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Introduction to the Cardiovascular System

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Introduction to the Cardiovascular System

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My text set is on the cardiovascular system of the human body. This set will go over the functions, anatomy and processes of this system. This text set can be given to students or anyone who wants to learn more about the cardiovascular system.

Science --> Human Anatomy

Grades --> 11th and 12th

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The cardiovascular system is consisted of the heart, arteries, veins and capillaries. This system transports blood throughout the body and helps maintain homeostasis.

Link --> Website https://training.seer.cancer.gov/anatomy/cardiovascular/

Genre --> Science

Readability Level --> Proficient

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Introduction to the Cardiovascular System

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The cardiovascular system is sometimes called the blood- vascular, or simply the circulatory, system. It consists of the heart, which is a muscular pumping device, and a closed system of vessels called arteries, veins, and capillaries.

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In the image above is a label diagram of the different structures of the heart. The main structures are for example the right atrium, left atrium, superior vena cava and the aorta.

Source --> Picture

Genre --> Science

Readability Level --> Basic

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The heart plays a vital function on keeping us alive. We could not get oxygen into our body without the heart.

Link --> Video https://www.youtube.com/watch?v=X9ZZ6tcxArI

Genre --> Science

Readability Level --> N/A

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The Heart, Part 1 - Under Pressure: Crash Course Anatomy & Physiology #25

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In contrast, preliminary results from the Feasibility Trial of the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes found an increased risk of cardiovascular events in insulin-treated patients with NIDDM. Fur- ther studies are needed to determine the role of insu- lin in the risk of cardiovascular disease.

Link --> Case Study http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.601.2380&rep=rep1&type=pdf

Genre --> Science

Readability Level --> Advanced

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The ECG is the full cycle of one heart beat. There are P waves, Q waves, R waves, S waves and T waves. Each of these waves are different electrical stimuli coming from the heart.

Link --> Video https://www.youtube.com/watch?v=FThXJUFWUrw

Genre --> Science

Readability Level --> N/A

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EKG/ECG Interpretation (Basic) : Easy and Simple!

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Blood pumps through the heart in to cycles. The first pump happens in the atriums. This pump pushes blood into the ventricles. The second pump happens in the ventricles. This pump pushes blood to either the lungs or the rest of the body.

Link --> Website https://www.webmd.com/heart-disease/guide/how-heart-works

Genre --> Science

Readability Level --> Proficient

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How the Heart Works & Pumps Blood Through The Human Body

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The human heart is an amazing organ. Learn how it works to pump blood throughout the human body using electrical signals from the brain from the experts at WebMD.

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It is therefore the aim of the current cross-sectional study to assess the overall and gender-specific prevalence of the metabolic syndrome and its components in a cohort of patients with different clinical manifestations of atherosclerotic vascular disease.

Link --> Case Study https://www.sciencedirect.com/science/article/pii/S0021915004000292?casa_token=rcKvx0HOy1UAAAAA:sUulmQbLi7q4LaF47KVanB32f7DuCrggrbkcqGZDfPscJOzgqbV_KZcBGlY7g1tVZNbVhFZUxg

Genre --> Science

Readability Level --> Advanced

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Abstract

Metabolic syndrome patients are at increased risk for developing cardiovascular morbidity and mortality. The increasing prevalence of the metabolic syndrome in various asymptomatic populations has been well documented, however, limited information is available about the prevalence in manifest atherosclerotic vascular disease patients. The aim of this study is to determine the overall and gender-specific prevalence of the metabolic syndrome and its components in these patients. This cross-sectional survey of 1117 patients, aged 18-80 years, mean age 60±10 years, comprised patients with coronary heart disease ( n=527), cerebrovascular disease ( n=258), peripheral arterial disease ( n=232) or abdominal aortic aneurysm ( n=100). Metabolic syndrome was defined by Adult Treatment Panel III. The prevalence of the metabolic syndrome in the study population was 46%: 58% in PAD patients, 41% in CHD patients, 43% in CVD patients and 47% in AAA patients. Overall, women had a higher prevalence than men (56% versus 43%). Age did not influence the metabolic syndrome prevalence; crude odds ratios (crude OR) 1.00 (95% CI: 0.99-1.02). Our results demonstrate a high prevalence of the metabolic syndrome in patients with manifest atherosclerotic vascular disease. Screening for metabolic syndrome in patients with high risk for new vascular incidents may identify patients with even higher vascular risk and may direct anti-atherosclerotic treatment in order to prevent new vascular incidents in the same or another vascular bed.

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Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm

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Metabolic syndrome patients are at increased risk for developing cardiovascular morbidity and mortality. The increasing prevalence of the metabolic syndrome in various asymptomatic populations has been well documented, however, limited information is available about the prevalence in manifest atherosclerotic vascular disease patients.

