Saturday, May 6, 2017
Cardiac protein as an early predictor of heart attack
Very late last night just as I was already retiring to bed at nearly 3 am, I received a WhatsApp message from Professor Dr Andrew Charles Gomez, a very prominent and famous ENT Specialist asking my opinion of a claim by a speaker at a conference on nutrition and aging he attended who said that a heart protein called cardiac myosin can be used as early detector of heart attack?
I instantly got up from my bed to type my personal opinion on this to Prof Gomez
Dear Prof Dr Andrew Gomez,
I am surprised you heard from one of the conference speakers on nutrition and anti-aging you attended that cardiac myosin is used as an early detection of heart attack?
Since I was not at the conference, I do not have the details of that claim. This is the first time I heard of using cardiac myosin as an early predictor of AMI (acute myocardial infraction).
As you are a reputable medical specialist yourself, let us argue this logically.
First of all, myosin is not something new to scientists. Even during my student days in the early 1960’s we already learn about this protein both in our physiology, and later in our nutrition lectures, that this protein (myosin) is present in all muscles for their contractile functions.
There are essentially two types of myosin expressed by three different types of genes; two for skeletal muscles – namely, one for slow skeletal muscles, and the other for fast muscles; both of which are actually responsible for the conversion of energy-rich phosphate bonds ATP (adenosine triphosphate) into ADP (adenosine diphosphate) with the release of energy like muscle contraction. We all know that even in biochemistry.
The remaining 3rd type of gene (MYBPC3) exclusively expresses cardiac myosin that is responsible for the continuous non-stop contraction of the heart.
This protein (cardiac myosin) remains in the cardiac muscles at stable and low levels. But they may increase by drugs such as cardiac myosin activators in the event of a heart failure.
But I have never heard of a heightened expression of this cardiac protein even BEFORE an acute cardiac event such as AMI. This does not seem scientifically logical to me. How do you expect a gene able to know or predict that an acute event is going to happen that requires it to increase its (protein) expression? This is like fortune-telling and putting a cart before a horse.
In medicine, doctors ought to know (unfortunate a lot don’t) that in most diseases, biochemical lesions starts to appear in the blood before the clinical presentations become apparent. But this can only happen if the pathology is already present without the clinical features manifesting themselves in the early stages of the disease.
Just to give you one or two examples will do - hydroxyproline and hydroxylysine for collagen formation is low before gingival lesions become apparent in scurvy.
Another example is erythrocyte transketolase activity in the RBC is affected even BEFORE a thiamine deficiency and beri-beri clinically manifest itself.
Yet another simple example is blood sugar levels is elevated for months or years before polyuria, polydipsia, polyphagia, weight loss, retinopathy, nephropathy and other complications are presented as complications in diabetic patients.
Another example is the elevation of various liver enzymes - alanine transaminase, aspartate aminotransferase (SGOT)… etc., even before signs and symptoms of liver diseases are apparent.
There are hundreds more such examples of biochemical and protein expressions appearing BEFORE a clinical presentation following the existence of already an active pathophysiology
However there are also a number of examples where the biochemical expressions are not sensitive enough for them to appear first before the clinical lesions manifest themselves.
One example are the tumor markers for cancer detection. These markers are neither specific nor sensitive enough to detect a lurking cancer already in existence in the body until the neoplasm are already very massive and in an advanced stage.
The reason is probably an existing malignant tumour requires billion of cancer cells to collectively express sufficient amounts of abnormal malignant proteins to be sensitive enough for chemical detection.
In the event of tiny amounts of cellular cancers lurking in the body all the time which we all have, but dealt with by the immune system, these small amounts of malignant cells cannot express sufficient amounts of abnormal proteins for chemical detection.
The only exception I can think of are the prostate-specific antigen (PSA) where its blood elevation is common for both prostate cancer and benign prostatic hyperplasia (BPH). The only choice for diagnostic differentiation between PSA in prostate cancer and BPH is to look at the velocity of the PSA increase over time, and also the free and combined PSA ratios.
In a total PSA level, there will be more free PSA in BPH than in the case prostate cancer. That ratio expressed should be taken into consideration short of performing a TRUS biopsy (transrectal ultrasound biopsy) for differential diagnosis.
PSA detection expressed by the prostate gland is quite specific for prostate anomaly. The rest of the other tumor markers are neither sensitive nor specific. This is the only example I can think of at the moment as I type this sentence.
In short, in most cases biochemical changes precede a clinical presentation. It is the presence of an asymptomatic pathophysiology preceding that causes protein expressions as changes in the blood chemistry.
This is because the pathology is already actively present as a trigger factor for the genes to express the specific proteins. This is so logical to understand.
However, there is only one exception I can think of at the moment in which an acute event comes first; after which then there is an expression of a protein (enzyme).
In this exceptional example, there is an increase in cardiac enzymes creatine kinase (CK-MB), and also the troponin levels which are released by the heart muscle within 3-12 hours of onset of chest pain, reach peak values within 24 hours, and return to baseline after 48-72 hours.
These cardiac enzymes are released only after an AMI. This is because the heart muscles already suffered a damage, and the enzymes expressed are only an after effect. But there is no way the heart knows when it is going to suffer a sudden coronary insufficiency for it to express the enzymes beforehand?
So the genes responsible for such enzyme (protein) release can express themselves only after a sudden acute event. AMI happens when the coronary vessels suffers a sudden ischemic episode, unlike chronic diseases. In an AMI there is no way of predicting this instant event. This is logical.
So, how can cardiac myosin be expressed beforehand and detected as an early predictor before the heart even knows of an imminent sudden cardiac event? This beats my all my basic understanding in medical sciences
As we can clearly see from the example of CK-MB and troponin being released ONLY after the cardiac event has happened, I see no way can the gene MYBPC3 ability to express the myosin-binding protein C (cardiac myosin) before the event?
In lighter vein, genes are not fortune-tellers or harbingers that can foretell a medical catastrophe yet to come for person to take the necessary precaution.
What you heard from the conference presenter on nutrition and aging does not make scientific sense to me to the best of my understanding.
Maybe I need to get hold of his published paper (if any) to read the study, the methodology, data and inference.
Thank you for asking
Lim ju boo