New Concepts in the Prevention and Treatment of Coronary Heart Disease

Review Article

Ann Nutr Disord & Ther. 2015; 2(3): 1027.

New Concepts in the Prevention and Treatment of Coronary Heart Disease

Mark C. Houston*

Department of Medicine, Vanderbilt University School of Medicine, Hypertension Institute and Vascular Biology, Saint Thomas Hospital, USA

*Corresponding author: Mark C. Houston, Department of Medicine, Vanderbilt University School of Medicine, Hypertension Institute and Vascular Biology, Saint Thomas Hospital, 4230 Harding Road, Suite 400, Nashville, TN 37205, USA

Received: July 15, 2015; Accepted: September 11, 2015; Published: September 21, 2015


We have reached a limit in our ability to reduce the incidence of Coronary Heart Disease (CHD) and Cardiovascular Disease (CVD) utilizing the traditional evaluation, prevention, and treatment strategies for the top 5 cardiovascular risk factors– hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. Statistics show that approximately 50% of patients continue to have CHD or Myocardial Infarction (MI) despite “normal” levels of these five risk factors as traditionally defined. A more logical and in depth understanding is required of these top five risk factors including the evaluation of 24 hour ambulatory blood pressure monitoring, advanced lipid profiles, dysglycemic parameters, visceral obesity with effects ofadipokines and of the three finite vascular endothelial responses which include inflammation, oxidative stress and immune vascular dysfunction to the infinite number of insults. Understanding translational cardiovascular medicine to correlate the CHD risk factors to the presence or absence of vascular injury and disease with non -invasive vascular testing will allow for early identification, prevention and treatment of CHD and CVD.

Keywords: Cardiovascular disease; Hypertension; Dyslipidemia; Inflammation; Oxidative stress; Immune vascular dysfunction


Cardiovascular medicine needs a complete functional and metabolic reevaluation related to diagnosis, prevention and integrative treatments. We have reached a limit in our ability to treat cardiovascular disease (CVD) appropriately [1]. The cardiovascular system is literarily “on fire” Our present treatments are not effective in reducing this vascular inflammation.CVDremains the number one cause of morbidity and mortality in the United States [2]. Statistics show that we spend approximately $80 billion a yeartreating CVD alone [2] and over 2200 US citizens die fromstroke or MI each day [2-5]. CHD includes angina, MI, ischemic heart disease, ischemic cardiomyopathy with both systolic (low ejection fraction) and diastolic congestive heart failure (normal ejection fraction with stiff and non- compliant left ventricle.. The most common cause of CHF in the US is ischemic heart disease.

The traditional evaluation, prevention, and treatment strategies for the top 5 cardiovascular risk factors– hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking, have resulted in what is now referred to as a “CHD gap” [4]. Approximately 50% of patients continue to have CHD or MI despite having “normal” levels of these risk factors as currently defined in the medical literature [2,5]. We maintaina cholesterol-centric approach to the management of CHD but do not address the basic etiologies of CHD such as inflammation, oxidative stress and immune vascular dysfunction.. However, there are important details within each of these top 5 risk factors that are not being measured by physicians and are thus ignored in the prevention and treatment of CHD [2]. In fact, there are at least 395 other risk factors that physicians’ either do not know about or they are not using appropriate techniques to identify and treat them.

Thus, it is imperative that we now begin to examine other methods to prevent and treat CVD[2].

Revolutionizing the Treatment of Cardiovascular Disease

The blood vessel has three finite responses to an infinite number of insults [2]. Those responses are inflammation, oxidative stress, and vascular immune dysfunction. Tracking backwards from those 3 finite responses brings us to the genesis of CVD with the goal of starting effective treatments to resolve the downstream abnormalities,

Cell membrane physiology and cell membrane dysfunction are keys to this treatment strategy. This membrane barrier between the outside and the inside of every one of our cells such as the endothelium, enterocyte, theblood brain barrier, or any other membrane, determines all of the signaling mechanisms that occur from the external to the internal milieu [2].

