Atherosclerosis: Difference between revisions

The concept of ‘vulnerable plaque’ has developed into a new concept of ‘vulnerable patient’ as the concept of pathogenesis of atherosclerosis was linked to a person’s susceptibility to coagulation and thus vascular events, which can be influenced by many personal factors such as genetics (e.g. procoagulant prothombin gene mutation), coexisting condition (e.g. diabetes), and lifestyle factors (e.g. smoking, obesity).<br />

The clinical complications of atherosclerosis are highly dependent on the location and size of affected vessels, the duration of the chronic process, and the type of plaque, since the severity of impairment of atherosclerosis differs throughout the vasculature. For example, ‘stable plaque’ can easily result into angina pectoris due to its thick fibrous cap that directly affects the diameter of the relatively small coronary vessels. On the other hand, ‘vulnerable plaque’ is non-stenotic, but can easily cause acute thrombosis and therefore myocardial infarction due to its fragility towards rupture when located at physically stressed areas such as bifurcations. Often with ‘vulnerable plaques’ there are relatively few symptoms, however they are more numerous and dispersed throughout the arteries compared to ‘stable plaque’. Thus, you can either have an occlusion due to the growing plaque or due to the embolization of the ruptured fragments of the original plaque. Due to the difficult detection of ‘vulnerable plaques’ while they are widely dispersed, it is highly important to tackle the risk factors prior to plaque rupture. Thus in the following paragraph, we will highlight the clinical risk factors associated with atherosclerosis. The four major clinical consequences of atherosclerosis are listed and explained below.<br />

# Aneurysm: After a chronic period, atherosclerotic lesion may extend into the medial layer, resulting into atrophy and loss of elastic tissue. This can subsequently cause dilatation and weakness of the artery, forming aneurysm. Over time, aneurysm may suddenly rupture and result into life-threatening situation for the patients.

Recent studies have shown that atherosclerosis is not just the inevitable process of aging, but also a process with many modifiable components. A worldwide INTERHEART study has established the importance of nine potentially modifiable risk factors for atherosclerosis, which account for over 90% of the population-attributable risk of a first MI (figure 12). A variety of non-modifiable risk factors such as advanced age, gender and hereditary coronary heart disease are important to recognize in patients with atherosclerosis. Recently the role of several biological markers associated with the development of cardiovascular events are accentuated since one out of five cardiovascular events occur in patients lacking the earlier mentioned risk factors. <br />

One of the major modifiable risk factors for atherosclerosis is hypercholesterolemia. Study shows that dyslipidemia (defined as an elevated apo B to apo A-1 ratio) was responsible for 49% of the population-attributable risk of a first MI. In countries with high consumption of saturated fat and high cholesterol levels (e.g. the United States), observational studies have shown that the mortality rates from coronary disease are higher compared with those in countries with traditionally low consumption of saturated fat and cholesterol levels (e.g. Japan). Several trials have shown that the risk of ischemic heart disease positively correlates with higher total serum cholesterol levels. For example, the impact of hypercholesterolemia can be illustrated by an observational result from the Framingham Heart Study, which shows that a person with a total cholesterol level of 240 mg/dl has twice the coronary risk a person would have with a cholesterol level of 200 mg/dl. However, it is a mistake to think that all lipoproteins consisting of cholesterol are harmful since cholesterol can provide critical functions to all cells that need to form membranes and to synthesize products such as steroid hormones and bile salts. <br />

There are several causes to persistent elevated level of LDL, such as high fat consumption or genetic abnormalities (e.g. familial hypercholesterolemia). Familial hypercholesterolemia is a condition with genetically defected LDL receptors that cannot efficiently dispose LDL from the circulation. There are two types of this disease with different manifestations. Patients with the heterozygote type have only one defective gene for the receptor and suffer from high serum level of LDL, easily developing atherosclerosis. Homozygotes have a complete lack of normal LDL receptors and thus may experience cardiovascular events already in the first decade of life. In the absence of genetic abnormalities, the quantity of cholesterol in serum is strongly related to the high saturated fat consumption.<br />

Controlling the serum lipid level is a key step to limit the consequences of atherosclerosis. Major clinical trials show that coronary events and mortality significantly decreased when total and LDL-cholesterol levels were reduced by primary and secondary prevention.<br />

The most recently investigated CETP inhibitors are torcetrapib, anacetrapib, and dalcetrapib. In the Investigation of Lipid Level Management to Understand Its Impact in Atherosclerotic Events (ILLUMINATE) trial, involving 15,000 patients at high risk for coronary heart disease, torcetrapib was clinically investigated. Unfortunately this trial was prematurely stopped due to the finding of an increase in cardiovascular events associated with its use. Anacetrapib and dalcetrapib are still under active clinical investigation, since they differ in their mechanism of working from torcetrapib.<br />

