(In the memory of my father, a common man, but a poet)
Heart attack that medically known as Myocardial Infarction (MI) is the leading cause of death in the developed countries and the second in the developing world with over 12% of the cause of the death worldwide. The prevalence of such deaths due to heart failure after acute myocardial infarction from the 10% within 30 days and 20% in 5 years in the 70’s, have skyrocketed to 23% and 34%, respectively, in the 90’s. MI usually is a result of Coronary Artery Disease (CAD) of the blood supplies to the heart muscles, that is caused by the occlusion of these arteries by atherosclerotic or lipid plaques that finally rupture and leading to the necrosis or infarction of the cardiac muscles, impeding its pumping function, finally failure and death.
The accumulation of the atherosclerotic plaques which is a long or chronic process, after years warns the individual with symptoms of Angina, e.g. chest pain that my feel like heartburn, radiating to left arm, shoulder and other associated symptoms such as nausea and vomiting, shortness of breath, numbness on the left side, faint feeling and cold sweat, etc. While the precipitating process is long, the end result could be sudden and acute, causing sudden death in minutes even at times without warning or chest pain, so called silent MI or heart attack. In certain situations, MI could happen without a precipitating long process, by coronary arteries spasm due to the use of some illicit drugs such as cocaine and extreme cold among others. (1-2)
Why a beating heart stops?
A beating heart does not stop incessantly, as it looks in the heart attack or myocardial infarction to be sudden and acute. Underlying a stopping heart or attack that is seemingly acute and sudden, there are chronic or long-standing processes that lead to its standstill. There are more than one factor in the process that ends in the heart attack and understanding of these factors could help to prevent sudden death from heart attacks. Although there are many modern treatment modalities from angioplasty to coronary bypass, saving an infarcted or a partially or more complicated dead heart muscle, hence saving lives, the ultimate goal in this arena needs to be prevention of such fatal accidents, as there are many unfortunate instances such as my father’s that any treatment even advanced ones could be already too late!
While to many people, including the patients themselves and their clinicians, heart attack or myocardial infarction is interpreted as coronary arteries (blood supplies to heart itself) occlusion, there is a big and long-standing secret behind it. Moreover the great majority of myocardial infarctions are not fatal, whether treated or untreated, and understanding, prevention and treatment of the precipitating factors are crucial as subsequent attacks may kill the person if not the first one, like in the case of my father. Among many of these factors, there are comorbidities or other illnesses such as diabetes mellitus or hypertension, plus the size and location of the infarct that influence the clinical course, treatment and prevention. The exact anatomic territory infarcted and whether it includes the sinus node or AV node or important neuro-receptors; whether many small arteries are occluded (especially downstream of narrowed main coronary branches) are all important. Also whether the heart is hypertrophied, dilated, infected, or infiltrated; and whether there may be intra-cardiac, extra-cardiac, or intracranial neuro-pathological conditions that could destabilize cardiac electrical activity are needed to be identified. (3)
Moreover it is known that apoptosis plays a major role in myocardial infarction or ischemia, but it also occurs within the heart completely and independently of infarction. There is also the vexing dilemma that an effective coronary collateral circulation, which is determined primarily by trans-anastomotic pressure gradient, is made less effective by exactly those treatments that reestablish flow in an occluded coronary artery. Since thrombolysis and angioplasty are automatically considered urgent treatment for an occluded coronary artery, it is prudent to remember the complex causes that determine whether the patient lives or dies. (3)
Moreover heart muscles or cardiomyocytes unlike many other body muscle cells, postnatally are withdrawn from the cell cycle and therefore the human heart has a very low capacity to regenerate after myocardial injury or MI. Shortly after acute myocardial infarction, neutrophils and monocytes invade the post-ischemic myocardium, remove the dead cells, then the anti-inflammatory cytokines released to stop the inflammatory process and causing fibroblastic scar formation. If the person survives an MI, the above inflammatory processes could cause further degradation of cardiac muscle cells, leading to further infarct expansion, left ventricular dilatation, aneurysm formation or even ventricular rupture. This is also well observed and supported by the increase in neutrophils, monocytes and macrophages in the coronary arteries endothelial muscle wall and even in the peripheral blood after infarct and such remodelling of left ventricular muscle, ultimately if not treated leading to heart failure and the individual survived from the acute MI and sudden death, to a gradual death!(4)
