Could H-FABP Have Potential Benefits in Diagnostics Beyond Cardiac Health Problems?

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Could H-FABP Have Potential Benefits in Diagnostics Beyond Cardiac Health Problems?

14th March 2019

Could H-FABP Have Potential Benefits in Diagnostics Beyond Cardiac Health Problems?

To date, the most traditional diagnostic test for renal impairment is creatinine. However, although most commonly used, problems can arise when implementing this test as a number of factors are not considered. On this World Kidney Day, Randox will explore the potential utility of H-FABP as a clinical diagnostic marker for cardiac surgery-associated acute kidney injury.

Acute Kidney Injury (AKI) is defined as an acute decline in renal function that can lead to structural changes. It involves a sudden drop in kidney function that usually arises due to a complication of another serious illness such as impaired renal perfusion, exposure to nephrotoxins, outflow obstruction or intrinsic renal disease. As a result, a patient can experience effects such as impaired clearance and regulation of homeostasis, altered acid/base and electrolyte regulation and impaired volume regulation.1

The mortality rate associated with AKI varies depending on severity, patient related factors and setting including whether the patient is in intensive care (ICU) or not.2 In the UK, AKI has been found to affect 1 in 5 people admitted to hospital as an emergency and has been found to be deadlier than a heart attack, contributing to around 100,000 deaths each year. Conversely, in the US, age-standardized rates of acute kidney injury hospitalisations increased by 139% among adults with diagnosed diabetes and by 230% among those without diabetes.3, 4

The rising incidence of AKI comes at price. Patients tend to survive ICU but will be discharged with various degrees of chronic kidney disease (CKD), placing an increasing strain on the health care system. At present, the cost to the NHS is estimated to be between £434 and £620 million, which is more than the costs associated with breast cancer, or lung and skin cancer combined. However, this increased cost and strain could be unnecessary, as research has shown that 30% of the reported 100,000 deaths in the UK could have been prevented with the right care and treatment.3,4

These unfavourable statistics are the result of late detection of AKI, as to date, a superior method of detection has not been found.

Cardiac surgery-associated acute kidney injury (CSA-AKI)

CSA-AKI is a well-recognised postoperative complication of cardiac surgery and is the second most common cause of AKI in the intensive care unit, occurring in up to 30% of patients.5,6 Of these patients, an estimated 1% will require dialysis and the majority will remain dependent on dialysis leading to an increase in mortality. Certain patient groups are more susceptible to CSA-AKI and vulnerability can depend on age, sex, pre-existing cardiac dysfunction, pre-existing CKD, previous cardiac surgery or comorbidity.7

The pathogenesis of AKI involves multiple pathways including hemodynamic, inflammatory and nephrotoxic factors that overlap  leading to kidney injury.6 Figure 1 illustrates the pathophysiology of AKI following cardiac surgery. It shows that there are multiple physiological processes that are associated with the development of AKI as a result of cardiac surgery.8

Figure 1 Illustrates the pathophysiology of AKI following cardiac surgery and the various mechanisms that contribute.8

What is H-FABP?

Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins that are abundantly expressed in tissues with an active fatty acid metabolism, with their primary function being the facilitation of intracellular long-chain fatty acid transport.9 Elevated FABP serum concentrations are related to a number of common comorbidities including heart failure, CKD, diabetes mellitus and metabolic syndrome, which represent important risk factors for postoperative AKI.10

H-FABP is most commonly associated with being a marker for acute coronary syndrome (ACS) as its concentrations peak at approximately 6-8 hours after symptom onset, making it easier to detect. Recently studies have highlighted H-FABP as a potential biomarker for the detection of AKI after cardiac surgery. This potential would mean earlier diagnosis of patients, reducing the mortality rate and costs to the health service.

Potential Mechanism for the release of H-FABP in AKI

There are a number of hypotheses regarding the release of H-FABP, with myocardial injury being considered the major reason for an increased level. The mechanisms involved in this increase have been found to differ depending on the severity of a patients ACS situation including whether they are in ICU.11

One possible explanation for the release of H-FABP is the effects of ischemic stress. Ischemic stress induced by non-cardiogenic shock is a type of mechanical stretching which can lead to the leakage of small amounts of macromolecules. This process would lead to the release of H-FABP into the blood. In non-cardiac patients, minor myocardial injury alone may not adequately explain this observed increase. Other factors such as a reduction in the amount of skeletal muscle tissue, lipid disorders, release of free radicals and an increase in free acids produced by the catabolism of glycogen could also contribute to a rise in H-FABP levels.11

