the management of patients with heart failure and has identified ST2 "not only predictive of hospitalization and death in patients with HF [heart failure] but also additive to natriuretic peptide levels in its prognostic value." In 2011, the US FDA had also provided its approval to the use of presage ST2 as a biomarker for prognosis of chronic heart failure.