Heart disease is a complex condition that develops slowly and sometimes silently—and it is well-known that heart disease is the top cause of death in the United States. However, it’s important to understand that the condition is very responsive to preventive measures.
Although heart disease occurs primarily in individuals older than age 60, you are never too old or too young to benefit from employing the lifestyle modifications that reduce your risk. Other factors are less modifiable—hard-wired into your body—but awareness of these factors will help you understand your complete risk profile. The following discussion of the risk factors for heart disease will help you to interpret your own numbers, so you can track your progress and understand where you are—and where you need to be.
Several external and internal risk factors for heart disease have been identified. External factors include issues related to one’s environment, diet, and lifestyle. Internal risk factors include increased oxidative stress and chronic inflammation, high LDL cholesterol, the presence of small lipoprotein particles, triglycerides, low HDL cholesterol, increased homocysteine levels, and high blood pressure.
Inalterable Risk Factors
>> Age. The risk of developing heart disease increases as we age.
>> Ethnicity. African American, Hispanic, Native American, Hawaiian, and some Asian populations have a higher risk of developing heart disease than their Caucasian counterparts do.
>> Gender. Men have a higher risk of developing heart disease than women of reproductive age. Men and postmenopausal women, however, share the same risk of its development.
>> Gene defects/Family history. For a patient with heart disease, the risk increases in their children, although the genetic defects which increase risk may be transmitted to some but not all of their children.
Alterable Risk Factors
>> Chronic inflammation. This is a prolonged state that persists following injury and/or infection. It is marked by the presence of lymphocytes and macrophages, an increased number of blood vessels, fibrosis, and the death of the related tissue.
>> Diabetes. Heart disease and diabetes are the two distinct diseases with respect to target organs. Both diseases impair blood vessel activity, and some causative agents—such as obesity, physical inactivity, increased oxidative stress, and chronic inflammation—are common to both. Individuals with diabetes have a higher risk of developing heart disease than those who do not have diabetes.
>> High blood pressure. If not controlled, high blood pressure can lead to increased risk of developing heart disease and stroke.
>> High cholesterol, low LDL cholesterol, small lipoprotein particles, and high triglycerides. These abnormal lipid (fat) profiles can increase the risk of heart disease in some individuals. To understand what is meant by this, we need to know what constitutes a normal value and an abnormal one.
- In terms of total cholesterol, blood levels of 150 mg/dl or lower are considered normal, 150 to 199 mg/dl is borderline high, 200 to 249 mg/dl is high, and above 300 mg/dl is considered very high, with respect to the risk of heart disease. The higher the value of total cholesterol, the greater the risk of this disease in some individuals.
- In terms of low-density lipoprotein (LDL) cholesterol, a blood level of 100 mg/dl or lower is normal, 100 to 129 mg/dl is near normal, 130 to 159 mg/dl is borderline high, 160 to 189 mg/dl is high, and 190 mg/dl or above is very high, with respect to the risk of heart disease. The higher the level of LDL cholesterol, the greater the risk of disease in some individuals.
- In terms of high-density lipoprotein (HDL) cholesterol, a blood level of 40 mg/dl or lower is considered low and 60 mg/dl or higher is considered high. The higher the level of HDL, the lesser the risk of disease in some individuals.
- In terms of triglycerides, a blood level lower than 150 mg/dl is considered normal. The higher the value of triglycerides, the greater the risk of developing heart disease.
>> Increased homocysteine. Homocysteine is a naturally occurring substance that is produced when the amino acids methionine and cysteine are broken down. Homocysteine damages endothelial cells—cells that line the inside of blood vessels—by generating excessive amounts of free radicals. Risk associated with homocysteine is independent of abnormal changes in lipid profiles; homocysteine can damage the endothelial cells lining the blood vessels that supply blood to the heart. This means that increased homocysteine may increase the risk of heart disease even in the presence of normal lipid profiles.
>> Increased C-reactive protein (CRP) levels. CRP is one of the protein markers of inflammation present in the blood; it is elevated in heart disease. Increased levels of CRP can cause damage to endothelial cells and, thus, can increase the risk of developing heart disease.
>> Obesity. It is now established that obesity markedly increases one’s risk of developing heart disease.
>> Oxidative stress. This is a condition in which an increased production of free radicals derived from oxygen and nitrogen occurs. It has been determined that oxidative stress is a contributing factor to heart disease.
