atherosclerosis.pdf

Atherosclerosis Dr.Haidar H. Sallum Consultant physician  Definition The term atherosclerosis is derived from Greek “Athero”, meaning gruel or wax, corresponding to the necrotic core at the base of atherosclerotic plaque, and “sclerosis” for hardening or induration, refe...

Atherosclerosis Dr.Haidar H. Sallum Consultant physician  Definition The term atherosclerosis is derived from Greek “Athero”, meaning gruel or wax, corresponding to the necrotic core at the base of atherosclerotic plaque, and “sclerosis” for hardening or induration, referring to the fibrous cap of the plaque’s luminal edge.  Introduction Atherosclerosis is the most important underlying cause of : -Coronary artery disease (Angina , Myocardial infarction). -Cerebrovascular disease (Stroke). -Peripheral vascular disease. Coronary artery disease (CAD) is the most common cause of angina and acute coronary syndrome and the most common cause of death worldwide. The World Health Organization (WHO) has estimated that 3.8 million men and 3.4 million women die from cardiovascular disease (CVD) each year. 1 in 3 men and 1 in 4 women die from CAD An estimated 188 000 people have a myocardial infarct each year, and approximately 2.3 million people are living with CAD. , Occult CAD is common in those who present with other forms of atherosclerotic vascular disease, such as intermittent claudication or stroke, and is an important cause of morbidity and mortality in these patients. In the vast majority of patients, CAD is caused by atherosclerosis, but rarely it can occur as the result of aortitis ,vasculitis and autoimmune connective tissue diseases..  Atherosclerosis Atherosclerosis is a progressive inflammatory disorder of the arterial wall that is characterized by focal lipid-rich deposits of atheroma that remain clinically silent until they become large enough to impair tissue perfusion, or until ulceration and disruption of the lesion result in thrombotic occlusion or distal embolization of the vessel.  pathogenesis Early lesions have been found in the arteries of victims of accidental death in the second and third decades of life but clinical manifestations often do not appear until the sixth, seventh or eighth decade. During evolution of an atherosclerotic plaque, monocytes and other inflammatory cells bind to receptors expressed by endothelial cells. Subsequently, they migrate into the intima, and take up oxidized low-density lipoprotein (LDL) particles by phagocytosis to become lipid-laden macrophages or foam cells. Extracellular lipid pools appear in the intimal space when foam cells die and release their contents In response to cytokines and growth factors produced by activated macrophages, smooth muscle cells migrate from the media of the arterial wall into the intima, and change from a contractile to a fibroblastic phenotype, which can stabilize the atherosclerotic lesion. If this is successful, the lipid core will be covered by smooth muscle cells and matrix, producing a stable atherosclerotic plaque that will remain asymptomatic until it becomes large enough to obstruct arterial flow. In an established atherosclerotic plaque, macrophages mediate inflammation and smooth muscle cells promote repair. If inflammation predominates, the plaque becomes active or unstable and may be complicated by ulceration and thrombosis. Cytokines, such as interleukin-1, tumour necrosis factor-alpha, interferon-gamma, platelet-derived growth factors and matrix metalloproteinases, are released by activated macrophages. Any breach in the integrity of the plaque will expose its contents to blood and will trigger platelet aggregation and thrombosis that extend into the atheromatous plaque and the arterial lumen. This may cause partial or complete obstruction at the site of the lesion or distal embolisation, resulting in infarction or ischaemia of the affected organ. This common mechanism underlies acute coronary syndromes, as well as other manifestations of atherosclerotic disease such as lower limb ischaemia and stroke.  Risk factors for atherosclerosis -Non modifiable Age and gender Genetics -Modifiable Smoking Hypertension Hypercholesterolaemia Diabetes mellitus Haemostatic factors Physical activity Obesity Alcohol Diet Personality Social deprivation  Age and gender Age is the most powerful independent risk factor for atherosclerosis and gender also plays a role. Pre-menopausal women have lower rates of disease than men, although the gender difference disappears after the menopause.  