March 2017

Suggested Citation: Garko, M.G. (2017, March). Coronary heart disease – Part II: The pathogenesis of the leading cause of death in the United States. Health and Wellness Monthly. Retrieved (insert month, day, year), from

Coronary Heart Disease – Part II: Pathogenesis of the

Leading Cause of Death in the United States

Michael Garko, Ph.D.

Nationally Syndicated Host & Producer – Let’s Talk Nutrition



Although there is an ongoing scientific debate about what triggers it, there is little debate among medical investigators that atherosclerotic inflammation is the underlying cause of coronary heart disease (CHD).[1] Just as it is the responsibility of health consumers to monitor the condition their hearts, it is their responsibility to understand the role of inflammation in the pathogenesis of CHD and to learn about the various inflammation promoting risk factors associated with CHD, a topic which will be explored in an upcoming issue of Health and Wellness Monthly.

Understanding the underlying disease process of CHD is crucial to grasping what it is, how it comes about and its health consequences (i.e., death or disability). Moreover, knowing about the cause, disease development and effects (i.e., pathogenesis) of CHD provides insight into how best to prevent or reverse it or otherwise maintain long term cardiovascular health.

The March, 2017, issue of Health & Wellness Monthly is an update of an article focusing on the pathogenesis of CHD.

Pathogenesis of CHD: Atherosclerosis and Inflammation

Coronary heart disease (CHD) is a disease of the heart in which the inner endothelial lining or walls of one or more of its coronary arteries[2]  become partially or completely narrowed by a long-term accumulation of atheromatous plaque[3]  CHD is a direct consequence of atherosclerosis, an inflammatory disease process involving the gradual accumulation of plaque taking the form of lipid laden lesions (atheromas) on the inner walls of the coronary arteries[4]. Atherosclerosis begins in early childhood (before age 10) with the appearance of soft, fatty streaks along the inner walls of the coronary arteries (McGill et. al, 2000)[5]. They do not block the flow of blood in the early stages of their development. However, over an extended period of time these fatty streaks evolve into thickened and hardened fibrous plaques/lesions. The atheromatous plaque builds up narrowing (i.e., stenosis) the open space (i.e., the lumen) within the arteries and preventing blood to flow freely.

One of the consequences of plaque narrowing the lumen is that the heart cannot receive a sufficient supply of fresh oxygenated blood, weakening the structure and function of the heart muscle. Another consequence is that the hard, fibrous outer shell of the plaque can rupture. When this happens platelets form a blood clot around the lesion. The clot can then block the flow of oxygenated blood through the already obstructed artery. If the artery becomes blocked completely, then within a short period of time the heart becomes starved for oxygen (ischemia) and the heart muscle cells begin to die resulting in permanent damage. This is medically termed a myocardial infarction. In common parlance, it is called a heart attack.

Typically, red blood cells, low-density lipoproteins (LDL), high-density lipoproteins (HDL), monocytes, and platelets course easily through healthy coronary arteries. However, when damage is done to the endothelial cells lining the arteries the immune system’s inflammation response is triggered to repair the damage.

What sets the inflammation response into motion is debated vigorously in the literature. Among other factors, viruses, bacteria, excessive, oxidized LDL cholesterol, hypertension/high blood pressure, homocysteine, tobacco smoke toxins, industrial chemical toxins, alcohol, refined sugar, excess saturated and trans-fats, insulin, excess refined, processed carbohydrates have all been mentioned as causes of inflammation or at least risk factors for it.  The debate about what causes atherosclerotic inflammation will not be settled in this article

Nevertheless, one plausible explanation derived from various scientific studies involves the oxidation of lipids (in particular LDL cholesterol) or what is termed as the lipid peroxidation hypothesis. It is hypothesized that when one or another inflammatory agent(s) damage(s) the endothelium lining of the coronary arteries the immune system kicks in and sends white blood cells to repair the injured site. Because it is a large-sized transporter of cholesterol, the LDL becomes trapped in the inner most layer of the arterial wall called the intima, which consists of a continuous layer of endothelial cells. Some of the trapped LDL then becomes oxidized by free radicals producing an inflammation response.

As the LDL is oxidized within the intima, monocytes flood to the inflamed site to then become macrophages. The macrophages literally consume the now oxidized LDL and grow into foam cells, which in turn become oxidized, thereby, promoting even more inflammation and immune scavenging macrophages to try and undo the cellular damage done to the endothelium. In the attempt to repair the oxidative damage, there is a proliferation of smooth muscle cells lining the arterial wall. The smooth muscle cells and macrophages produce connective tissue, all of which becomes mixed with the foam cells resulting in the scar-like tissue of fibro-lipid plaque to form along the arterial wall. Mineralization takes place further hardening the plaques and advancing the disease. This process repeats itself resulting in multiple layers and larger areas of plaque developing in the coronary arteries (e.g., see Berliner et al., 1995; Heinecke, 1998; Navab, et al., 1996; Raines et al., 1996; Ross, 1992, 1999; Witztum & Steinberg, 1991).


Notwithstanding the debate about what triggers inflammation in the coronary arteries, there is considerable theoretical and empirical support for viewing atherosclerosis as an inflammation disease. Research has revealed that immune implicated substances such as cytokines, T-lymphocytes, leukocytes, fibrinogen, Interlukin-1b, Interlukin-6, C-Reactive Protein (CRP), Macrophage-Monocyte Colony Stimulating Factor (MCSF) are associated with atherosclerosis (e.g., see Andreotti et al., 1999; Bauer et al., 1988; Cermak et al., 1993; Danesh et al., 1998; Dinarello, 1993; Libby & Ross, 1996; Luster, 1998; Rajavashisth et al., 1990; Ross, 1992, 1999; Shyy et al., 1993; Sironi et al., 1989); this research provides further evidence that atherosclerosis is an inflammation disease. Hence, if atherosclerosis is the underlying disease process of CHD and is inflammation based, then this suggests that the origination and development of CHD is connected to an immune or autoimmune response to injured endothelium by inflammation triggering agents.


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Suggested Citation: Garko, M.G. (2017, March). Coronary heart disease – Part II: The pathogenesis of the leading cause of death in the United States. Health and Wellness Monthly. Retrieved (insert month, day, year), from


[1] CHD is variously referred to in the literature as coronary artery disease (CAD), atherosclerotic heart disease and ischemic heart disease. At the same time, some writers even make a distinction between CHD and CAD. The terminological and definitional inconsistencies in the literature on CHD have contributed to the conceptual confusion confronting health consumers on cardiovascular disease (CVD), generally, and CHD, specifically.


[2] The arteries that supply oxygenated blood to the heart are termed “coronary” because they surround the heart in the form of a crown.

[3] Atheromatous plaque is made-up of such substances as cholesterol, proteins, calcium, fibrin, foam cells, smooth muscle cells and other elements. Structurally, atheromatous plaque can be divided into three distinguishable parts. There is the 1.atheroma (a mound or nodule of accumulated soft, flaky, yellowish material) occupying the center of larger plaques, 2. an underlying area of cholesterol crystals, and 3. calcification located at the outer area of more advanced lesions (Wikipedia, 2006).