>> Physical inactivity. Those who perform very little physical activity have a higher risk of developing disease than those who are active.
>> Plaque. The presence of plaque in the arteries makes them stiff, causing a progressive narrowing of them, which can reduce or even stop the blood supply. This contributes to an elevated risk of heart disease.
>> Smoking tobacco. Smoking is one of the major lifestyle-related factors that increases the risk of developing heart disease in both men and women.
Taking a Closer Look
Whether modifiable or unmodifiable, some of the aforementioned risk factors merit further explanation. Let’s take a deeper look at these.
An increased production of free radicals contributes to the aging process. Mitochondria are the energy plants of each cell and are abundant in hard muscle cells. Free radicals are a normal by-product of energy creation, but unfortunately, mitochondria are very vulnerable to the damage produced by them. Damaged mitochondria consequently produce more free radicals and less energy, which increases the risk of heart disease.
As we age, a loss of muscle mass occurs. One of the reasons for this is that oxidized proteins (damaged by free radicals) are not removed from the body. Proteasomes, complex enzyme systems present in all cells, clear away damaged proteins. As the body ages, the increased burden of free radicals damages them and compromises their function. Proteasome damage results in accumulation of oxidized proteins, which eventually kill mitochondria cells.
Telomeres are the endcaps of chromosomes; they protect them from deterioration. As we age, the length of telomeres gradually decreases, and increased oxidative stress causes the telomeres to shorten more quickly. Although dietary antioxidants, such as vitamins C and E, reduce the rate of telomere shortening, the effectiveness of these and other supplements, like glutathione and CoQ10, decreases as we age. The reduced potency of these antioxidants serves to increase the levels of oxidative stress in the body.
Even though we have demonstrated the effects of aging on the development of heart disease, we should also know that recent scientific studies suggest that younger people are showing earlier signs of heart disease. There is increased incidence of obesity and physical inactivity in this demographic, which is why it’s important for young people to start getting healthy now rather than wait until disease sets in.
Cholesterol plays a major part in the initiation and progression of heart disease, yet about 50 percent of the patients who are hospitalized with heart attack symptoms have normal cholesterol levels. Nevertheless, improving cholesterol profiles is considered one of the more effective strategies to reduce the risk of developing heart disease.
Cholesterols are either formed from dietary fats or made in the liver. Triglycerides and cholesterols formed from both sources then combine with proteins to form lipid-protein complexes, or lipoproteins. These lipoproteins vary in their lipid and protein content, and they contain cholesterols which can be very-low-density lipids (VLDLs), low-density lipids (LDLs), or high-density lipids (HDLs).
In the blood, VLDLs are converted to LDLs by the action of lipoprotein lipase enzymes. LDLs are the carriers of cholesterols to the various tissues in the body. HDLs consist of lipids and proteins of different sizes that are formed in the liver and small intestine.
In the early stages of its formation, HDL lacks cholesterol, but it soon acquires it in the peripheral tissues. One of the major functions of HDL is to transport acquired cholesterols back to the liver where they’re converted to bile acids, which are then stored in the gall bladder. In addition to apoproteins, HDL can contain many enzymes, including the antioxidant enzyme glutathione peroxidase. HDL exhibits antioxidant and anti-inflammatory activities, which is why we commonly refer to it as “good” cholesterol—and to LDL as “bad” cholesterol.
Let’s examine the role that a family history of heart disease may play in its development. If the gene defects of the heart disease pass from one generation to another, the development of heart disease in a child can be attributed to a family history of the disease.
However, pinpointing whether family history or lifestyle choices actually cause the disease is often murky. Suppose that one or both parents were smokers or had other risks factors for developing heart disease and died of heart attack at the age of 70 or older. Is their children’s risk of developing heart disease genetically predetermined? The answer is no. Generally, individuals who derive from a family with a history of heart disease are not impacted by the lifestyle and dietary choices that their forebearers made.
Children are at increased risk of developing heart disease at a younger age if their parents died young (younger than the age of 50) from the disease. In both men and women, family history of heart disease is a strong and independent risk factor for its development. The inherited gene defects interact with other heart-disease risk factors in a synergistic manner. Therefore, individuals with a family history of heart disease should make sure to make wise and prudent choices in regard to lifestyle and diet.