Genetics Atherosclerotic CAD often runs in families and a positive family history is common in patients with early-onset disease (age < 50 in men and < 55 in women). Twin studies have shown that a monozygotic twin of an affected individual has an eightfold increased risk and a dizygotic twin a fourfold increased risk of dying from CAD, compared to the general population due to a combination of shared genetic, environmental and lifestyle factors.  Smoking There is a strong relationship between cigarette smoking and CAD, especially in younger (< 70 years) individuals, and this is probably the most important modifiable risk factor. Hypertension The incidence of atherosclerosis increases as BP rises, and this is related to systolic and diastolic BP, as well as pulse pressure. Antihypertensive therapy reduces cardiovascular mortality, stroke and heart failure.  Hypercholesterolaemia The risk of atherosclerosis rises with serum cholesterol concentrations and lowering serum total and LDL cholesterol concentrations reduces the risk of cardiovascular events. Diabetes mellitus This is a potent risk factor for all forms of atherosclerosis, especially type 2 diabetes mellitus. It is often associated with diffuse disease that is difficult to treat. Insulin resistance (normal glucose homeostasis with high levels of insulin) is associated with obesity and physical inactivity, and is also a risk factor for CAD  Haemostatic factors Platelet activation and high plasma fibrinogen concentrations are associated with an increased risk of coronary thrombosis. Antiphospholipid antibodies are associated with recurrent arterial thromboses Physical inactivity Regular exercise (brisk walking, cycling or swimming for 20 minutes two or three times a week) has a protective effect, whereas inactivity roughly doubles the risk of CAD and is a major risk factor for stroke.  Obesity Obesity, particularly if central or truncal, is an independent risk factor, although it is often associated with other adverse factors such as hypertension, diabetes mellitus and physical inactivity. Alcohol Excess alcohol consumption is associated with hypertension and cerebrovascular disease.  Diet Diets deficient in fresh fruit, vegetables and polyunsaturated fatty acids are associated with an increased risk of cardiovascular disease. Personality While certain personality traits are associated with an increased risk of coronary disease there is no evidence to support the popular belief that stress is a major cause of CAD.  Social deprivation Social deprivation is strongly related to cardiovascular disease. This may be partly due to associations with lifestyle risk factors, such as smoking and alcohol excess, which are more common in socially deprived individuals. Social deprivation does appear to be an independent risk factor for cardiovascular disease, however. Current guidelines recommend that treatment thresholds should be lowered for patients from socially deprived areas.  Management Two approaches can be employed. Primary prevention aims to introduce lifestyle changes or therapeutic interventions to prevent CAD and other forms of atherosclerosis in the whole population or in healthy individuals with an elevated risk of disease. Secondary prevention involves initiating treatment in patients who already have had an event, with the aim of reducing the risk of subsequent events.  Primary prevention The population-based strategy aims to modify the risk factors of the whole population through diet and lifestyle advice, on the basis that even a small reduction in smoking or average cholesterol, or modification of exercise and diet will produce worthwhile benefits. - Do not smoke - Take regular exercise (minimum of 20 mins, three times per week) - Maintain an ‘ideal’ body weight - Eat a mixed diet rich in fresh fruit and vegetables - Aim to get no more than 10% of energy intake from saturated fat  Primary prevention The targeted strategy aims to identify and treat high-risk individuals, who usually have a combination of risk factors that can be quantified by composite scoring systems. Thresholds for treatment vary in different countries. In the UK and North America, current guidelines recommend initiation of cholesterol and BP-lowering therapies in individuals with a 10-year cardiovascular risk of 7.5–10%.  Secondary prevention This involves targeting interventions at individuals who already have evidence of cardiovascular disease. Patients who recover from a clinical event such as an MI are usually keen to help themselves and are particularly receptive to lifestyle advice, such as dietary modification and smoking cessation. Additional interventions that should be introduced in patients with angina pectoris or an acute coronary syndrome are discussed in more detail in the next lectures. Thank you