One final process that could lead to increased H-FABP is the damage of vital organ functions which occurs in almost all non-surgical intensive care patients. The degree of leakage of H-FABP may vary depending on the severity of a patient’s condition and whether they have suffered from multiple organ failure or vital organ damage. AKI is a component of multiple organ failure suggesting that serum H-FABP levels may increase in AKI patients as a result. Also, serum H-FABP is excreted by renal tubular cells and patients with an acutely diminished renal function are unable to clear large amounts of H-FABP resulting in increasing levels. These potential mechanisms of H-FABP and its release during AKI provide further confirmation that the measurement of serum H-FABP is an effective biomarker in patients with AKI.11

Comparison of H-FABP Measurement Against Traditional Acute Kidney Disease Measurement Tools

For years, no standard method for definition or diagnosis  was in place for AKI. The RIFLE classification was introduced in 2004, which defined and staged renal failure over seven days into five classes of increasing severity including; risk, injury, failure, loss and end-stage kidney disease.

The RIFLE criteria were then revised by the Acute Kidney Injury Network (AKIN) and introduced four main changes including replacing the period of seven days for serum creatinine (SCr) with forty eight  hours and implementing SCr changes as low as 0.3 mg/dL as the lowest measure considered as AKI. However, despite these changes the Kidney Disease Improving Global Outcome (KDIGO) proposed that AKI is defined when any of the three criteria are met including increase in SCr by 50% in seven days, increase in SCr > 0.3 mg/dL or oliguria.7

However, despite these advances, identification and management of AKI is still difficult for two main reasons. The change of SCr does not occur until two to three days after the initial insult. Also, serum creatinine can rise for a variety of reasons such as tubular injury, hemodynamic alterations or cardio-renal interactions.

The utility of SCr as biomarker for CSA- AKI is questionable as changes occur 48 hours to seven days after the original insult.5 The delays in diagnosis of CSA-AKI may have detrimental effects as prolonging the diagnosis period may result in the disease already being well established.12

Also, a main issue concerning the AKI criteria established is its relevance to the perioperative period. Many surgical patients arrive in hospital without preoperative SCr concentrations being measured, potentially leading to over-diagnosis of AKI. However, when patients do arrive with a preoperative SCr concentration, the opposite can occur and immediate postoperative period SCr concentrations can be lower than baseline as a result of haemodilution.  A comparison of the postoperative and preoperative values can lead to under-diagnosis of AKI and consequently delayed treatment.12

The research conducted has illustrated that SCr is not the most appropriate biomarker for diagnosis of AKI. Studies have demonstrated that H-FABP has more clinical utility and is released less than thirty minutes after myocardial injury and renally excreted within 24 hours, showing that as a biomarker it responds faster than creatinine.12

How Randox can Help

The Randox H-FABP test tests utilises an immunoturbidimetric method, offers a wide measuring range and is available liquid ready-to-use for convenience and ease of use.

Want to know more?

Contact us or visit the Randox H-FABP Site

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  • References

    1. National Kidney Foundation. Acute Kidney Injury (AKI). National Kidney Foundation. [Online] National Kidney Foundation. [Cited: February 3, 2019.] https://www.kidney.org/atoz/content/AcuteKidneyInjury.
    2. Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges. Geus, de, MG, Betjes and J , Bakker. 2, s.l. : NCBI, 2012, Vol. 5.
    3. Kidney Care UK. A range of useful facts and stats about kidneys. Kidney Care UK. [Online] Kidney Care UK. [Cited: February 15, 2019.] https://www.kidneycareuk.org/news-and-campaigns/facts-and-stats/.
    4. Centers for Disease Control and Prevention. Trends in Hospitalizations for Acute Kidney Injury — United States, 2000–2014. Centers for Disease Control and Prevention. [Online] Centers for Disease Control and Prevention, March 16, 2018. [Cited: February 22, 2019.] https://www.cdc.gov/mmwr/volumes/67/wr/mm6710a2.htm.
    5. Cardiac Surgery-Associated Acute Kidney Injury. Mao, h, et al. s.l. : Karger, 2013, Vol. 3.
    6. Acute Kidney Injury Associated with Cardiac Surgery. Rosner, Mitchell and Okusa, Mark. 1, s.l. : Clinical Journal of American Society of Nephrology, 2016, Vol. 1.
    7. Cardiac surgery-associated acute kidney injury. Loubon, Christian, et al. 4, s.l. : NCBI, 2016, Vol. 19.
    8. Acute kidney injury following cardiac surgery: current understanding and future directions. O’Neal, Jason, Shaw, Andrew and Billings, Frederic. s.l. : NCBI, 2016, Vol. 20.
    9. Heart-type fatty acid-binding protein predicts long-term mortality after acute coronary syndrome and identifieshigh-risk patients across the range of troponin values. Kilcullen, N, et al. 20, s.l. : Epub, 2012, Vol. 50.
    10. Preoperative serum h-FABP concentration is associated with postoperative incidence of acute kidney injury in patients undergoing cardiac surgery. Oezkur, Mehmet, et al. 117, s.l. : BMC Cardiovascular Disorders, 2014, Vol. 14.
    11. The serum heart-type fatty acid-binding protein (HFABP) levels can be used to detect the presence of acute kidney injury on admission in patients admitted to the non-surgical intensive care unit. Shirakabe, A, et al. 1, s.l. : NCBI, 2016, Vol. 16.
    12. Perioperative acute kidney injury. Goren, O and Matot, I. 2, s.l. : British Journal of Anaesthesia, 2015, Vol. 115.