Atherosclerosis, which is the narrowing and occlusion of coronary arteries, supplying the blood to the heart, and is still considered the major cause of myocardial infarction is in fact an end stage in a long pathophysiologic process. This involves genetic and environmental risk factors, acting on their own or in synergy. Within the general population, polymorphisms within genes in lipid metabolism, inflammation, and thrombogenesis are probably responsible for the formation of atherosclerosis, leading in turn to the fatal outcome of myocardial infarction. Approximately 40 quantitative trait loci through genome-wide association search have been found in humans to be linked to atherosclerosis-susceptibility polymorphisms. Such discovery has paved the path to unveil the molecular basis of atherosclerosis and facilitate the discovery of drug targets and individualized medication treatments against this fatal disease. (5)
Long time before the Attack:
Long before the heart attack or myocardial infarction, there has been a process of the narrowing of coronary arteries supplying the heart, through accumulation of deposits of lipid or particularly bad cholesterol or LDL (Low Density Lipoprotein) leading to the sclerosis or atherosclerosis of these arteries. This is not the case with the good cholesterol or HDL (High Density Lipoprotein) or Triglyceride that do not esterify like LDL. (6-7) In addition to the obvious over-intake of lipids, specially cholesterol in the causation of atherosclerosis, there is a genetic susceptibility in accumulation of B-lipoprotein leading to such pathology in the arterial walls as for example alpha-proteins that are predominant in the young heart of newborns could not accumulate and lead to atherosclerosis.(8)
The family history or the genetic susceptibility of Coronary Heart Disease (CHD), independently of the established risk factors, such as lipid over-intake and obesity, is well known as different ethnic groups differ in the prevalence and incidence of CHD and protein-enzymatic markers. Genetic disorders of lipoprotein metabolism and transport, such as familial hypercholesterolemia, as well as apoprotein E polymorphism in determining plasma LDL variability among individuals are inherent underlying risk factors. (9)
One of the major consequences of cholesterol accumulation in the artery wall is thought to be the impairment of endothelial function. The endothelium is more than a physical barrier between the bloodstream and the artery wall. Under normal conditions, the endothelium is capable of modulating vascular tone, thrombogenicity, platelet function, and inflammation. In the presence of traditional risk factors, particularly dyslipidemias, these protective endothelial functions are reduced or lost. The encroachment ofthe atherosclerotic plaque mass on the vessel lumen and damage to the endothelium of the arterial wall, then obstruct the coronary blood flow, causing angina. Alternatively, cracks or fissures caused by irregular shaped atherosclerotic plaques may cause the arterial thromboses that in turn lead to angina and finally myocardial infarction. (10)
In the normal human heart, coronary collateral vessels are small and have no intervening capillary bed, between different coronary arteries or between branches of the same artery. But in patients with CAD, well-developed coronary collateral vessels may play a critical role in preventing death and myocardial infarction. Individual differences in the capability of developing a sufficient collateral circulation is a determinant of the vulnerability of the myocardium to coronary occlusive disease. It has been estimated that, in humans, perfusion via collateral vessels can equal perfusion via a vessel with a 90% diameter obstruction. Although coronary collateral flow can be sufficient to preserve structure and resting myocardial function, muscle dependent on collateral flow usually becomes ischemic when oxygen demand rises above resting levels. (11)
The last mystery is that why atherosclerotic plaque formation by lipoproteins accumulate mainly in the coronary arteries, causing CAD and in turn myocardial infarction or heart attack, and not in other body arteries. The main reason is that there is more to-and-fro blood flow in the coronary arteries, though there are as well as in the legs and the carotid arteries, two other regions more prone to blockages. This turbulent blood flow hurts the lining of arteries, much like heavy winds blowing back and forth over time can take a toll on the trees in a forest. Where blood flow resembles a gentle breeze in one direction, as in your arms, blockages are less likely to occur. (12)
As one reads in many articles on this site, majority of the human disease are caused by one or more types of insults to our being, either as microbial invasions, or physical, physiological, chemical or mental stress. In the case of heart attack or myocardial infarction, the insult is physiological/chemical by over-intake of fats or lipids, particularly cholesterol. Of course this while is the principal precipitating risk factor, the genetic, racial, gender and age susceptibility, and the rate of metabolism to burn the lipids are the other determining factors. Moreover the existence of other comorbid conditions or in a better word the general well-being of the individual is another vital determinant. Lastly the level of the activity of the person in burning the calories or lipids is another important lowering risk factor.