Any cell membrane insult such as high blood pressure, LDL cholesterol, glucose, microbes, toxins, heavy metals or homocysteine results in a reaction diffusion wave throughout the cell membrane that disrupts the signaling mechanisms and induces membrane damage and dysfunction [6,7]. One small insult becomes a heightened response (metabolic memory) to create further cell damage [6,7]. The blood vessel is really an innocent bystander in a correct but often dysregulated vascular response to these infinite insults.

In the acute setting, any vascular insult results in a correct defensive response by the endothelium. The vascular immune dysfunction, oxidative stress or inflammatory responses are usually short-lived, appropriate, and regulated [2]. However, chronic insults result in a chronic exaggerated and dysregulated vascular dysfunction with preclinical then clinical CVD due to maladaptation of various systems such as the. Renin-Angiotensin-Aldosterone (RAAS) system, Sympathetic Nervous System (SNS) and others [2].

Most diseases are arbitrarily defined with a specific abnormal level. Hypertension is defined as greater than 140/90 mmHg, dyslipidemia as an LDL-cholesterol is over 100 mg/dL, and glucose intolerance as a fasting glucose over 99 mg/dL. [2] However, it is very clear that there exists a continuum of risk starting at lower levels of BP, LDL cholesterol and glucose as well as for most other CHD risk factors [2]. For example, we know that the blood pressure risk for CVD actually starts at 110/70 mmHg, and that the risk for LDL-cholesterol causing reduction in nitric oxide in the endothelium starts at 60 mg/dL and fasting glucose risk starts at 75mg/dL [2]. There is a progressive continuum of risk with all of the CVD risk factors and mediators that effect the blood vessel, leading initially to functional abnormalities (endothelial dysfunction), then to structural abnormalities of the vascular and cardiac muscle and topreclinical and clinical CVD.

Finally, it is important to understand the concept of“translational vascular medicine.” For example: Do the risk factors that are measured actually translate into a vascular illness? And, vice versa: Does the absence of those risk factors actually define vascular health? At this time we often do not use functional and structural markers of vascular and endothelial dysfunction to identify the vascular effects of CHD risk factors or the presence of vascular disease. Instead, we are relying only upon risk factors or some risk factor scoring system such as Framingham or COSEHC (Consortium of Southeastern Hypertension Centers). We assume that if a patient has risk factors, they also have vascular disease; but if they don’t, they may have vascular health. It is important to measure sensitive indicators of endothelial dysfunction and vascular structural disease that are induced by the insults. Early detection with aggressive treatment will reduce CVD.

The Endothelium, Endothelial Function, and Endothelial Dysfunction

The endothelium is a very thin lining of vascular cells which forms an interface between the circulating blood in the lumen and the vascular smooth muscle [2,4,8]. When the endothelium is working correctly (endothelial function) all the blood elements and the vascular smooth muscle remain normal. However, when endothelial dysfunction occurs, the results are inflammation, oxidative stress, immune dysfunction, abnormal growth, vasoconstriction, increased permeability, thrombosis andultimately CVD [2,4,8,9s].

Figure 1 illustrates LDL-cholesterol’s role in atherosclerotic plaque formation [10]. Once inside the vessel wall LDL-cholesterol becomes susceptible to oxidation and modification by free radicals and glycation [10]. Oxidized-LDL and glycated LDL are toxic to the vessel wall. The modified LDL is consumed by scavenger receptors (SR-A and CD-36) on macrophages to form foam cells. Foam cells are not able to process the oxidized-LDL or modified LDL and continue to accumulate oxidized and modified-LDL forming a plaque which may rupture and cause acute coronary thrombosis.This is the progression that needs to interrupted. There are actually 38 different steps in this process that are important in the treatment of dyslipidemia- induced vascular disease [10].