401
edits
Atherosclerosis: Difference between revisions
no edit summary
No edit summary |
No edit summary |
||
| Line 120: | Line 120: | ||
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 /> | 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 /> | ||
# Acute narrowing of the vessel lumen: When the plaque ruptures, it will release its pro-coagulants to blood and that will lead to the formation of thrombus at the rupture site. The rupture often occurs at sites of erosion and fissuring on the fibrous cap surface. This thrombus may cause a complete occlusion of a particular vessel and result in ischemic necrosis (infarction) of the tissue that this particular vessel is supplying to. Clinically this is manifested as stroke, MI, gangrene of several organs such as intestine, spleen or lower extremities. These occlusiosn may also dissolve spontaneously due to pro-fibrinolytic enzymes such as streptokinase and tissue plasminogen activator (TPA). | # Acute narrowing of the vessel lumen: When the plaque ruptures, it will release its pro-coagulants to blood and that will lead to the formation of thrombus at the rupture site. The rupture often occurs at sites of erosion and fissuring on the fibrous cap surface. This thrombus may cause a complete occlusion of a particular vessel and result in ischemic necrosis (infarction) of the tissue that this particular vessel is supplying to. Clinically this is manifested as stroke, MI, gangrene of several organs such as intestine, spleen or lower extremities. These occlusiosn may also dissolve spontaneously due to pro-fibrinolytic enzymes such as streptokinase and tissue plasminogen activator (TPA). | ||
| Line 126: | Line 125: | ||
# Embolism: Embolization is the transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites. For example, fragments of thrombi in abdominal aorta may transfer to popliteal artery subsequently resulting in gangrene of the leg. Ulceration of atheroma may also produce ‘cholesterol crystal emboli’. This type of emboli is visualized as needle-shaped areas in affected tissues, mostly detected in the kidney. | # Embolism: Embolization is the transfer of the fragments of disrupted atheroma to distal vascular sites, which results into occlusion of those sites. For example, fragments of thrombi in abdominal aorta may transfer to popliteal artery subsequently resulting in gangrene of the leg. Ulceration of atheroma may also produce ‘cholesterol crystal emboli’. This type of emboli is visualized as needle-shaped areas in affected tissues, mostly detected in the kidney. | ||
# 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. | # 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. | ||
1.4 Risk factors of atherosclerosis<br /> | |||
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 /> | |||
Common risk factors<br /> | |||
Dyslipidemia<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 /> | |||
Incidence of atherosclerosis and coronary artery disease increases with higher levels of LDL particles. As mentioned earlier, LDL can accumulate in the intima of the artery in excess proportions and undergo chemical modifications that activate endothelial cells to proceed to atherosclerosis. When people generally refer to ‘bad cholesterol’, they are referring to LDL particles. On the other hand, high level of high-density lipoprotein (HDL) is ‘good cholesterol’ since it protects against atherosclerosis by reversing the cholesterol transport from peripheral tissues to the liver for disposal and functions as an antioxidant. In order to give additional clearance to what is ‘bad cholesterol,’ all lipid and lipoprotein abnormalities that are associated with higher coronary risk will be named subsequently: increased total cholesterol, increased LDL-cholesterol, low HDL-cholesterol, elevated total-to-HDL-cholesterol ratio, hypertriglyceridemia, increased non-HDL-cholesterol, elevated lipoprotein A, elevated apolipoprotein B (apo B is primarily found in LDL), decreased apolipoprotein A-I (apo A-1 is found in HDL), small and dense LDL particles, and several genotypes of apolipoprotein E (apoE influences cholesterol and triglyceride levels as well as the risk of coronary heart disease).<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 /> | |||
Lipid-Altering therapy<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 /> | |||
One of the most important strategies to reduce the complications of atherosclerosis is diet and exercise. In order to decrease cholesterol, Mediterranean diet is often recommended. Mediterranean diet consists of low animal fat, high olive oil, moderate energy consumption, nuts, vegetables, regular and moderate wine, lots of whole grains and beans. A meta-analysis of six randomized trials showed that Mediterranean diet led to greater reduction in total cholesterol than low fat diets among overweight/obese population. Mediterranean-styled diet in this context means replacement of saturated fats with polyunsaturated fats such as omega-3 fatty acid and α-linolenic acid. Polyunsaturated fats are potential anti-atherogenic due to its inhibiting action on cytokine-induced expression of leukocyte adhesion molecules at endothelial cells. Exercise and loss of excessive weight also contributes to improve abnormal lipid levels by reducing triglycerides and increasing HDL.<br /> | |||