As detailed above and elsewhere, the accumulation of lipoproteins, particularly LDL in the blood circulation, ends gradually over years to deposits in the endothelial layers of the arterial lumens, specially the small and highly trafficked, kinked and bent ones, such as coronary arteries. This in turn leads to atherosclerosis or sclerotic lipid plaque formations in the arterial lumen and endothelium, narrowing or occluding the arteries. Hence the blood or oxygen supply to the heart is lowered and that leads to the ischemia, infarction or death of the heart or cardiac muscle, affecting the heart function, principally as a pump.
While all the above process is long and mostly masked and undetected with almost no symptoms for long, when the blood supply to the heart is compromised principally, the first symptoms would be of Angina, such as chest pain, shortness of breath and exertion difficulty. This first clinical sign will warn the patients and the clinicians, leading to treatments such as angioplasty and coronary bypass, all to rejuvenate the blood supply to the heart. While this is life saving in many cases, if the cardiac muscles in part or more is ischemic or dead, or the heart is already in a stage of hypertrophy or failure, the life will be still in danger. Therefore like many other human illnesses, the prevention is the key and should be the target, to not just save lives, but comorbidities, quality of life, and the cost that our capitalist system cares the most about!
Dr.Mostafa Showraki, MD, FRCPC
Lecturer, School of Medicine, University of Toronto
Author: ADHD: Revisited Book, Amazon Kindle Books
- Rischpler C. Acute myocardial infarction. Q J Nucl Med Mol Imaging. 2016 Sep;60(3):236-51.
- World Health Organization (2008). The Global Burden of Disease: 2004 Update. Geneva: World Health Organization.
- James TN. Complex causes of fatal myocardial infarction. Circulation. 1997 Sep 2;96(5):1696-700.
- Frangogiannis NG. The extracellular matrix in myocardial injury, repair, and remodeling. J Clin Invest. 2017 May 1;127(5):1600-1612.
- Chen Y, Rollins J, Paigen B, Wang X. Genetic and genomic insights into the molecular basis of atherosclerosis. Cell Metab. 2007 Sep;6(3):164-79.
- Bowyer,D.E.,Howard,A.N.,Gresham,G.A.,Bates,D.,and Palmer, D. V. (1968). Aortic perfusion in experimental animals: a system for the study of lipid synthesis and accumulation. Progr. biochem. Pharmacol.,4,235-243.
- Adams CW. The pathogenesis of atherosclerosis. J Clin Pathol Suppl (Assoc Clin Pathol). 1973;5:38-42.
- Morton NE. Genetic markers in atherosclerosis: a review. J Med Genet. 1976 Apr;13(2):81-90.
- Goldbourt U, Neufeld HN. Genetic aspects of arteriosclerosis. Arteriosclerosis. 1986 Jul-Aug;6(4):357-77.
- VanderWalAC,BeckerAE,vanderLoosCM,etal:Siteofintimalruptureorerosionofthrombosed coronary atherosclerotic plaque is characterized by an in ammatory process irrespective of the dominant plaque morphology. Circulation 89:36, 1994.
- Konidala S, Gutterman DD: Coronary vasospasm and the regulation of coronary blood flow. Prog Cardiovasc Dis 46:349, 2004.