Tobacco use is known to increase the risk of atherosclerosis and ischemic heart disease based on numerous studies. For example, INTERHEART study shows that smoking is responsible for 36% of the population-attributable risk of a first MI. Other studies showed that smoking is an independent major risk factor for coronary heart disease, cerebrovascular disease and total atherosclerotic cardiovascular disease.  The Atherosclerosis Risk in Communities Study measured the direct effect of smoking on the development of atherosclerosis. They measured intima-medial thickness of the carotid artery of 10,914 patients for three years with ultrasound. Their result showed that current smokers had 50% increased progression of atherosclerosis in comparison to nonsmokers during the study period. Also patients with environmental tobacco smoke exposure (passive smokers) had 20% higher rate of atherosclerotic progress versus patients without environmental smoke exposure.<br />

Quitting smoking is known as one of the most effective preventive measures of CVD and their complications. Soon after the cessation cardiac risk due to smoking decrease in a short period and continue to diminish when cessation is permanently preserved. The risk for cardiovascular diseases Among patients with coronary heart disease, cessation of smoking decreases the risk of cardiac events by 7-47%. Not only does cessation of smoking reduce risk of CVD, but also substantially reduce the risk of all-cause mortality.<br />

   

   

INTERHEART study showed that lack of exercise was accountable for 12% of the population-attributable risk of a first MI. Recent evidence shows that physical activity of even moderate degree can protect against coronary heart disease and all-cause mortality .The beneficial effects of physical exercise are decrease of triglyceride levels and blood pressure, elevation of HDL, enhancement of insulin sensitivity and production of NO by the endothelial cells, and weight loss. Although large scale randomized primary prevention trials are lacking, physical activity should be promoted to anyone with risk of developing atherosclerosis.<br />

   

The American Heart Association has published an article, identifying obesity as an independent risk factor for coronary heart disease. Obesity is correlated with several risk factors for atherosclerosis such as hypertension, insulin resistance, glucose intolerance, decreased HDL serum level and hypertriglyceridemia. Weight loss is an important treatment to prevent many obesity-related risk factors for atherosclerosis that has just been mentioned. <br />

Several studies suggest that diet, more specifically intake of fruit and vegetable can reduce the risk of coronary heart disease and stroke. In the INTERHEART study, lack of daily consumption of fruits and vegetables was responsible for 14% of the population-attributable risk of a first MI. Another meta-analysis study showed that additional daily portion of fruit reduced the risk of stroke by 11%, but no such effect was found with vegetable consumption.  Another form of diet such as high fiber consumption can also relatively reduce the risk of coronary heart disease and stroke compared to low fiber consumption. In addition, the Hale project has shown that Mediterranean-styled diet as primary prevention for CVD among elderly aged 70-90 without CVD significantly reduces all-cause, coronary heart disease and CVD mortality.<br />

Alcohol is harmful when used chronic or excessive and can lead to various complications such as liver and heart failure, increased cancer risk, neurological complications and injuries. However despite these adverse effects, moderate drinking (US parameters; women: <2 drinks per day, men: <3 drinks per day) may have protective benefits in regard to coronary heart disease according to several prospective cohort studies. These studies showed moderate drinking resulted in reduction of risk in coronary heart disease by 40-70% compared to no or heavy drinkers. This beneficial effect was seen in various groups of people without or with known risk for coronary heart disease and adults older than 65 years old. In a meta-analysis study, alcohol drinkers had lower relative risk for CVD mortality (0.75, 95% CI 0.70-0.80), coronary heart disease mortality (0.75, 0.68-0.81) and incidence of coronary heart disease (0.71, 0.66-0.77) than nondrinkers.<br />

Mentioned by INTERHEART study, psychosocial factors may directly contribute to the early development of atherosclerosis. Psychological stress may directly damage endothelium and indirectly aggravate other common risk factors such as smoking, dyslipidemia and hypertension. Due to the difficulty in quantifying the extent of atherosclerosis, studies showing the relationship between stress and atherosclerosis have been limited. Epidemiologic studies have shown stronger link between psychosocial factors (loss of job, depression and bereavement) and MI and sudden death. <br />

Women and men have different risk for cardiovascular diseases throughout life. For example, at young age, men have an estimated four- to fivefold higher risk than women. However this difference diminishes and the age point of this is strongly related to the moment of menopause.  From this observation, it has been suggested that estrogen may play athero-protective roles, since the levels of estrogen declines after menopause. In premenopausal women, estrogen raises HDL levels and reduces LDL levels in blood. Estrogen can even exhibit antioxidant and antithrombotic properties and can improve endothelium-dependent vasodilatation.<br />