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Capillaries are the section of blood vessels that gas exchange happens. Oxygen is either received or released inside the capillaries.

Link --> Website https://www.healthline.com/health/function-of-capillaries

Genre --> Science

Readability Level --> Proficient

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Capillaries are very tiny blood vessels - so small that a single red blood cell can barely fit through them.

They help to connect your arteries and veins in addition to facilitating the exchange of certain elements between your blood and tissues.

This is why tissues that are very active, such as your muscles, liver, and kidneys, have an abundance of capillaries. Less metabolically active tissues, such as certain types of connective tissue, don't have as many.

Read on to learn more about the function of capillaries and the conditions that can affect them.

Capillaries connect the arterial system - which includes the blood vessels that carry blood away from your heart - to your venous system. Your venous system includes the blood vessels that carry blood back to your heart.

The exchange of oxygen, nutrients, and waste between your blood and tissues also happens in your capillaries. This happens through two processes:

Passive diffusion. This is the movement of a substance from an area of higher concentration to an area of lower concentration.

Pinocytosis. This refers to the process through which your body's cells actively take in small molecules, such as fats and proteins.

The walls of capillaries are made up of a thin cell layer called endothelium that's surrounded by another thin layer called a basement membrane.

Their single-layer endothelium composition, which varies among the different types of capillaries, and surrounding basement membrane makes capillaries a bit "leakier" than other types of blood vessels. This allows oxygen and other molecules to reach your body's cells with greater ease.

Additionally, white blood cells from your immune system can use capillaries to reach sites of infection or other inflammatory damage.

There are three types of capillaries. Each has a slightly different structure that allows to function in a unique way.

Continuous capillaries

These are the most common types of capillaries. They contain small gaps in between their endothelial cells that allow for things like gases, water, sugar (glucose), and some hormones to pass through.

The continuous capillaries in the brain are an exception, however.

These capillaries are part of the blood-brain barrier, which helps to protect your brain by only allowing the most essential nutrients to cross.

That's why the continuous capillaries in this area don't have any gaps between endothelial cells, and their surrounding basement membrane is also thicker.

Fenestrated capillaries

Fenestrated capillaries are "leakier" than continuous capillaries. They contain small pores, in addition to small gaps between cells, in their walls that allow for the exchange of larger molecules.

This type of capillary is found in areas that require a lot of exchange between your blood and tissues. Examples of these areas include:

the small intestine, where nutrients are absorbed from food

the kidneys, where waste products are filtered out of the blood

Sinusoid capillaries

These are the rarest and "leakiest" type of capillary. Sinusoid capillaries allow for the exchange of large molecules, even cells. They're able to do this because they have many larger gaps in their capillary wall, in addition to pores and small gaps. The surrounding basement membrane is also incomplete with openings in many places.

These types of capillaries are found in certain tissues, including those of your liver, spleen, and bone marrow.

For example, in your bone marrow, these capillaries allow newly produced blood cells to enter into the bloodstream and begin circulation.

While capillaries are very small, anything unusual in their functioning can cause visible symptoms or even potentially serious medical conditions.

Port wine stains

Port wine stains are a type of birthmark caused by the widening of capillaries located in your skin. This widening causes the skin to appear pink or dark red in color, giving the condition its name. Over time, they can darken in color and thicken.

While they don't go away on their own, port wine stains also don't spread to other areas.

Port wine stains typically don't require treatment, although laser treatment can help to make them lighter in color.

Petechiae

Petechiae are small, round spots that appear on the skin. They're typically about the size of a pinhead, can be red or purple in color, and are flat in the skin. They happen when capillaries leak blood into the skin. They don't lighten in color when pressure is applied over them.

Petechiae are typically a symptom of an underlying condition, including:

Some medications, including penicillin, can also cause petechiae as a side effect.

Systemic capillary leak syndrome

Systemic capillary leak syndrome (SCLS) is a rare condition that doesn't have a clear cause. But experts think it may be related to a substance in the blood that damages capillary walls.

People with SCLS have recurring attacks during which their blood pressure drops very quickly. These attacks can be severe and require emergency medical attention.

These attacks are usually accompanied by some initial warning signs, including:

nasal congestion

cough

nausea

headache

abdominal pain

lightheadedness

swelling in arms and legs

fainting

SCLS is usually treated with medications that help to prevent these attacks from occurring.

Arteriovenous malformation syndrome

People with arteriovenous malformation syndrome (AVM) have an abnormal tangle of arteries and veins that are connected to each other without capillaries in between. These tangles can occur anywhere in the body, but are most often found in the brain and spinal cord.

This can cause lesions that interfere with blood flow and oxygen delivery. These lesions may also cause bleeding into the surrounding tissue.

