The cluster of cardiovascular diseases that make up the metabolic syndrome

Jonathan Barnicoat, Marra Murphy, Vanita Patel & Igor Pushkarsky

Introduction

Atherosclerosis

Coronary heart disease

Peripheral arterial disease

Stroke References

Aortic disease

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Aortic disease risk factors alone are not enough to explain its prevalence in patients who also have metabolic syndrome. The link is explained with a similar imbalance of MMP/TIMP molecules. (Chavey, C 2003)One of the most common types of aortic diseases is an aortic aneurysm (AAA).

Figure 2: (John Hopkins, 2014)

Mechanism:• Plaque formation causes partial vessel occlusion• Calcification of the medial layer leading to loss of elasticity and structural

weakness• Destruction of the aortic media through degradation of elastin and

collagen, leads to weakening in strength of the aortic wall. • MMP9 has shown elastolytic properties and shows a critical role in AAA

formation• MMP9 is found at higher levels in larger aneurysms.• Nitric oxide induces MMP9 expression. (Fortuño, A 2005)

Figure 3: (Chavey,C 2003)

An atherosclerotic plaque is the cause of coronary heart disease, peripheral arterial disease and the most common form of strokes. It is a disease process that obstructs blood flow by the formation of plaques that causes hardening of the blood vessels. The process of atherosclerosis begins with damage to the endothelium, which can be caused by hypertension, high LDL blood cholesterol and smoking (Fox, S. 2008).

Figure 1: (Healthy Protocols, 2015)Once damage has occurred the elevated levels of LDL accumulate around the damaged site within the inner layer of the artery wall and they become oxidized. This causes substances to be released that attract monocytes from the blood that become converted to macrophages. These macrophages then ingest the excess LDL causing them to become foam cells. T lymophocyte cells are also attracted to the site of damage and secrete chemicals that increase the inflammation at the site. These combined actions form a fatty streak (Tortora, J. & Derrickson, B. 2011).

The Metabolic syndrome is a cluster of increased risk factors for cardiovascular diseases. Many criteria exist to diagnose a patient with metabolic syndrome, however the most accepted and up to date is the international diabetes foundation. Using their criteria to be diagnosed with metabolic syndrome the patient must have a waist circumference exceeding the ethnicity specific value as shown in table 1. They must also exceed two of the following four factors that can be seen in table 2.

Table 1: Waistline circumference Table 2: The other 4 factors that for different ethnicities that defines can be used to diagnose a patientcentral obesity. (International diabetes with metabolic syndrome. (International diabetes federation, 2006) federation, 2006)

A patient with metabolic syndrome has a greater elevated risk factor for developing cardiovascular diseases (CVD). A cardiovascular disease is a disease that affects either the heart or blood vessels. We have focused on four CVD’s these are aortic disease, coronary heart disease, peripheral arterial disease and stroke.

Abstract ConclusionPeripheral arterial disease (PAD) is a common circulatory problem in which narrowed arteries reduce the blood flow to limbs.The narrowing of arteries is a direct effect of MMP imbalance.When PAD affects arteries that supply blood to the heart it can cause angina and heart attacks, when it occurs in the neck or brain it can cause a stroke. (de Smet, B. J, 2000)

Figure 5:  (Chavey,C 2003)

Ischemic stroke occurs when the brain is deprived of oxygen due to a blood clot, leading to a reduced flow of blood. This causes sudden death of neurons and glial cells. Blood clots arise in areas where the arteries have been blocked or narrowed by fatty deposits called plaques by a process called atherosclerosis which is induced by the components of metabolic syndrome such as high blood pressure, obesity and high cholesterol levels.

Kurl et al. (2006) conducted a study in eastern Finland on the relationship of metabolic syndrome and the risk of stroke in middle-aged men results are shown in figure 6.         

Figure 6: Shows the cumulative risks for ischemic stroke in men with and without metabolic syndrome for an average follow up of 14.3 years (Kurt et al., 2006, P.809).

A similar study was conducted on women in Japan by Takahashi et al. (2007). The results collected are shown in figure 7.        

   

Another study conducted by Koren-Morag, Goldbourt and Tanne (2005) compared the relationship between metabolic syndrome and ischemic stroke in both men and woman; their results are shown in figure 8.

Coronary Heat Diseases (CHD) is caused by the accumulation of fatty deposits on the coronary arteries that surround the heart. The fatty deposits is knows as atheroma and is build up of:• Cholesterol• Fats • Excreted substances

Blood and oxygen supply to the heart decreases due to the fatty deposits blocking and narrowing the arteries, causing chest pain (angina) or a heart attack. (AHA 2014).

Metabolic syndrome increases the chance of developing coronary heart disease by a number of factors. Firstly, it causes endothelial dysfunction which is an imbalance produced substances on the endothelium, in terms of vasodilation and vasoconstriction. As well as increasing the thrombogenicity of circulating blood. (Alessi MC, 2008). Another influence the metabolic syndrome has on CHD is that it proliferates arterial stiffness (Wang, 2014)

Figure 4: John Hopkins (2014)

In Europe, CHD accounts for most deaths each year (almost two million, representing 21% of all mortality (Rayner & Petersen, 2000).

Being diagnosed with metabolic syndrome places patient at a 2 fold higher risk of developing a cardiovascular disease that can lead to morbidity or mortality. Coronary heart disease is the most prevalent of the four cardiovascular diseases(CVDs) mentioned and has the highest mortality rate of any disease in the UK.

Treatment for metabolic syndrome involves two key lifestyle changes. A healthier diet will help to lower blood cholesterol and triglycerides levels and regular exercise will decrease body fat and also lower blood pressure. Smoking is an inducing factor of the metabolic syndrome and all of the cardiovascular disease mentioned, therefore quitting greatly helps in the treatment of metabolic syndrome. Being diagnosed with metabolic syndrome does not in itself confer any form of pathophysiological disease development, it only demonstrates an increased risk of development of a cardiovascular disease or many other non cardiovascular disease such as type 2 diabetes.

Antihypertensive drugs and smoking cessation have been proven to have no effect on the condition in other studies. Therefore understanding precisely which molecules mediate CVDs development could lead to effective therapies. Most likely areas of success in understanding of CVDs are MMP/TIMP ratios in metabolic syndrome and their effect on vascular tissue (Chavey, C 2003) and effect of NO on the vascular structure and new selective NADPH oxidase inhibitors. (Dugic, E 2014)

Metabolic syndrome leads to a remodelling of the endothelial membrane in arteries which promotes leukocyte activation. As well as an increase in oxidative stress and alteration in matrix metalloproteinase proteinases (MMP) concentration. The effect of the previously described factors, surfaces through various cardiovascular diseases that appear in an increased frequency in people with metabolic syndrome as opposed to those that do not have the syndrome. In this poster we have outlined the pathophysiology of the most common diseases that are associated with metabolic syndrome, their risk factors and potential treatments.

Figure 7: Shows the cumulative risks for ischemic stroke for women with and without metabolic syndrome (Takahashi et al., 2007, P. 647).

Figure 8: Shows the incidence rates for men and woman per 100 person-years for ischemic stroke or TIA by the number of components that makeup metabolic syndrome (Koren-Morag et al., (2005), P. 1369).