Coronary heart disease develops due to narrowing of the blood vessels, a process known as atherosclerosis. This process of atherosclerosis develops slowly over a number of years.
Then, one day a clot forms at the site of the narrowed blood vessel and acutely shuts down the blood flow to a portion of the heart. This is what causes an acute heart attack or technically speaking, angina (minor episode without any damage to heart muscle) or acute myocardial infarction (prolonged episode with damage to the heart muscle).
A person who has coronary heart disease frequently also has low HDL cholesterol, high triglycerides, high blood pressure, abdominal obesity and pre-diabetes or diabetes.
A number of excellent medical studies have clearly shown these metabolic disorders to be the major risk factors for coronary heart disease.
Intense medical research in the last decade has shown that all of these medical disorders have a common thread. This common thread is insulin resistance. Therefore, collectively, these disorders are known as Insulin Resistance Syndrome, also known as Syndrome X or Metabolic Syndrome.
Insulin Resistance Syndrome has, therefore, emerged as the root cause for coronary heart disease in a majority of patients.
Insulin resistance causes narrowing of the blood vessels and puts you at high risk for a heart attack due to the following.
1. High level of insulin.
Insulin resistance means that your body becomes less sensitive to certain actions of your own insulin. One of these actions is to drive glucose from blood into the cells. In order to compensate for this insulin resistance, your pancreas is able to produce large quantities of insulin, which keeps blood glucose normal for a long time. This compensatory high level of insulin, however, is not good for the body.
A high insulin level in the blood due to insulin resistance is now a well-established risk factor for heart disease .
A high level of insulin stimulates smooth muscle cell proliferation in the arterial wall and causes thickening and stiffness of the arterial wall which in turn, contributes to narrowing of the coronary blood vessels.
Several, large excellent clinical studies have clearly shown high insulin level to be a major risk factor for coronary heart disease.
In one such study, the Helsinki Policemen Study, investigators measured blood insulin level in 982 healthy men aged 35-64 during an Oral Glucose Tolerance Test. A nine and a half year follow-up of these individuals showed that the insulin level was clearly associated with the risk for coronary heart disease.
In another study from Finland, 909 diabetic and 1,373 non-diabetic individuals were studied. Blood insulin level was found to have a correlation with coronary heart disease in these individuals.
In the Paris Prospective Study, 7,164 working men aged 43-54 were studied for risks for heart disease. After a mean follow-up of 11.2 years, blood insulin level was found to be a strong predictor of heart disease.
In a Danish Study, 504 men and 548 women were followed for 17 years. Blood insulin level was found to a strong predictor of heart disease.
In Quebec, Canada, researchers studied 797 men and 322 women and found a strong correlation between blood insulin level and coronary heart disease.
2. High blood pressure.
High blood pressure is known to cause narrowing of the arterial blood vessels, including coronary arteries of the heart.
Blood pressure higher than 115/80 increases your risk for a heart attack.
Blood pressure above 130/80 is called hypertension.
A healthy blood pressure is less than 110/70 in most individuals.
Insulin resistance is present in the majority of patients with hypertension. This association between insulin resistance and hypertension has been shown in several excellent studies.
Several studies have found high insulin level to be associated with the risk for hypertension.
High insulin level causes high blood pressure by the following mechanisms:
It causes thickening of arterial walls, which then become stiff. There is increased resistance to blood flow through these stiff blood vessels, which leads to increase in blood pressure.
It causes retention of sodium and water from the kidneys, which then leads to high blood pressure.
It contributes to sympathetic nervous system over-activity, which causes constriction of blood vessels, which then leads to high blood pressure.
3. High Triglycerides and Low HDL cholesterol.
Individuals with Insulin Resistance Syndrome typically have high triglycerides and low HDL cholesterol .
In normal individuals, one of the functions of insulin is to suppress the breakdown of fat from the fat cells into the blood stream. This action of insulin is hampered in individuals with insulin resistance. As a result, there is an exaggerated breakdown of fat from the fat cells. The product of this fat breakdown is called free fatty acids.
Thus, in individuals with insulin resistance, there is a high level of free fatty acids in the blood. The liver takes up these free fatty acids and converts them into VLDL cholesterol (Very Low Density Lipoproteins). These cholesterol particles are rich in triglycerides and therefore, individuals with insulin resistance have a high level of triglycerides on their cholesterol blood test.
VLDL particles interact with HDL particles and exchange their triglycerides for the cholesterol of HDL particles. This results in a decrease in HDL cholesterol.
The more VLDL you have, the more triglycerides transfer to HDL cholesterol in exchange for cholesterol and more lowering of HDL cholesterol takes place.
