Endothelial dysfunction predicts early-stage cardiovascular disease

Global Impact

Cardiovascular disease (CVD), also known as heart disease, is a broad term used to describe a range of diseases that involve the heart, blood vessels or both. Often CVD refers to conditions related to atherosclerosis (arterial disease), when occurs when the walls of your arteries thicken from the accumulation of fatty materials such as cholesterol. Over the years, the medical community has discovered a number of risk factors from which they have developed new strategies to effectively treat and prevent CVD. Despite these gains, CVD remains the leading cause of death globally, accounting for nearly 17 million deaths in 2011 1.

Endothelial Dysfunction

WHAT CAUSES CVD?

According to the National Institutes of Health3, there are five primary factors that contribute to damage to the lining and inner layers of the arteries. These primary risk factors include:

  • Unhealthy Blood Cholesterol Level.This includes high LDL cholesterol (sometimes called "bad" cholesterol) and low HDL cholesterol (sometimes called "good" cholesterol).
  • High Blood Pressure.Blood pressure is considered high if it stays at or above 140/90 mmHg over time. If you have diabetes or chronic kidney disease, high blood pressure is defined as 130/80 mmHg or higher. (The mmHg is millimeters of mercury—the units used to measure blood pressure.)
  • SmokingSmoking can damage and tighten blood vessels, raise cholesterol levels, and raise blood pressure. Smoking also doesn't allow enough oxygen to reach the body's tissues.
  • Insulin ResistanceThis condition occurs if the body can't use its insulin properly. Insulin is a hormone that helps move blood sugar into cells where it's used as an energy source. Insulin resistance may lead to diabetes.
  • Diabetes.With this disease, the body's blood sugar level is too high because the body doesn't make enough insulin or doesn't use its insulin properly.
  • Unhealthy Weight or Obesity The terms "overweight" and "obesity" refer to body weight that's greater than what is considered healthy for a certain height.
  • Lack of Physical Activity.A lack of physical activity can worsen other risk factors for atherosclerosis, such as unhealthy blood cholesterol levels, high blood pressure, diabetes, and overweight and obesity.
  • Unhealthy Diet.An unhealthy diet can raise your risk for atherosclerosis. Foods that are high in saturated and trans fats, cholesterol, sodium (salt), and sugar can worsen other atherosclerosis risk factors.
  • Older Age.As you get older, your risk for atherosclerosis increases. Genetic or lifestyle factors cause plaque to build up in your arteries as you age. By the time you're middle-aged or older, enough plaque has built up to cause signs or symptoms. In men, the risk increases after age 45. In women, the risk increases after age 55.
  • Family History of Early Heart Disease.Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease before 55 years of age, or if your mother or a sister was diagnosed with heart disease before 65 years of age.

Accumulation of plaque occurs where the arteries are damaged and over time, plaque may harden or rupture. Platelets clump to the site of the injury and may form blood clots. Plaque build-up and blood clots narrow the arteries and restrict blood flow, reducing the availability of oxygen-carrying red blood cells. A complete blockage may lead to a heart attack or stroke.

Learn more about causes and conditions related to cardiovascular disease on the American Heart Association interactive website here

Types & Stages of CVD

Cardiovascular disease affects your heart and your blood vessels. Damage to your heart can begin early without any signs or symptoms. Much of this early damage occurs to your endothelium, the single-cell-layer that lines all the blood vessels in your body. As a result, there are many related diseases and conditions that can result from poor management of CVD risk factors. These conditions and diseases are summarized in Table 1 below.

Table 1. Cardiovascular and Related Diseases and Conditions

 Name Description Prevalence
 Coronary Artery Disease
Caused by plaque build-up in the arteries of the heart. Leads to heart attacks. 1 in 2 males over 40, 1 in 3 females over 405
 Cardiomyopathy
Disease of heart muscle that results in abnormal cardiac function 1 in 100 people6
 Heart Failure
Occurs when the heart is unable to provide sufficient pump action to maintain blood flow.  1 in 50 people7
 Pulmonary Heart Disease
Enlargement and failure of the right ventricle due to high blood pressure.  1 in 1000 people8
 Vascular Dementia
Caused by problems with blood supply to the brain, typically manifested via a series of strokes.  1 in 150 people9
 Cardiac dysrythmias
Abnormalities of heart rhythm, including atrial fibrillation.  Up to 1 in 100 people10
 Cerebrovascular Disease 
A group of brain dysfunctions that occur when blood vessels supplying the brain are damages. May lead to stokes.  1 in 40 people have had a stroke11
 Peripheral Arterial Disease
Obstruction of large arteries in the arms or legs that may cut off blood supply.  1 in 20 people over 4012
 Congenital Heart Disease
The most common birth defect, affects the structure of the heart and great vessels.  1 in 100 births13