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Your heart is amazing. Not only is it your most critical organ but also one of the most hard-working. The average adult heart beats around 100,000 times a day, acting as a giant pump for all the blood in your body. Indeed, every day your heart pumps over nine litres of blood through a system of blood vessels over 60,000 miles long – it’s little wonder, then, the importance placed on looking after such a vital muscle.

The heart works 24/7, only taking a rest when you sleep with the natural drop of heart rate and blood pressure. Over time, and influenced by lifestyle choices, the heart grows weaker, needing to work harder to fulfil its function. Crucial lifestyle changes now could limit your risk of developing serious cardiac conditions, such as Cardiovascular Disease (CVD) in the future. Factors which can contribute to your CVD risk include genes inherited from parents or grandparents, smoking, an unhealthy diet, excessive alcohol consumption and low physical activity levels.

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Today in the UK, 530 people will go to the hospital with a suspected heart attack. Only a fifth of these people will actually be having a heart attack. According to a team from King’s College London, as reported by the BBC, a faster, more accurate diagnosis of whether chest pain is caused by a heart attack would save the health service millions of pounds each year by sending well patients home and freeing up beds. Yet current testing methods do not efficiently differentiate between high-risk patients and the estimated 80% of patients who are not having a heart attack.

Randox’s revolutionary test for Heart-Type Fatty Acid-Binding Protein (H-FABP), when combined with current testing, is able to rule out a heart attack for patients who present at A&E with chest pain which is caused by other conditions such as respiratory issues, meaning they may not need emergency admission.

When measured at the time a patient presents to A&E with chest pain, H-FABP enables doctors to triage patients suffering with a heart attack more efficiently than before, making sure those at high-risk are given medical intervention earlier.

Early screening in the form of a comprehensive health check is essential to detect cardiac irregularities before they become serious problems. Heart damage builds up over time, meaning that when detected early enough, lifestyle changes can help to reduce cardiac risk and potentially even prevent a cardiac event occurring.

Therefore, it is vitally important that individuals are tested for CVD to detect them in the earliest stages to reduce damage, prevent further damage, or even death.  Furthermore, many people suffer from inherited cardiac risk factors, which stresses the need for accurate testing.

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The RIQAS Liquid Cardiac EQA programme is designed to monitor the performance of up to 9clinically significant cardiac markers including: CK-MB mass, D-dimer, Digoxin, homocysteine, hsCRP, myoglobin, NT proBNP, troponin I, and troponin T.  RIQAS is ISO/IEC 17043 accredited and allows the registration of up to five instruments at no extra cost.  All samples are 100% human serum and provided in a liquid ready-to-use format for enhanced convenience.  Submit your results bi-weekly and view reports online via RIQAS.Net.  For more information on RIQAS, the world’s largest international EQA scheme, please click here or email acusera@randox.com

 

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Heart attack test H-FABP 12 times faster than current methods

As the supplier of a pioneering diagnostic able to assist with differentiating between coronary pain and non-cardiac chest pain, Randox Laboratories has this week welcomed news about the importance of introducing new innovations which can significantly improve patient outcomes.

Prioritising people presenting with a heart attack over those with non-cardiac chest pain is one of the biggest challenges A&E doctors face – there are around 200,000 heart attacks each year in the UK, but around 1 million people come to A&E with chest pains.  According to a team from King’s College London, as reported by the BBC, a faster, more accurate diagnosis of whether chest pain is caused by a heart attack would save the health service millions of pounds each year by sending well patients home and freeing up beds. Yet current testing methods do not efficiently differentiate between high-risk patients and the estimated 80% of patients who are not having a heart attack.