These triglycerides-enriched HDL particles also break down easily which further lowers HDL level. This is exactly what happens in patients with Insulin Resistance Syndrome who have high level of VLDL (triglycerides rich particles).
HDL works as a scavenger. It cleans out cholesterol particles that build up in the walls of blood vessels. Low HDL cholesterol means less cleansing of the cholesterol build-up in the vessel wall. That’s why low HDL is a major risk factor for narrowing of coronary blood vessels .
VLDL particles also give rise to the formation of another cholesterol particle, known as IDL (Intermediate Density Lipoprotein), which then converts to LDL (Low Density Lipoproteins). VLDL, IDL and LDL particles deposit in the arterial wall, which causes narrowing of the vessel wall.
4. Increase in the small dense LDL cholesterol particles.
LDL (bad cholesterol) consists of two subpopulations: small, dense particles and large, fluffy particles. Small, dense particles deposit more easily inside the blood vessel wall as compared to the large, fluffy particles.
In patients with Insulin Resistance Syndrome, there is a preponderance of these harmful, small, dense LDL particles, which more easily deposit into the arterial wall and leads to narrowing of the coronary blood vessels.
Individuals with Insulin Resistance Syndrome have a build-up of bad cholesterol (LDL, VLDL and IDL) in their blood vessels. Due to low HDL cholesterol, they cannot clean out this build-up of gunk. The net result is narrowing of the blood vessels, including coronary arteries, setting up the stage for heart attacks
5. Increased tendency for clot formation and decreased ability to break the clot.
In patients with Insulin Resistance Syndrome, there is a high level of several clotting factors including fibrinogen level in the blood, which increases the risk for clot formation. In addition, these patients also have a decreased ability to break the clot due to a high level of a substance known as PAI-1, short for Plasminogen Activator Inhibitor-1.
Consequently, individuals with Insulin Resistance Syndrome are at high risk for clot formation and have decreased ability to break these clots.
When such clots form in the already narrowed coronary blood vessels, a person suffers an acute heart attack.
6. High CRP (C-reactive Protein) level.
CRP is an easily available blood test in most laboratories. Recently, there has been tremendous interest in CRP among researchers in the field of atherosclerosis (or narrowing of the blood vessels).
CRP indicates ongoing inflammation. Inflammatory cells are present in atherosclerotic plaque and can make it susceptible to rupture. A clot forms at the ruptured plaque leading to an acute heart attack.
A high level of CRP has been found to be associated with significantly higher risk for heart attack.
Individuals with insulin resistance have a high level of CRP and therefore, are at high risk for heart attack.
7. Endothelial Dysfunction.
The endothelium is the lining of the blood vessel wall. The endothelium produces a number of substances, a balance of which is important for its own healthy functioning.
A number of these substances can cause constriction of the vessel wall (vasoconstriction) whereas the others cause a dilatation of the vessel wall (vasodilatation).
In normal individuals, there is a fine balance between these two processes. Patients with insulin resistance have disruption in this balance in such a way that there is more vasoconstriction and less vasodilatation. This endothelial dysfunction causes further narrowing of the blood vessels.
The association between endothelial dysfunction and insulin resistance has been well documented in several studies in diabetic as well as non-diabetic patients.
8. High blood glucose level (pre-Diabetes, Diabetes).
Diabetes is a rather late event in the progression of insulin resistance. Many patients die of a heart attack before they are even diagnosed with diabetes. Diabetics usually have high blood pressure, low HDL cholesterol, high triglycerides level, high fibrinogen level, high PAI-1 level and endothelial dysfunction.
It's no surprise that most diabetics have developed significant narrowing of the blood vessels by the time they are diagnosed with diabetes.
Diabetics have about a four fold higher risk for heart disease than non-diabetics. Pre-diabetes is also associated with a high risk for heart attack. This condition is diagnosed using a two hour Oral Glucose Tolerance Test.
In the famous Honolulu Heart Study, a direct relationship was found between the one hour blood glucose (in a glucose tolerance test) and risk for heart disease in pre-diabetic as well as diabetic individuals.
In a twenty year follow-up of three famous European studies, the Whitehall Study, the Paris Prospective Study and the Helsinki Policemen Study, a direct relationship was again found between the two hour glucose (in a glucose tolerance test) and risk of death from heart disease .
In summary, insulin resistance is the underlying cause for a heart attack in a majority of people. Therefore, diagnosis and treatment of Insulin Resistance Syndrome is the key to prevention of heart attacks.
This article was written by Sarfraz Zaidi, MD, FACE. Dr. Zaidi specializes in Diabetes, Endocrinology and Metabolism.
Dr. Zaidi is a former assistant Clinical Professor of Medicine at UCLA and Director of the Jamila Diabetes and Endocrine Medical Center in Thousand Oaks, California.
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