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Understanding Cardiovascular Biomarkers

“Nothing can compare with the activity of the human heart.”
—Denton A. Cooley

Despite considerable advances in the treatment of cardiovascular (heart) disease, it remains the leading cause of death in the United States. Diabetes, particularly Type 2 diabetes, is a major risk factor for cardiovascular disease. In fact, the rate of death from heart disease is two to four times higher in adults with diabetes than in their counterparts without diabetes.

Several factors are known to increase the risk of developing (and dying from) heart disease, including being male, using any form of tobacco, and having higher total and LDL (low-density lipoprotein, or “bad”) cholesterol levels and higher blood pressure. While your health-care provider will most certainly monitor and possibly treat these “classic” risk factors for cardiovascular disease, he may also monitor other biological markers to get a broader picture of what is happening to your heart and blood vessels. While these additional measurements are not as well-researched or closely associated with developing or dying from heart disease, they may provide information that is valuable in certain situations, such as when classic risk factors give mixed or unclear results. This article describes some of the more common tests that may be prescribed to get more information about your cardiovascular risk.

Cardiovascular biomarkers
The National Institutes of Health (NIH) describes a biological marker, or biomarker, as a characteristic that is an indicator of normal body processes, disease-related processes, or responses to a therapeutic intervention. The relationship of any such measurement to health or disease is established through scientific studies involving both healthy and sick individuals. It is thus possible that any of the biomarkers discussed in this article could gain or lose importance in the future, as research on the topic progresses.

Cardiovascular biomarkers may help determine someone’s potential for cardiovascular disease early on, before any classic signs and symptoms of the disease occur. Experts are still trying to determine whether early treatment of cardiovascular disease based on cardiovascular biomarkers is useful in preventing or delaying its onset. Some of the more commonly used cardiovascular biomarkers are high-sensitivity C-reactive protein, B-type natriuretic peptide, albumin-to-creatinine ratio, plasminogen activator inhibitor-1, and adiponectin.

High-sensitivity C-reactive protein. This marker of inflammation may indicate the presence of atherosclerosis, a fatty buildup in the arteries. Of all the biomarkers discussed in this article, the evidence connecting high-sensitivity C-reactive protein at elevated levels to heart disease and future cardiovascular events (such as a heart attack or stroke) is greatest. High-sensitivity C-reactive protein is often elevated in people with diabetes, who are known to have a higher risk of developing cardiovascular disease.

B-type natriuretic peptide. This biomarker is used to help detect and determine the severity of congestive heart failure. When the heart muscle begins to enlarge — which happens, in the case of heart failure, as the muscle tries to respond to its inability to pump blood adequately throughout the body — this substance is secreted into the blood. The amount of B-type natriuretic peptide in the blood therefore tends to correspond to the risk of heart failure. Some studies have suggested that decreases in this biomarker can be beneficial.

Albumin-to-creatinine ratio. This biomarker describes the ratio, or balance, between two substances, creatinine and albumin, that are both waste products normally found in urine. Test results are reported as milligrams (mg) of albumin per gram (g) of creatinine. Studies have suggested that this ratio is an independent risk factor for cardiovascular disease, especially in people with diabetes or hypertension (high blood pressure). It is more commonly used, however, to screen for kidney disease, as increased albumin in the urine is often an early sign of reduced kidney function.

Plasminogen activator inhibitor-1. This biomarker, a protein, is associated with thrombosis, or clotting of the blood. It can increase when you have an infection, certain kinds of inflammation, or an injury. Low levels of it may make a person susceptible to bleeding disorders. In people with diabetes, particularly those who are obese, plasminogen activator inhibitor-1 levels are commonly elevated, which is associated with a higher risk of cardiovascular disease. It is believed that this protein plays a role in the development of atherosclerosis (“hardening of the arteries”), in which fatty deposits build up in the arteries and restrict blood flow.

Adiponectin. This hormone helps control blood glucose levels and the breakdown of fats in the body. Although scientists are not exactly sure why, reduced levels of adinopenectin are associated with various “classic” risk factors for cardiovascular disease such as Type 2 diabetes, obesity, and atherosclerosis.

