Atherosclerosis: A Lethal Cardiovascular Killer

Suggested Citation: Garko, Michael (2018, November). Atherosclerosis: A Lethal Cardiovascular Killer. Retrieved from


Atherosclerosis: A Lethal Cardiovascular Killer

Dr. Michael Garko, Ph.D.

Host & Producer of Let’s Talk Nutrition


Atherosclerosis is a stealth-like, lethal, cardiovascular-related killer. Epidemiologically speaking, atherosclerosis (also called atherosclerotic cardiovascular disease [ACD]) is recognized as the leading cause of mortality and morbidity around the world, notwithstanding medical advances on how to prevent and treat it (Barquera et al., (2015; Fog et al., 2014; Ladich, 2016). Coronary heart disease (CHD), stroke and peripheral artery disease are recognized as the primary medical conditions associated with atherosclerosis, with CHD as the principal cause of death in the United States and worldwide (Barquera, 2015; Benjamin et al., 2018; Fog et al., 2014; Herrington, et al., 2015). CHD, the most frequently occurring cardiovascular consequence of atherosclerosis, takes the lives of over 370,000 victims annually in America (Mozaffarian et al., 2015). In terms of coronary events (e.g., myocardial infarction/heart attack & death) associated with CHD, approximately 635,000 people experience a first-time heart attack and 300,000 individuals suffer a recurrent heart attack annually. These startling statistics on the human toll associated with just CHD reveal what a threat ACD is to the health, wellness and life of people.

Etiology and Pathogenesis of Atherosclerosis

Atherosclerosis is an artery-occluding inflammatory disease (Libby et al., 2002; Ross, 1999). Currently, the exact etiology of atherosclerosis is illusive (National, Heart, Lung & Blood Institute, 2018). Nevertheless, a robust body of research describes and explains the various pathogenic stages or otherwise the atheromatous plaque forming process of atherosclerosis (Aziz & Yadav, 2016; Bhanvadia, 2013; Delewi, et al., 2013; Fog et al., 2013; Singh et al., 2003).

Steps of Atherogenesis[1]

It is important to point out that atherogenesis (i.e., process of forming atheromatous plaque in the coronary arteries) occurs within the environment of the endothelium, which lines the interior surface of arteries. While consisting of only a thin layer of cells, the endothelium serves as an important barrier between the blood circulating through the lumen of middle- and large-sized arteries (the targets of atherosclerosis) and the remainder of the arterial wall. It is the failure of this barrier function that sets in motion the inflammatory process of atherogenesis, and, hence, atherosclerosis (Delewi, et al., 2013).

Step 1- Presence of injurious agents. A necessary condition for the process of atherosclerosis to be initiated is the presence of an injurious agent (Delewi et al., 2013), possessing the potential to damage the endothelial lining of the arteries. Any number of such damaging agents have been identified in the literature (e.g., hypercholesterolemia, hypertension, hyperglycemia, trans- and saturated fats, tobacco smoke toxins, viruses, bacteria, homocysteine and alcohol) (Aziz & Yadav, 2016; Delewi, et al. 2013; Fog et al., 2014; Fruchart et al., 2004; Glasser, 1996; Vogel, 1997). The presence of these deleterious agents increases the endothelial production of ROS (reactive oxygen species), resulting in the endothelium becoming “inclined to exhibit proinflammatory processes, such as secreting inflammatory cytokines” (Delewi, et al., 2013, p. 23).

Step 2 – Breach in the endothelium. The pathological process of atherosclerosis is initiated when an injurious agent intrudes and damages the intact lining of the endothelium or otherwise creates a breach in the endothelial barrier, resulting in endothelial permeability and an atherosclerotic lesion (Delewi, et al. 2013). One of the hallmarks of atherosclerosis is a breached endothelium, which sets in motion endothelial dysfunction (Aziz & Yadav, 2016; Bhanvadia, 2013; Delewi, et al., 2013; Fog et al., 2013; Singh et al., 2003).