AVM usually doesn't cause symptoms, so it's usually only discovered while trying to diagnose another condition. However, in some cases, it can cause:

headaches

pain

weakness

issues with vision, speech, or movement

seizures

AVM is a rare condition that's often present at the time of birth. Treatment usually involves surgically removing or closing the AVM lesion. Medication can also help to manage symptoms, such as pain or headaches.

Microcephaly-capillary malformation syndrome

Microcephaly-capillary malformation syndrome is a rare genetic condition that starts before birth.

People with this condition have smaller heads and brains. They also have widened capillaries that increase the flow of blood near the skin surface, which can cause pinkish red spots on the skin.

Additional symptoms can include:

severe developmental delays

seizures

difficulty eating

unusual movements

distinct facial features, which can include a sloped forehead, round face, and unusual hair growth

slower growth

shorter or smaller stature

finger and toe abnormalities, including really small or absent nails

Microcephaly-capillary malformation syndrome is caused by a mutation in a specific gene called the STAMBP gene. Mutations to this gene can result in cells dying during development, affecting the entire development process.

Treatment for this condition can involve stimulation - particularly through sound and touch - bracing to maintain posture, and anticonvulsant medication therapy for management of seizures.

Capillaries are tiny blood vessels that play a big role in facilitating the exchange of various substances between your bloodstream and tissues. There are several types of capillaries, each with a slightly different structure and function.

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Function of Capillaries: Definition, Structure, Types, and Conditions

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Capillaries are very tiny blood vessels - so small that a single red blood cell can barely fit through them. They help to connect your arteries and veins in addition to facilitating the exchange of certain elements between your blood and tissues.

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Veins carry deoxygenated blood through the body back to the heart. The blood moves through the veins toward the heart. Veins come after venules that are after the capillaries.

Link --> Website https://www.healthline.com/health/venous-system#venous-system-diagram

Genre --> Science

Readability Level --> Proficient

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What is the venous system?

Veins are a type of blood vessel that return deoxygenated blood from your organs back to your heart. These are different from your arteries, which deliver oxygenated blood from your heart to the rest of your body.

Deoxygenated blood that flows into your veins is collected within tiny blood vessels called capillaries. Capillaries are the smallest blood vessels in your body. Oxygen passes through the walls of your capillaries to your tissues. Carbon dioxide can also move into your capillaries from the tissue before entering your veins.

The venous system refers to the network of veins that work to deliver deoxygenated blood back to your heart.

The walls of your veins are made up of three different layers:

Tunica externa. This is the outer layer of the vein wall, and it's also the thickest. It's mostly made up of connective tissue. The tunica externa also contains tiny blood vessels called vasa vasorum that supply blood to the walls of your veins.

Tunica media. The tunica media is the middle layer. It's thin and contains a large amount of collagen. Collagen is one of the main components of connective tissue.

Tunica intima. This is the innermost layer. It's a single layer of endothelium cells and some connective tissue. This layer sometimes contains one-way valves, especially in the veins of your arms and legs. These valves prevent blood from flowing backward.

Veins are often categorized based on their location and any unique features or functions.

Pulmonary and systemic veins

Your body circulates blood on two different tracks called the systemic circuit and the pulmonary circuit. Veins are based on the circuit they're found in:

Pulmonary veins. The pulmonary circuit carries deoxygenated blood from your heart to your lungs. Once your lungs oxygenate the blood, the pulmonary circuit brings it back to your heart. There are four pulmonary veins. They're unique because they carry oxygenated blood. All other veins carry only deoxygenated blood.

Systemic veins. The systemic circuit carries deoxygenated blood from the rest of the body back to your heart, where it then enters the pulmonary circuit for oxygen. Most veins are systemic veins.

Deep veins and superficial veins

Systemic veins are further classified as being either:

Deep veins. These are found in muscles or along bones. The tunica intima of a deep vein usually has a one-way valve to prevent blood from flowing backward. Nearby muscles also compress the deep vein to keep blood moving forward.

Superficial veins. These are located in the fatty layer under your skin. The tunica intima of a superficial vein can also have a one-way valve. However, without a nearby muscle for compression, they tend to move blood more slowly than deep veins do.

Connecting veins. Blood from superficial veins is often directed into the deep veins through short veins called connecting veins. Valves in these veins allow blood to flow from the superficial veins to your deep veins, but not the other way.

Use this interactive 3-D diagram to explore the venous system.

Many conditions can affect your venous system. Some of the most common ones include:

Deep vein thrombosis (DVT). A blood clot forms in a deep vein, usually in your leg. This clot can potentially travel to your lungs, causing pulmonary embolism.

Superficial thrombophlebitis. An inflamed superficial vein, usually in your leg, develops a blood clot. While the clot can occasionally travel to a deep vein, causing DVT, thrombophlebitis is generally less serious than DVT.

