Tests that look at changes in biochemistry have an important application in medicine, including point-of-care cardiac testing and monitoring heart failure. Biochemical tests can also be used to determine if an individual is at risk of certain diseases, including cardiovascular disease.
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How are biochemical tests used to monitor heart disease?
Acute myocardial infarction
Acute myocardial infarction, where the blood supply to cardiac myocytes is compromised leading to cardiac myocyte death, is an important disease that results in morbidity and mortality across the world. Despite this, it is a condition that is often misdiagnosed, leading to either unnecessary death or inappropriate hospitalization. Therefore, it is important to establish a quick, reliable test that can accurately diagnose patients.
Currently, the diagnosis of myocardial infarction is typically achieved through the presence of symptoms such as chest pains and the use of ECG and cardiac troponin assay, which look for damage to the heart muscle. While cardiac troponin assay is a good biochemical test, it is thought that there is a delay in the increase of circulating cardiac troponins of around 3-4 hours.
This means that to ensure accurate diagnoses, this test needs to be repeated multiple times over 6-12 hours, which impacts how quickly treatment can be started. High-sensitivity cardiac troponin testing has become available, but an unexpected result of this was the discovery of other cardiac conditions.
Researchers have, therefore, been investigating other molecules that could potentially be used as a diagnostic test for acute myocardial infarction. One potential candidate for such a biochemical test is a heart-type fatty acid-binding protein (H-FABP). H-FABP is a small protein that is found in cardiac myocytes, and its small size and solubility mean that it is released faster from the cardiac myocytes compared to cardiac troponins.
Xu and co. carried out a meta-analysis investigating whether H-FABP is a good biomarker that can be used in a biochemical test for early diagnosis of acute myocardial infarction. Here, the authors looked at the results from 22 studies, which included a cumulative total of 6602 patients. The authors concluded that H-FABP testing is moderately accurate at diagnosing acute myocardial infarction between 3-6 hours after the onset of symptoms. However, when used in conjunction with high-sensitivity cardiac troponin testing, the sensitivity of the diagnostic testing was improved.
Heart failure is when the heart stops functioning effectively, leading to symptoms such as shortness of breath and fatigue. A biochemical test looking at the levels of B-type natriuretic peptide (BNP) has been used to diagnose and monitor patients with heart failure.
BNP is a peptide hormone, whose functions include vasodilation and smooth muscle relaxation. While BNP testing cannot replace a full assessment, it is a useful addition to diagnostic testing, in particular, to rule out heart failure in patients with symptoms such as breathlessness.
Can biochemical testing of oxytocin levels be used to monitor cardiovascular health?
Oxytocin is a hormone that has various functions mainly related to fertility, such as the development of gonads and promoting romantic and parental behaviors, but studies have also noted that oxytocin also affects cardiometabolic function and is involved in stress-related disorders. Due to this, there is interest in developing a biochemical test to measure levels of oxytocin.
Various testing methods have been applied, but the most common are immunoassays; this group of biochemical tests includes enzyme-linked immunosorbent assays (ELISA). These tests have been performed on various starting materials, including serum, plasma, and saliva. However, currently, these are not fully validated and there are no standards available for these tests to become routine clinical biochemistry testing.
Testing apolipoproteins to determine cardiac risk
Apolipoproteins are an important part of lipoprotein metabolism, and they also act as templates for lipoprotein synthesis as well as aiding the maintenance of lipoprotein structure. Lipoproteins are involved in transporting triglycerides to different organs, maintaining extracellular cholesterol levels, and reverse cholesterol transport.
Abnormal lipoprotein metabolism has been linked to atherogenesis, obesity, insulin resistance, and diabetes. As such, studies have investigated whether testing for lipoproteins and apolipoproteins can be used to determine dyslipidemia and cardiovascular risk.
Two apolipoproteins, apolipoprotein A (apoA) and apolipoprotein B (apoB) are associated with cardiovascular risk; apoA is inversely linked, while apoB is positively linked to cardiovascular risk. Therefore, a biochemical test that looks at the levels or ratios of these apolipoproteins has the potential to be used to determine cardiovascular risk.
Various studies investigated this potential and found that testing for apoB or apoA levels, or their ratio, could be a better marker for cardiovascular risk than other markers such as total cholesterol. This includes one study on 175,553 individuals who were followed for 65 months which showed an increase in relative risk of fatal myocardial infarction with an increase in apoB concentration.
Another study involving around 27,000 participants showed that an increase in the ratio of apoA and apoB was linked to myocardial infarction.
Yang, Z. and Zhou, D. M. (2006) Cardiac markers and their point-of-care testing for diagnosis of acute myocardial infarction Clinical Biochemistry https://doi.org/10.1016/j.clinbiochem.2006.05.011
Xu, L-Q. et al. (2018) Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies Heart, Lung and Circulation https://doi.org/10.1016/j.hlc.2017.03.165
bhf.org.uk Heart Failure
Cowie, M. R. et al. (2003) Clinical applications of B-type natriuretic peptide (BNP) testing European Heart Journal https://doi.org/10.1016/S0195-668X(03)00476-7
Gruson, D. (2018) Oxytocin testing and reproductive health: Status and clinical applications Clinical Biochemistry https://doi.org/10.1016/j.clinbiochem.2018.10.016
Dominiczak, M. H. and Caslake, M. J. (2011) Apolipoproteins: metabolic role and clinical biochemistry applications Annals of Clinical Biochemistry: International Journal of Laboratory Medicine https://doi.org/10.1258/acb.2011.011111