Step 3 – Oxidation, immune response and inflammation. With a breached endothelium, LDL cholesterol streams unimpeded into the Tunica Intima (TI), the first layer of the endothelium. Once inside the endothelium lining, the LDL cholesterol molecules begin to collect where they become oxidized, triggering an immune response, accompanying inflammation and oxidative stress (Aziz & Yadav, 2016; Delewi, et al. 2013; Fog et al., 2014; Fruchart et al., 2004; Glasser, 1996; Vogel, 1997). Specifically, as the LDL is oxidized within the TI, leukocyte recruitment is initiated, whereby, monocytes move into the injured endothelial site to repair it, inspiring inflammation (Berliner, J.A. et al., 1995; Delewi, et al., 2013; Shyy, et al., 1993; Witztum, 1991). Inflammation is another hallmark of atherosclerosis. In fact, inflammation is a defining feature of atherosclerosis to the extent that it is implicated throughout every stage of atherogenesis (Libby et al., 2002).

Step 4 – Formation of foam cells. The monocytes located within the TI consume the cholesterol and eventually become macrophages, which consume even more oxidized cholesterol. Over time, the gorged-filled macrophages die and become foam cells (dead macrophages). The foam cells in turn release cytokines and an out-and-out inflammatory response is mounted by the immune system. As foam cells build-up, they form a fatty streak that runs along the length of the damaged area of the inner lining of the endothelium. The process repeats itself until there is such a build-up of oxidized cholesterol, macrophages and foam cells that a bulge forms in the middle of the artery, obstructing the flow of blood through the arterial lumen (Aziz & Yadav, 2016; Bhanvadia et al., 2013; Delewi, 2013; Fog et al., 2014; Sing et al., 2002;).

Step 5 – Smooth muscles cells and formation of a fibrous cap. At this stage, because of inflammatory signals being sent out from the injured site, smooth muscle cells (SMCs) become involved in the pathogenic process with their proliferation, migration and movement into the fatty plaque collected in the TI. Once they flow into the TI, the SMCs secrete collagen and elastin that create a fibrous-protein cap, covering the potentially thrombus-producing fatty plaque. The fibrous prevents the plaque from coming in contact with the blood passing by the damaged area of the artery. In the meanwhile, more and more inflammation-producing oxidized cholesterol, gorging macrophages and inflammation-producing foam cells amass in the TI; this adds to the ever increasing amount of fibrous fatty-plaque that at this stage is most likely protruding into the lumen of artery. Of concern is the possible rupturing of the plaque’s fibrous outer cap. If it does rupture, platelets will form a blood clot around the fibrous cap, blocking the flow of blood through an already plaque-laden, obstructed artery (Aziz & Yadav, 2016; Bhanvadia et al., 2013; Delewi, 2013; Fog et al., 2014; Sing et al., 2002).

Step 6 – Smooth muscle cells and calcification. In addition to secreting collagen and elastin to form a fibrous cap over the lipid-laden plaque, the SMCs deposit calcium crystals into the fat-laden plaque in order to repair the oxidative damage done to the artery. This process of mineralizing the artery hardens the plaque, causing the arteries to become stiffer and, thereby, advancing the disease (Aziz & Yadav, 2016; Delewi, et al. 2013; Fog et al., 2014; Fruchart et al., 2004; Glasser, 1996; Vogel, 1997).

Risk Factors Associated With Atherosclerosis

Atherosclerosis is a complex, pathogenic, inflammatory disease of the arteries involving modifiable and nonmodifiable risk factors. The recognized modifiable risk factors include hypercholesterolemia, high blood pressure, cigarette smoking, high fat diet, physical inactivity, stress and diabetes, while the nonmodifiable risk factors include age, gender, ethnicity, aging, family history  (Glasser et al., 1996; Kronmal et al., 2007; Long et al., 2017; Ross, 1999; Singh et al., 2002; Vogel, 1997).

Assessment of Atherosclerosis

Methods of assessment related to atherosclerosis include the physical exam and a variety of clinical tests. Part of the physical exam for atherosclerosis often involves the physician placing a stethoscope over the patient’s arteries and listening “for an abnormal whooshing sound called a bruit … which may indicate poor blood flow due to plaque buildup” (National Heart, Lung Blood Institute, 2018, p. 1).