Studies connecting the development of heart disease to obesity are predominantly mouse-based. In many studies, a high-fat diet increased the levels of pro-inflammatory cytokines in mice. These pro-inflammatory cytokines play a primary role in the initiation and progression of atherosclerosis (arterial plaque buildup) and heart disease. In some studies, an infusion of the insulin-like growth factor-1 (IGF-1) decreased levels of these cytokines and markers of oxidative damage, as well as the progression of atherosclerosis and plaque. Mice fed with a high-fat, high-sugar diet displayed the progressive increase in the size of their left ventricle, which causes a reduced pumping of blood.
These animals also had an increased level of plasma glucose and showed insulin resistance. Treatment with resveratrol, an antioxidant isolated from grape seeds or skins, prevented damage to the heart in these mice. It was found that obesity also increased the risk of atrial fibrillation by dilating the left atrial. This effect of obesity is due primarily to an increased production of free radicals.
Plaque is a fat-like substance found in the walls of veins and arteries in the body. It is thought that plaque, particularly unstable plaque, plays a central role in precipitating heart attacks and strokes.
Plaque buildup may cause narrowing of the coronary arteries that supply blood to the heart. If these vital arteries are injured, platelet aggregation may occur within the wall of the artery adjacent to the plaque. However, if the plaque ruptures, a blood clot can form on the surface of the artery. Depending on the size of the clot, blood flow to the heart can be partially or fully blocked. Sometimes clots may also break free, causing a blockage of the blood supply to distant organs such as the brain—which can cause a stroke. Clots can also block the blood vessels to the lungs, which may lead to death.
It is important to understand how plaque is formed. Oxidized (or damaged) LDL cholesterol may be one of the earliest events initiating plaque formation. It does this in several ways: by enhancing platelet adhesion and aggregation, by impairing the elasticity of the coronary arteries, and by increasing the formation of foam cells, which form when oxidized LDL cholesterol is engulfed by macrophages. C-reactive protein increases the uptake of oxidized LDL cholesterols by macrophages, thereby increasing the number of foam cells.
Oxidized LDL cholesterol can also increase the proliferation of vascular smooth muscles—and both foam cells and vascular smooth muscle cells contribute to the formation of plaque in coronary arteries. Once plaque is formed, it serves as a continuous stimulus for increased inflammatory reactions that release reactive oxygen species and pro-inflammatory cytokines, all of which are toxic to heart cells.
Thus, we see how an increase in oxidative stress contributes to atherosclerosis. Studies suggest that preventing the oxidation of LDL cholesterol should reduce the risk of developing plaque and atherosclerosis.
As mentioned, endothelial cells line the walls of the blood vessels that supply blood to the heart and can be damaged by free radicals or by-products that are released from chronic inflammatory reactions and homocysteine. It is now recognized that endothelial cell dysfunction may be one of the early events in the development of heart disease. Damaged endothelial cells may reduce the activity of nitric oxide synthase, an enzyme responsible for making nitric oxide (NO). Because NO regulates the dilation of blood vessels, a reduction in NO (by way of reduced nitric oxide synthase) will reduce the dilation of blood vessels.
It should be noted that excessive production of NO may also be harmful. This is because the oxidation of NO forms peroxynitrite, a form of free radical that can cause damage to the arteries, causing dysfunction. Thus, in order to maintain the normal functioning of blood vessels, it is essential to maintain the proper levels of NO in the body. Both deficiency and excess production of NO can impair blood-vessel activity. Therefore, protecting endothelial cells against free radical damage and preventing the formation of plaque may be considered useful strategies in reducing the risk of developing heart disease.
Tobacco smoking increases the level of NO in the body and generates other forms of free radicals. It also depletes antioxidant levels in the body. Smoking tobacco is also associated with increased blood concentration of CRP in men and women. It was found that the CRP levels of all the men and women who had quit smoking returned to normal after several years of abstinence from tobacco.
Family history is a significant factor that one cannot influence. If a male in your immediate family has had a heart attack before the age of 55 or if a female in your family has had one before the age of 65, you are at greater risk of developing heart disease yourself. But even if you have a family history of heart disease—and especially if this is so—risk can be mitigated through other factors that can be controlled.
These risk factors include obesity, physical inactivity, high blood pressure, high LDL cholesterol, smoking tobacco, drug abuse, increased oxidative stress, chronic inflammation, and elevated homocysteine levels. These factors may all be influenced through the incorporation of moderate exercise into your daily routine, mindfulness of the fat and salt content of food, and making necessary, but sensible, adjustments to bring your weight down, should you be overweight or obese.
By Kedar N. Prasad, PhD