Randox’s revolutionary test for Heart-Type Fatty Acid-Binding Protein (H-FABP) however, when combined with current testing, is able to rule out a heart attack for patients who present at A&E with chest pain which is caused by other conditions such as respiratory issues, meaning they may not need emergency admission.

When measured at the time a patient presents to A&E with chest pain, H-FABP enables doctors to triage patients suffering with a heart attack more efficiently than before.

Dr. Gary Smyth, Medical Director at Randox Laboratories, hopes that more efficient testing will become widely available so that doctors can identify and prioritise patients at risk;

“Despite the best efforts of our NHS colleagues, EDs across the UK are under tremendous pressure.  In many cases people are presenting with chest pain but aren’t suffering from a heart attack, and given that current cardiac tests are not as sensitive as clinicians would like, these patients are being admitted unnecessarily, taking up beds and valuable resources.

 “It is imperative that newer, faster tests are adopted because fundamentally this means saving lives.”

H-FABP is released into the bloodstream within 30 minutes of a heart attack, whereas people who are currently admitted to hospital with chest pains may have to wait several hours for test results.  Even the latest heart attack test to be adopted by the NHS, troponin, can take up to six hours to provide confirmation.

H-FABP, conversely, is released from the heart during the early stages of a heart attack and because it is so small, it can be detected when the heart cells are being damaged, rather than at the stage when troponin would usually be detected – when cell death has already occurred.  The test can also be used to identify people who are at high risk of heart attack in the near future.

Dr. Peter FitzGerald, Founder and Managing Director of Randox Laboratories, commented;

“Research shows that patients who were troponin negative and therefore sent home from hospital, but who were positive for H-FABP, were at high risk of death – as high as a 20% chance of death that same year.

 “If the H-FABP test was added to existing tests upon arrival at hospital, doctors could quickly and accurately rule out the 80% of chest pain patients who are not having a heart attack, allowing resources to be focused on those who are actually at high risk.”

For further information on H-FABP, please visit https://www.randox.com/h-fabp/, or contact the Randox PR team by phoning (0) 28 9442 2413 or emailing randoxpr@randox.com


Randox Reagents: Solving the Problem of Heart Attack Misdiagnosis

A report has today revealed that almost a third of patients in England and Wales are being given a misdiagnosis following a heart attack, following a study of 243 NHS hospitals, conducted by researchers at Leeds University.

Timely evaluation of patients with chest pain and subsequently suspected heart attack is a major challenge for hospitals around the world, with chest pain typically representing around 5% of all visits to the Emergency Department (ED) and 25% of ED admissions. One of the biggest challenges facing emergency doctors now is how to prioritise people presenting with chest pain – to primarily deal with those suffering from a heart attack, and to be able to move those who are not, to a different ward, to alleviate the pressures of the overrun A&E departments.

Responding to the escalating misdiagnosis crisis in emergency hospitals across the globe, scientists at Randox Laboratories in the UK have developed a test which could help clinicians rule out heart attacks in patients immediately upon arrival at hospital; allowing clinicians to accurately prioritise those who have truly suffered heart attacks.

This Randox test, for Heart-type fatty acid-binding protein (H-FABP), is a highly sensitive biomarker for use in the earlier diagnosis of patients with suspected Acute Myocardial Infarction (AMI), enabling faster “rule-in” and “rule-out”. H-FABP is detectable as early as 30 minutes after chest pain onset, significantly earlier than traditionally used biomarkers such as Troponin or CK-MB , which typically require 6-12 hours to reach detectable concentrations.

Put simply, given that H-FABP is released earlier than traditional biomarkers used in diagnosing a heart attack, an earlier diagnosis is achievable.  

A succession of recent international clinical trials have demonstrated that by combining H-FABP, via this new laboratory assay, with the existing tests already used in hospitals for for Troponin I or Troponin T, the sensitivity and negative predictive value for ruling out AMIs is significantly improved.

Growing evidence indicates that even when one of the newer generation of “highly sensitive” Troponin assays is used, utilising the combination of Troponin and H-FABP is superior to Troponin alone.

The value of H-FABP is not just in positive diagnosis – but doctors are beginning to see it as a means of ‘ruling out heart attack’ when a patient presents at A&E with chest pain.

 

Please do get in touch if you would like to find out more about our H-FABP test, and how this can go a long way in solving the heart attack misdiagnosis crisis, by emailing reagents@randox.com


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