THE ODDS RATIO FOR CORONARY HEART DISEASE ASSOCIATED WITH THE PRIMARY RISK FACTORS View this Information

"Assisting Physicians to Develop Customized Care Plans to Prevent Heart Attacks and Cardiovascular Disease Based on Genotyping"

Bioheart has assembled an assortment of genotype tests that will identify the possible presence of polymorphisms (variances) in certain key genes, which can lead to increased risk of heart disease.

The presence of these polymorphism does not mean that a person will necessarily develop heart disease. The presence of these gene polymorphisms when combined with other environmental factors including, smoking, high risk dietary habits, overweight, inadequate exercise or other factors, may place the individual at higher than normal risk for heart disease.

By identifying the presence of these polymorphisms a person can be alerted to the higher risk and therefore make an extra effort to follow well documented measures to reduce the risk for heart disease, such as; reducing cholesterol intake, exercising, maintaining proper weight, stopping smoking, controlling stress, reducing salt intake, etc.

The association between these gene polymorphisms and increased risk of heart disease will be always be more pronounced in younger persons. In most studies a distinction is made between those over, and those under, 45 to 55 years of age with higher associations with disease being observed in the younger patients.

Additionally, it is important to note that for the most part, the data presented here was taken from clinical studies involving Europeans or those of European ancestry. Therefore, the evidence to support the usefulness of these gene tests in other ethnic groups is either weaker or nonexistent. In many cases the frequency rates of these polymorphisms in other ethnic groups is less than in the Caucasian population. This is especially true for Asian groups who often have very low frequency rates of many of these polymorphisms.

THROMBOGENIC PANEL

This assortment of genetic tests will identify the possible presence of four relatively common polymorphisms associated with increased susceptibility to blood clot formation. The formation of blood clots in the arteries that feed the heart can lead to heart attack. Unfortunately a third of heart attacks are fatal therefore leaving the victim no opportunity to take corrective action. For this reason it is important to identify heart attack susceptibility prior to the event.

The Thrombogenic Panel consists of the following gene tests:

• Pl^A2 - This gene polymorphism has been associated with a 3 to 6 fold increased risk for thrombosis (blood clot formation) in the coronary arteries which is a primary precursor to heart attack. It has also been found that this polymorphism is associated with a higher risk for stent restenosis and coronary artery disease. This polymorphism is seen in 25% to 30% of Caucasian coronary artery disease patients. Pl^A2 Information

• Factor V ^Leiden - This relatively common polymorphism found in 2% to 5% of the general population. Factor V Leiden has been associated with increased risk for heart attack especially when present with other risk factors such as smoking, hypertension, diabetes mellitus or obesity where the combined factors are associated with a 3 to 6 fold risk for myocardial infarction (heart attack). Additionally, this polymorphism is also strongly associated with venous thrombosis especially when found along with the Prothrombin G20210A polymorphism. The Factor V Leiden gene polymorphism has been associated with a 8 fold or greater increased risk for venous thrombosis. Some experts suggest that women with this gene mutation should be encouraged to avoid oral contraceptives.
  Factor V Information

• Prothrombin G20210A - This polymorphism is found in 2% to 3% of the general population. Like the Factor V Leiden gene polymorphism, the prothrombin polymorphism is associated with higher risks for both myocardial infarction and venous thrombosis. When found in association with the Factor V Leiden gene polymorphism, the combined effect is even more dangerous. Alone the Prothrombin polymorphism is associated with a 3 to 5 fold increased risk of venous thrombosis (blood clot in the veins, and generally in the extremities). Like the Factor V Leiden polymorphism, women with the Prothrombin polymorphism are often encouraged to avoid oral contraceptives.
  Prothrombin G20210A Information

• MTHFR - This polymorphism in the methylenetetrahydrofolate reductase gene is found in approximately 5% of the general population and leads to elevated homocysteine levels. This polymorphism is associated with a 3 fold increased risk of coronary artery disease. People found to carry this gene polymorphism are often encouraged to increase folic acid intake. MTHFR Information

HDL (High Density Lipoprotein) CHOLESTEROL PANEL

High Density Lipoprotein, the so called; "good cholesterol", is important in transporting and clearing cholesterol from the blood. In some cases, gene polymorphisms can improve the efficiency of HDL and reduce one's risk of coronary artery disease (CAD) below that of the general population. In other cases, gene polymorphisms interfere with normal function and increase the risk for CAD. Related Info

The HDL Cholesterol Panel consists of the following gene tests:

• APO A-I - Apolipoprotein A-I has two polymorphisms of interest, one found in approximately 4% of the general Caucasian population, leads to decreased levels of HDL and thus raises one's risk for CAD, the other found in approximately 20% of Caucasians and 45% of Chinese leads to increased levels of HDL and thus lowers the risk for CAD except in smokers or women. APO A-1 Information

• APO A-IV - Apolipoprotein A-IV also has two polymorphisms of interest, and like Apo A-I, one raises the risk for CAD and the other lowers the risk. The polymorphism that reduces the risk for CAD through elevated HDL levels and lower triglyceride levels is found in approximately 15% of Caucasians and 12% in Hispanics. This polymorphism is not found to be protective in smokers or the obese where the risk may then become higher than in the general population. The other polymorphism seen in approximately 33% of the population causes higher LDL and triglyceride levels and increases the risk for CAD. However, this higher risk group may also be more positively responsive to dietary changes. APO A-IV Information

• CETP TAQ 1 B - The Cholesteryl Ester Transfer Protein (CETP) Taq 1 B polymorphism increases plasma CETP concentrations with the result of higher plasma HDL levels. Patients with this polymorphism are at higher risk for coronary artery disease (CAD) but respond to the cholesterol lowering drug pravastatin better, in terms of slower progression to CAD, than those without the polymorphism. CETP TAQ1 B Information

• LPL - Lipoprotein Lipase has three polymorphisms of primary interest which result in elevated triglyceride levels coupled with reduced HDL levels thus increasing the risk for CAD. One polymorphism found in 0.2% of the population increases the risk for ischemic heart disease 4.9 times. The other two polymorphisms are found in approximately 2% to 5% of the population and are associated with a 20% to 40% fold increased risk of ischemic heart disease.