In primary prevention, pharmacologic agents are the second option when lifestyle modifications fail to achieve targeted lipid profile. There are several groups of lipid-altering medicines such as HMG-CoA reductase inhibitors (statins), niacin, fibric acid derivatives, cholesterol intestinal absorption inhibitors, and bile acid-binding agents. In the clinical setting, statins are widely used, being the most cost-effective LDL-lowering drugs. They reduce intracellular cholesterol concentration by inhibiting HMG-CoA reductase, which is an enzyme that synthesizes cholesterol. This results into increased LDL-receptor expression and therefore leads to higher clearance of LDL molecules from blood. They also affect the liver and thereby lower the rate of VLDL synthesis, which results into lower levels of serum triglyceride. Statins also raise HDL, but this mechanism is not fully understood yet.<br /> | |||
Large studies, which have evaluated the effects of statin therapy, showed that ischemic cardiac events, the occurrence of MI and mortality rates were significantly reduced by implementing statin therapy. This significant improvement didn’t only apply for people with known preexisting atherosclerotic disease, but also for people within lower ranges of LDL, without preexisting atherosclerotic disease. For example, West of Scotland Coronary Prevention Study (WOSCPS trial) evaluated the effect of pravastatin on rates of nonfatal MI or CHD death, nonfatal MI, all cardiovascular deaths and total mortality among patients with hypercholesterolemia without preexisting CVD for five years. Use of pravastatin resulted in 31% risk reduction (p<0.001) in nonfatal MI or CHD death, and a 32% risk reduction (p=0.033) in all cardiovascular deaths as compared to the control group.<br /> | |||
Inhibiting HMG-CoA reductase results into several mechanisms that explain the beneficial effect of using statins. One beneficial mechanism is via lowering LDL and raising HDL. This results into less lipid content in atherosclerotic plaques and improve their biologic activity. Furthermore, anti-thrombotic and anti-inflammatory condition is enhanced by other mechanisms such as increased NO synthesis and fibrinolytic activity, inhibition of smooth muscle proliferation and monocyte recruitment, and reduced production of matrix-degrading enzymes by macrophages. Several studies suggest that other mechanisms also contribute to anti-inflammatory condition. For example, statins reduce endothelial expression of leukocyte adhesion molecules and macrophage tissue factor production by inhibiting the macrophage cytokines or by activating PPAR-α. Another anti-inflammatory action of statins, supported by clinical trials is reducing the serum level of C-reactive protein, which is a marker of inflammation. <br /> | |||
Although statin therapy can reduce the risk of atherosclerotic cardiovascular disease by about one third, there is still ned for additional risk-reducing therapies. Thus, a new idea was developed to raise HDL cholesterol as a treatment for atherosclerosis. With the finding of the high-HDL phenotype of a human genetic deficiency of cholesteryl ester transfer protein (CETP), a new class of drugs was developed, which inhibits CETP. CETP functions as a mediator for transfer of cholesteryl ester from HDL to VLDL/LDL, which is then cleared by LDL receptors in liver. Thus when CETP is inhibited, this transfer process is inhibited and the direct hepatic HDL clearance pathway takes over. This leads to less fractional clearance of HDL from plasma, which is beneficial for atherosclerosis. Although the absolute clearance rate of HDL remains the same, the key step for atherosclerosis, which is the removal of cholesterol from macrophage foam cells in artery wall by HDL, is reduced. <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 smoking<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 /> | |||
Tobacco smoking can lead to many mechanisms that contribute to atherosclerosis. Smoking is related with increased LDL level, decreased HDL level in blood and elevated insulin resistance. In addition it enhances oxidative modification of LDL by releasing free radicals and reduces generation of nitric oxide. This can promote endothelial dysfunction and thus lead to impairment of vasodilatation of coronary arteries and reduction of coronary flow reserve even in passive smokers. Tobacco smoking inappropriately stimulates sympathetic nervous system, increasing heart rate, blood pressure and perhaps coronary vasoconstriction. Smoking promotes prothrombotic environment through inhibition of endothelial release of tissue plasminogen activator, elevation of fibrinogen concentration in blood, enhancement of platelet activity (possibility related to sympathetic activation) and enhanced expression of tissue factor. Smoking can even damage the vessel wall and ultimately cause reduction of elasticity in vessel, enhancing the stiffness of vessel wall. Smoking has been associated with increased C-reactive protein and fibrinogen, suggesting correlation with inflammatory response, which is an important part of atherogenesis. There have also been findings that show higher expression of leukocyte adhesion molecules among smokers than nonsmokers. An elevation of homocysteine, an important biomarker of atherosclerosis has been associated with smoking. Smoking may additionally induce tissue hypoxia through displacement of oxygen with carbon monoxide in hemoglobin. <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 /> | |||