The Cleveland Clinic’s assessment protocol includes the following blood tests for atherosclerosis: Lipoprotein A, apolipoprotein A1, apolipoprotein B, peptide (NT-proBNP), Lp-PLA2, urine albumin/creatinine ratio, global risk score (Cleveland Clinic, 2018).

According to the Institutes of Health (2010) other diagnostic tests include: Angiogram, ankle/brachial index, computed tomography scan, carotid artery ultrasound, echocardiogram, electron beam computed tomography (EBCT), electrocardio gram, magnetic resonance imaging, PET scan (positron emission tomography), Fibrinogen, N-terminal-pro-B-type Natriuretic (Institutes of Health, 2010).

Interventions for Atherosclerosis

Interventions for atherosclerosis include medical procedures, surgery, medications, along with diet and lifestyle changes. The Institutes of Health (2010) recommends the following medical procedures and surgeries for atherosclerosis: Angioplasty, coronary artery bypass grafting, carotid endarterectomy, bypass grafting.

When diet and lifestyle modifications fail to reduce cholesterol (a major risk factor for atherosclerosis), the standard of traditional medical care includes prescribing statin drugs (e.g., Atorvastatin, Fluvastatin, Lovastatin, Pravastatin and Rosuvastatin), which serve the purpose of blocking the HMG-CoA reductase, an enzyme responsible for cholesterol production in the liver (Harvard Health, 2018).

In conjunction with the traditional medical approach involving the use of surgery and medications to treat atherosclerosis, it would be prudent to adopt a functional medicine approach focusing on diet, lifestyle and dietary supplementation. For example, although it is intended for patients suffering from high blood pressure, the DASH diet (i.e., Dietary Approaches to Stop Hypertension) is a proven eating plan for overall cardiovascular health and would benefit patients suffering from atherosclerosis (National Heart, Lung, and Blood Institute, 2018). The DASH eating plan is constituted primarily of whole foods, especially, vegetables, fruit, grains and grain products, low fat and non-fat dairy products, nuts, seeds and legumes, along with lean meats (e.g., poultry and fish, (National Heart, Lung, and Blood Institute, 2018). Another diet that has proven effective in preventing, treating and reversing atherosclerosis is a whole food plant-based diet, no meat, no dairy and no oil (see Esselstyn & Golubic, 2014; Esselstyn, Gendy, Doyle & Golubic, 2014).

Three important lifestyle changes that are necessary conditions to prevent and treat atherosclerosis are the elimination of tobacco products, stress management and regular physical exercise, especially cardiorespiratory/aerobic exercises (see American Heart Association, 2018; Lichtenstein, 2006; Pizzorno & Murray, 2013). In terms of regular physical exercise, the American Heart Association (AHA) recommends aerobic activities such as dancing, walking, running, cycling and swimming, along with an active engagement in such sports as tennis, basketball, soccer and racquetball (American Heart Association, 2018).

Finally, in the spirit and practice of a functional medicine approach to atherosclerosis, there is an array of clinically studied dietary supplements that can be used in conjunction with a heart healthy diet and a cardiovascular-related program of exercise.[2] The following is a list of clinically studied dietary supplements to help prevent, moderate and treat atherosclerosis: Aged-garlic extract, artichoke extract, berberine, butyrate, carnosine, curcumin, CoQ10, niacin/vitamin B3, omega3 fatty acids, fiber (soluble), lycopene, phytosterols (stanols & sterols), policosanol, red yeast rice, resveratrol and vitamin D  (see Moss & Ramji, 2016; Moss, Williams, & Ramji, 2018; Murray, 2013).


Atherosclerosis is a lethal, cardiovascular killer. With it being the primary pathogenic mechanism of action for CHD, stroke and peripheral artery disease, it is the leading cause mortality and morbidity worldwide. The six steps of atherogenesis described above reveal how susceptible the endothelium lining of the arteries is to being damaged by an array of injurious agents. While there are nonmodifiable risk factors associated with atherosclerosis, the modifiable risk factors of diet and lifestyle account for most of the variance for the arteries becoming diseased. Traditional and functional medicine interventions in combination can go a long way in preventing, moderating and treating atherosclerosis.