LDL (Low Density Lipoprotein) CHOLESTEROL PANEL

LDL Cholesterol is the form of cholesterol that, in excessively high levels, can lead to coronary artery disease. When one adopts a diet that is "low in cholesterol" this is the cholesterol that one is trying to limit the consumption of. Exercise, diet and certain other modifications can increase HDL levels, which, in turn help control LDL levels and thus reduce the risk of heart disease. These gene tests can be useful in identifying one's predisposition to high LDL and triglyceride levels.

The LDL Cholesterol Panel consists of the following gene tests:

• APO B-100 - This polymorphism interferes with Apo B binding domain and results in impaired LDL clearance and thus elevated LDL levels. This polymorphism has been associated with a 7-fold increase in risk for coronary artery disease. APO B-100 Information

• APO C-III - Lipoproteins containing the apo C-III S2 allele have impaired binding affinity to receptors on liver cells and thus apo C-III laden lipoproteins accumulate in the blood giving rise to elevated LDL, triglyceride and VLDL triglycerides. The apo C-III polymorphism found in approximately 5% to 10% of the population, is associated with a 5 fold increased risk for hypertriglyceridemia.
  APO C-III Information

• APO E - Apolipoprotein E has two polymorphisms of significance to heart disease risk. 12% to 28% of Caucasians carry at least one copy of the Apo E epsilon 4 polymorphism. On average, these persons will have 10% higher cholesterol levels and a 40% greater risk for coronary artery disease. Those who survive a first heart attack will be at twice the risk for death than those without the Apo E epsilon 4 polymorphism. Additionally, those who carry the Apo E epsilon 4 polymorphism along with at least one copy of the ACE D allele are at a 16-fold higher risk for restenosis following coronary angioplasty. Related Info | APO E Information

HYPERTENSION PANEL

The genes in this Hypertension Panel are play an important role in blood pressure regulation. These genes play an important role in blood vessel wall function affecting vascular tone, smooth muscle cell migration and proliferation and other endothelial cell activities and functions. These gene polymorphisms have been associated with hypertension, coronary artery disease (CAD) and heart attack or myocardial infarction (MI) and restenosis (re-narrowing of vessels) following procedures designed to return blood flow through blocked vessels.

The Hypertension Panel consists of the following gene tests:

• ACE (Angiotensin-I Converting Enzyme) DD Genotype polymorphism. The DD genotype in the ACE gene, found in 12% to 30% of the population, is associated with a 2 times higher risk for CAD in men, 2 times the rate of restenosis for each D allele, a 2.2 times the risk for CHD (Congestive Heart Failure), 2.5 times the risk for MI (Myocardial Infarction), a 3.9 times the risk for a larger ischemic injury following occlusion, higher common carotid artery intima-medial thickness, and better response to fluvastatin to reduce cholesterol. ACE Information

• AT1R (Angiotensin II Type 1 Receptor) CC genotype polymorphism. In approximately 2% of clinical cardiovascular patients, the ACE DD genotype and AT1R CC genotype are found together. This combination is associated with a 2.4 times greater risk of malignant ventricular arrhythmias for which it is suggested that early pharmacologic intervention with inhibitors, could prevent some cases of sudden death. Additionally the ACE DD genotype together with the AT1R CC genotype is also a synergistic risk factor for CAD with a 5.32 times greater risk and for MI with a 13.3 times greater risk. AT1R Information

• eNOS (Endothelial Nitric Oxide Synthase) TT genotype polymorphism. This genetic variation, found clinically in approximately 11% to 15% of patients, leads to dysregulation of vascular tone, platelet aggregation, leukocyte adhesion and smooth muscle proliferation thus promoting coronary athersclerosis and thrombosis. The TT genotype is associated with a 4.2 times greater risk for angiograhic CAD, a 2.5 times greater risk for MI and a 2.3 times higher risk of essential hypertension. The data presented here appears to hold for both Caucasian and Japanese cohorts.

MISCELLANEOUS CARDIOVASCULAR RISK PANEL

The tests that are shown in this panel cannot be categorized under any of the existing panels but they do have a significance for their associations with cardiovascular disease.

• HFE - The human hemochromotosis associated gene mutation is associated with twice the risk of a first heart attack in men. 10% of the general population carry at least one copy of the HFE gene mutation. The genetic test for the HFE gene polymorphism is marketed by Bioheart as the Iron Sensitivity Test". This gene polymorphism has been linked through studies to iron intake and heart disease. Hemachromatosis is a disease which allows too much iron to be absorbed from food. Utrecht University published a study of 12,239 women. Those who had just one copy of the hemochromatosis gene had double the risk of dying from heart disease or stroke, this data was confirmed by a similar study at the University of Kuopio in Finland.

HFE Information | Related Info on the Iron Sensitivity Test"