Lack of physical activity<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 /> | |||
Obesity<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 /> | |||
Diet<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 consumption<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 /> | |||
Psychosocial factors<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 /> | |||
Estrogen Status<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 /> | |||
In the past, hormone replacement therapy has been suggested by several studies due to the findings of potential athero-protective roles of estrogen. However, these findings were not confirmed in the randomized primary prevention studies of Women’s Health Initiative and HERS trial of secondary prevention. These studies showed that hormone replacement therapy (estrogen-progestin replacement) may increase cardiovascular risk in women and have no cardioprotective effect. Thus hormone replacement therapy is currently not recommended for reducing cardiovascular risk, due to its possible harmfulness according to current clinical trials. <br /> | |||
Biomarkers<br /> | |||
Biomarkers can serve to identify patients with subclinical atherosclerotic disease that are at risk of developing cardiovascular events.<br /> | |||
Homocysteine<br /> | |||
Homocysteine is an intermediary amino acid produced during the conversion of methionine to cysteine. A significant positive correlation was found between the serum levels of homocysteine and the incidence of cardiovascular diseases. Although the clear mechanism of this correlation is undetermined, the overall result of the most current evidence suggests that homocysteine can modestly contribute to cardiovascular risk by inducing vascular injury. Homocysteine promotes oxidative stress, intimal thickening, disruption of elastic lamina, hypertrophy of smooth muscle cells, vascular inflammation platelet accumulation and production of occlusive thrombi when elevated in blood. Several conditions can cause hyperhomocystinemia, such as genetic defects in methionine metabolism or insufficient consumption of folic acid, which is involved in the methionine pathway. Such disorders cause premature and severe atherosclerosis. Despite this observational relationship, there is no data yet that proves reducing high serum level of homocysteine will lead to a decrease in atherosclerosis or its complications.<br /> | |||
Lipoprotein A<br /> | |||
Some studies have concluded that lipoprotein A is an independent risk factor for coronary artery disease. As lipoprotein A contains apo A, which structurally resembles plasminogen, lipoprotein A interferes with fibrinolysis by competing with plasminogen binding with molecules. This leads to impairment of plasminogen activation, plasmin generation and lysis of fibrin clots. In addition, lipoprotein A binds with macrophages through a high-affinity receptor, promoting foam cell production and deposition of cholesterol in atherosclerotic plaques. As with homocysteine, not all studies support this theory of correlation, although increased risk of cardiovascular events appear to correlate with people with highest lipoprotein A serum level.<br /> | |||
C-Reactive Protein and other markers of inflammation<br /> | |||
Since the participation of inflammatory cells and mediators in atherosclerosis is well established, markers of inflammation have received a lot of attention from the researchers. Several markers of inflammation such as C-reactive protein (CRP), fibrinogen and amyloid A are produced by hepatocytes in an acute phase under the influence of cytokines such as IL-6 when they mobilize from intima to the liver during the fatty streak stage. From these markers, CRP has shown the greatest association with atherosclerosis as a marker of low-grade systemic inflammation. A significant association between elevated CRP level in blood and prevalence of atherosclerosis has been shown in more than 30 epidemiologic studies. Different studies showed that higher basal CRP levels (four-fold higher) were found grouping patients with MI as compared to controls. Several studies have proposed that elevated plasma CRP can be an independent predictor for many cardiovascular diseases based on the result that CRP plasma value was able to predict the long-term risk of first MI, ischemic stroke or peripheral vascular disease among the male group. In addition, recent studies have shown that CRP also has a role as a mediator in atherogenesis. By inducing adhesion molecule expression and release of IL-6 and monocyte chemoattractant protein-1 via endothelial cells, CRP sustains inflammatory state of atherosclerosis by recruiting monocytes and lymphocytes.<br /> | |||