American Heart Association (2018). Endurance/aerobic exercise. Retrieved from

Aziz M, Yadav KS. (2016) Pathogenesis of Atherosclerosis. Medical & Clinical Reviews. 3(22) 2(3), 1-6.

Berliner, J.A. et al. (1995). Atherosclerosis: Basic mechanisms. Oxidation, inflammation, and genetics. Circulation, 91(9), 2488-2496.

Bhanvadia, V.M., Desai, N.J., & Agarwal, N.M. (2013, November). Study of Coronary Atherosclerosis by Modified American Heart Association Classification of Atherosclerosis-An Autopsy Study Journal of Clinical Diagnosis Res., 7(11), 2494–2497.

Cleveland Clinic (2018). Blood tests to determine risk of coronary artery disease. Retrieved from

Delewi, R., Yang, H. & Kastelein, J. (2013). Atherosclerosis. Textbook of Cardiology. Retrieved from

Glasser, S.P. Selwyn, A.P. & Ganz, P. (1996). Atherosclerosis: Risk factors and the vascular endothelium. American Heart Journal, 131 (2), 379-384.

Harvard Health (2018). Atherosclerosis. Retrieved from

Institutes of Health (2010). Coronary artery disease: Diagnosis and treatment. NIH Medline Plus, 5(3), 26 – 27.

Lichtenstein, A.HAppel, L.J., & Brands, M. et al. (2006). Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation, 114(1), 82-96

Mozaffarian D, Benjamin, E. J., Go, A.S. et al. (2015). Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation: 131, e29-322.

Murray, M. (2013). The textbook of natural medicine (4th ed.). J.E. Pizzorno (Ed.). London, England: Churchill Livingstone.

Moss, J.W.E. & Ramji, D.P. (2016, September). Nutraceutical therapies for atherosclerosis. National Review of Cardiology, 13(9), 513–532.

Moss, J.W.E., Williams, J.O. & Ramji, D.P. (2018, May). Nutraceuticals as therapeutic agents for atherosclerosis. Biochimica et Biophysica Acta Biochim Biophys Acta, 1864(5Part A), 1562–1572.

National, Heart, Lung & Blood Institute (2018). Atherosclerosis. Retrieved from

National Heart, Lung & Blood Institute (2018). DASH eating plan. Retrieved from

Punwani, V. (2014). Atherosclerosis. Retrieved from

Ross, R. (1992). The pathogenesis of atherosclerosis. In E. Braunwald (Ed.), Heart disease (pp. 1106-1124). Philadelphia: W. B. Saunders.

Ross, R. (1999). Atherosclerosis-an inflammatory disease. New England Journal of Medicine, 340, 115-126.

Singh, R.B., Mengi, S.A., Xu, Y.J., Arneja, A.S. & Dhalla, N.S. (2002). Pathogenesis of atherosclerosis: A multifactorial process. Experimental Clinical Cardiology, 7(1):40-53.

Witztum, J.L. (1991). The role of oxidizied low density lipoprotein in athrogenesis. Journal of Clinical Investigation, 88, 1785-1792.

Wolf, A. (2012a). Atherosclerosis: Part I. [Video File]. Retrieved from

Wolf, A. (2012b). Atherosclerosis: Part II. [Video File]. Retrieved from

[1] The discussion of the steps/stages of the pathogenesis of atherosclerosis presented in this essay is a composite and adaptation of different discussions and models of atherogenesis presented in the literature (e.g., Aziz & Yadav, 2016; Bhanvadia et al., 2013; Delewi, 2013; Fog et al., 2014; Punwani, 2014; Sing et al., 2002; Wolf, 2012a; Wolf, 2012b). Although they are videos, I am also giving attribution to Wolf (2012a & 2012b) and Punwani (2014), since they have greatly influenced my thinking about and understanding of the pathogenesis of atherosclerosis, which is reflected in the discussion on the steps of atherogenesis.

[2] Space limitations preclude a full discussion of the mentioned dietary supplements for atherosclerosis. Hence, the supplements are mentioned without a description of their mechanism of action in relation to atherosclerosis. However, the in-text citations provide an in-depth treatment of those clinically studied supplements known to help prevent and treat atherosclerosis.