It is important to note that only a few cardiovascular biomarker tests are routinely used at present, and not by all health-care providers. However, since these tests may yield evidence of cardiovascular risk before classic risk factors are present, they may be useful for people with diabetes, due to their already elevated risk of cardiovascular disease. Your health-care provider will likely decide whether or not to test certain biomarkers based on your risk for cardiovascular disease as determined by classic risk factors, as well as based on his experience with the usefulness of testing.

Interpreting your results
When you have any type of laboratory test performed, it is important that you understand what the results mean for you. When your lab tests are reported to your health-care provider, he will usually compare the result with a reference range that is supplied as part of the laboratory analysis (see “Cardiovascular Biomarker Tests”). The term “reference” is preferred to “normal” because normal is often difficult to define. A reference range is based on the numbers typically seen within a group of healthy individuals. If appropriate for a particular lab test, the reference range will take your age and sex into consideration.

Your health-care provider will evaluate your results within the full context of your medical status. In doing so, he may take several things into account, depending on the specific test. These additional considerations may include any medicines, vitamins, or herbal remedies you’re taking; your caffeine intake; any tobacco or alcohol use; your dietary preferences (such as whether you are a vegetarian); and your stress or anxiety level. Exercise and physical activity can also alter some enzyme and hormone levels. Pregnancy can affect a woman’s laboratory values; for many tests, in fact, there is a separate reference range for pregnant women. Because your test results may be affected by various lifestyle choices or personal characteristics, it is important that you accurately and completely answer any questions your health-care provider has about behaviors that may affect how test results are interpreted.

When your health-care provider evaluates the results of your tests, he will note not only whether your results fall within a particular reference range, but also any changes in your results since you last had the test done (if, in fact, you have had it done before). An improvement in your results — even if the number is not yet within the reference range — may suggest that a treatment or strategy is working, while no improvement may indicate that a change in treatment is necessary.

Classic CVD risk factors
As mentioned earlier, the biomarkers at the focus of this article are distinct from the classic risk factors for cardiovascular disease. Like Type 2 diabetes, cardiovascular disease tends to run in families. Nevertheless, many risk factors can be prevented or minimized. This includes, to some extent, diabetes, since poor blood glucose control is associated with greater cardiovascular risk. High blood glucose levels can damage blood vessels, contributing to atherosclerosis and reduced blood flow to the heart, brain, and limbs.

Chronic high blood pressure affects the majority of people with diabetes. High blood pressure is a major risk factor for atherosclerosis and heart disease, and it can also contribute to other blood vessel problems related to diabetes, such as retinopathy (eye disease) and nephropathy (kidney disease).

Having high triglycerides, high total cholesterol, high LDL cholesterol, or low HDL (high-density lipoprotein, or “good”) cholesterol raises the risk of heart disease. Cholesterol and triglycerides are collectively called blood lipids, and any combination of abnormal lipid levels is called dyslipidemia. People with Type 2 diabetes often have high triglycerides, low HDL cholesterol, and a high level of small, dense LDL cholesterol particles, which are even more harmful than normal LDL cholesterol particles. Being overweight, especially when you carry your weight around your abdomen, is associated with an increase in the body’s production of LDL cholesterol.

Smoking cigarettes doubles your risk of developing heart disease. Smoking leads to the narrowing of the blood vessels and deprives them of oxygen, a vital substance in the circulatory system.

The classic risk factors for heart disease can usually be addressed through lifestyle changes, including choosing healthier foods, controlling portion sizes, and getting regular physical activity. Depending on your health-care provider’s assessment of your level of risk, you may also need one or more drugs to treat each risk factor. If you are a smoker or use tobacco in any other form, talk with your health-care provider about resources to help you quit. (For more tips on preventing CVD, click here.)

Love your heart
When you have diabetes, you are at higher risk for heart disease. This doesn’t mean, however, that it’s inevitable. The more information you have about your heart and cardiovascular system, the more informed the choices that you and your health-care provider make will be. By paying close attention to the classic cardiovascular risk factors, and supplementing these results with cardiovascular biomarker tests when appropriate, you and your provider will be making the most of the options available. Do all that you can out of love for your heart. It needs you, and you most definitely need it!



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