Infection<br /> | |||
A variety of infectious agents such as Chlamydia pneumonia, cytomegalovirus and Helicobacter pylori were identified in the lesions of atherosclerosis and this observation raised a suggestion that these infectious agents may contribute to atherogenesis. However, to date the definite proof of this theory is lacking and also there haven’t been any clinical studies that showed significant relationship between the antibiotic treatment against these infectious agents and the risk of cardiac events of the survivors of acute coronary syndromes. Chlamydia is a strong candidate among other infectious agents, since they produce heat shock protein 60 (HSP-60) that activates macrophages and stimulates the production of matrix metalloproteinases. Furthermore, HDP-60 can also stimulate foam cell formation, lipoprotein oxidation, and increased pro-coagulant activity, which are the major attributing components of atherosclerosis. Although there is no evidence to date, some researchers believe that exogenous pathogens can cause endothelial injury and inflammation that can lead to initiation or exacerbation of atherosclerosis.<br /> | |||
Co-morbidity groups<br /> | |||
Hypertension<br /> | |||
Hypertension is defined as a systolic blood pressure (SBP) ≥ 140mmHg and/or a diastolic blood pressure (DBP) ≥ 90mmHg. Elevated blood pressure is a well established risk factor of atherosclerosis, including mortality from coronary heart disease and stroke. For example, cardiovascular disease doubles with every 20 mmHg increase in SBP or every 10 mmHg increase in DBP.<br /> | |||
One of the mechanisms of hypertension in contributing to atherosclerosis is injury of vascular endothelium by elevated hemodynamic stress. Injury of endothelium may increase the permeability of the vessel wall to lipoproteins. Increased blood pressure may also increase the number of scavenger receptors on macrophages, which enhances the development of foam cells. Furthermore, increased cyclic circumferential strain in hypertensive arteries can result into promoting LDL accumulation in the intima and facilitation of their oxidative modification. Finally, hypertension can contribute to atherogenesis due to the presence of Angiotensin II, which not only works as a vasoconstrictor, but also as a pro-inflammatory cytokine. <br /> | |||
Antihypertensive therapy <br /> | |||
Antihypertensive therapy can either consist of lifestyle interventions or pharmacotherapy. Lifestyle modifications consist of diet, body weight reduction, increased activity, and cessation of smoking. As for diet, high consumption of fruits, vegetables, dairy products low in fat, fish oils, potassium and reduced consumption of sodium and alcohol are recommended. | |||
The indication for pharmacotherapy depends on the severity of hypertension and on the assessment of total CVD risk. Several large trials have shown that pharmacotherapy for hypertension can substantially reduce major cardiovascular events such as MI and stroke. Drug therapy is indicated when chronic SBP ≥ 160mmHg and/or DBP ≥100mmHg, or if target organ damage is present.<br /> | |||
With estimated global incidence of 170 million people, diabetes mellitus is a large problem worldwide. Diabetes mellitus increases the risk of acute coronary events by three- to five folds and 80% of diabetic patients will face atherosclerosis-related cardiovascular diseases. Risk for atherosclerosis among diabetics is considered to be as high as grouping patients with previous MI. Based on this observation, the National Cholesterol Education Program report from the United States and guidelines from Europe consider type 2 diabetes to be a CHD equivalent, categorizing it to the highest risk for MI.<br /> | |||
There are several possible mechanisms that make this group particularly vulnerable to atherosclerosis. An example of mechanism is non-enzymatic glycation of lipoproteins, which promotes uptake of cholesterol by scavenger macrophages. Furthermore, pro-thrombotic and anti-fibrinolytic properties of diabetes can also contribute to this vulnerability. The high prevalence of endothelial dysfunction among diabetes group leads to reduced bioavailability of NO and enhanced leukocyte adhesion. The most effective prevention of atherosclerosis among diabetes group is tight regulation of serum glucose levels. This intervention significantly reduces the risk of microvascular complications such as retinopathy and nephropathy. Furthermore, intense anti-diabetic regime also reduced macrovascular outcomes such as MI and stroke among a group of diabetes type 1. Additionally managing hypertension and dyslipidemia among diabetic groups also significantly reduces the risk of cardiovascular diseases.<br /> | |||