 One of the first stages of cardiovascular disease is damage to your endothelium, which is the single-cell-thick interior lining of all blood vessels in your body. In fact, your level of endothelial dysfunction can predict the occurrence of CVD years in advance, even you do not currently exhibit any symptoms. This is because inflammation leads to thickening of the blood vessels, resulting in a measurable reduction of arterial elasticity during the early stages of CVD. The progression of endothelial damage is illustrated below, including descriptions of the various complications that stem from each stage of this condition.

Screening Procedures

Several steps are required to create a comprehensive cardiovascular disease risk assessment. First, a documentation of your history (i.e. age, family history, smoking status, etc.) is performed followed by a physical examination (BMI, waist measurement). Next, laboratory tests such as fasting plasma glucose, creatinine, and fasting lipid profile are performed. The latter blood test produces total cholesterol, HDL, LDL, and triglycerides measurements.Additional tests may include an exercise stress test (EST), imagining techniques like computed tomography (CT) and magnetic resonance imaging (MRI). To quantify total risk, healthcare providers may use the North American Framingham Risk Score (FRS) or European SCORE Risk Charts to account for effects like metabolic syndrome. Recently providers have been incorporating techniques that quantify endothelial dysfunction (EDF) as well. Table 2 below summarizes common laboratory tests that do not involve getting your blood drawn.

 Test Description
 European SCORE Risk Charts  Based on a large data set tested thouroughly on European populations calibrated to each country's mortality
 Framingham Risk Score  Based on data obtained form the Framingham Heart Study, used to estimate 10-year CVD risk
 Exercise Stress Test  Measures the heart's ability to respond to external stress in a controlled clinical envrionment
Computed Tomography & Magnetic Resonance Imaging Medical imaging procedures that are used to visualize internal structures if the body
Quantifying Endothelial Dysfuction Measures disruption of vascular homeostasis that leads to atherosclerosis


Prevention and Treatment

There are two types of prevention: primary and secondary. Primary prevention aims to slow or stop the onset of cardiovascular disease before a serious event occurs. Secondary prevention aims to prevent a repeat cardiac event, so that your cardiovascular disease does not get worse.
Treatment may refer to drugs, minimally invasive procedures, or surgery for when cardiovascular disease has already developed to stage when behavioral changes are not enough. Here are a few options for primary and secondary preventions that positively affect your endothelial function and lower your risk of developing CVD or experiencing another CVD event:CVD Risk Factor TableOn the other hand, several minimally invasive procedures have been developed that may provide relief from symptoms of cardiovascular disease, including angioplasty and stenting, which can be used to treat blockages. Surgical solutions may involve bypass surgery, where arteries or veins are grafted to the coronary arteries to improve blood supply.
Learn more about risk screening and ways to prevent CVD from the AHA here.

References

  1. http://www.who.int/mediacentre/factsheets/fs317/en/index.html
  2. Michael E. Widlansky, MD et al. The Clinical Implications of Endothelial Dysfunction. Journal of the American College of Cardiology Vol. 42, No. 7, 2003. http://www.ncbi.nlm.nih.gov/pubmed/14522472.
  3. http://www.nhlbi.nih.gov/health/health-topics/topics/hdw/causes.html
  4. National Heart Lung and Blood Institute. 2013.
  5. Rosamond W, Flegal K, Friday G (February 2007). "Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee". Circulation 115 (5): e69–171.
  6. https://www.clinicalkey.com/
  7. Bui, AL; Horwich, TB; Fonarow, GC (January 2011). "Epidemiology and risk profile of heart failure.". Nature Reviews Cardiology 8 (1): 30–41.
  8. http://www.pulmonaryheartdisease.net/
  9. Plassman, B.L.; Langa, K. M.; Fisher, G. G.; Heeringa, S. G.; Weir, D. R.; Ofstedal, M. B.; Burke, J.R.; Hurd, M. D.; Potter, G. G.; Rodgers, W. L.; Steffens, D. C.; Willis, R. J.; Wallace, R. B. (2007). "Prevalence of dementia in the United States: The aging, demographics, and memory study.". Neuroepidemiology 29 (1-2): 125–132.
  10. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/atrial- fibrillation/
  11. http://www.cdc.gov/nchs/fastats/stroke.htm
  12. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_pad.htm
  13. http://www.cdc.gov/ncbddd/heartdefects/data.html

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