Varicose veins. Superficial veins near the surface of the skin visibly swell. This happens when one-way valves break down or vein walls weaken, allowing blood to flow backward.

Chronic venous insufficiency. Blood collects in the superficial and deep veins of your legs due to improper functioning of one-way valves. While similar to varicose veins, chronic venous insufficiency usually causes more symptoms, including coarse skin texture and ulcers in some cases.

While the symptoms of a venous condition can vary widely, some common ones include:

inflammation or swelling

tenderness or pain

veins that feel warm to the touch

a burning or itching sensation

These symptoms are especially common in your legs. If you notice any of these and they don't improve after a few days, make an appointment with your doctor.

They can perform a venography. In this procedure, your doctor injects contrast die into your veins to produce an X-ray image of a particular area.

Follow these tips to keep your vein walls and valves strong and properly functioning:

Get regular exercise to keep blood moving through your veins.

Try to maintain a healthy weight, which reduces your risk of high blood pressure. High blood pressure can weaken your veins overtime due to added pressure.

Avoid long periods of standing or sitting. Try to change positions regularly throughout the day.

When sitting down, avoid crossing your legs for long periods of time or regularly switch positions so one leg isn't on top for a long period of time.

When flying, drink plenty of water and try to stand up and stretch as often as possible. Even while sitting, you can flex your ankles to encourage blood flow.

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Venous System: Vein Anatomy and Function, Vein Types, Conditions

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Your venous system is a network of veins that carry blood back to your heart from other organs. We'll explain the basic structure of a vein before diving into different types of veins and their functions. Explore the venous system with an interactive diagram and learn some tips for improving the health of your veins.

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There are five different types of blood vessels. There are arteries, arterioles, capillaries, veins and venules. These blood vessels transport blood throughout the body and supply oxygen to the body.

Link --> Video https://www.youtube.com/watch?v=xToG533PkHI

Genre --> Science

Readability Level --> N/A

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Anatomy and Physiology of Blood Vessels anatomy and physiology for dummies 3d anatomy heart arteries human anatomy & physiology anatomy games anatomy book anatomical models circulation of blood anatomy and physiology test human anatomy model anatomy posters anatomy physiology anatomy and physiology notes anatomy chart anatomy art skeleton anatomy cardiovascular physiology the human anatomy human anatomy muscles holes anatomy and physiology skeleton models anatomy and physiology study guide anatomy and physiology quizzes anatomy and physiology for nurses what is anatomy and physiology anatomy pictures anatomy human picture of human anatomy human anatomy diagrams

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Arteries carry oxygenated blood through the body. The blood moves through the arteries away from the heart. Arteries lead to arterioles that move into capillaries.

Link --> Website https://www.healthline.com/health/arteries-of-the-body

Genre --> Science

Readability Level --> Proficient

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Your circulatory system contains a vast network of blood vessels, which includes arteries, veins, and capillaries.

According to the Cleveland Clinic, if you laid out all of the blood vessels of the body they would be about 60,000 miles long!

Arteries are a type of blood vessel. They work to carry blood away from the heart. In contrast, veins carry blood back to the heart.

Because arteries are moving blood being pumped out by the heart, the walls of arteries are thicker and more elastic than those of veins. This is because the blood in the arteries is passing through with a higher pressure than in veins. The thick, elastic walls of arteries accommodate that pressure.

Read on to discover more about the body's network of arteries.

Arteries carry blood away from the heart in two distinct pathways:

The systemic circuit. In this pathway, oxygen-rich blood is carried away from the heart and toward tissues of the body.

The pulmonary circuit. In the pulmonary circuit, oxygen-depleted blood is carried away from the heart and into the lungs where it can acquire fresh oxygen and get rid of carbon dioxide.

Arteries can also be divided into elastic and muscular arteries based off of the material of their tunica media or middle layer.

Elastic arteries

are closer to the heart where blood pressure is highest

contain more elastic fibers, which allows them to both expand and contract with the surges of blood that occur when the heart beats

Muscular arteries

are further from the heart where blood pressure is lower

contain more smooth muscle tissue and less elastic fibers

Artery wall layers

The walls of arteries are three distinct layers:

Tunica intima. The innermost layer that's made up of cells called endothelial cells as well as elastic fibers.

Tunica media. The middle, and often the thickest layer, that's made up of smooth muscle cells and elastic fibers that can help control the diameter of the blood vessel.

Tunica externa. The outermost layer that's made up of elastic fibers and collagen. This layer predominantly provides structure and support.

Artery sizes

Arteries come in a variety of sizes. The largest artery of the body is the aorta, which begins at the heart.

As they move further from the heart, arteries branch off and become increasingly smaller. The smallest arteries are called arterioles.

Arterioles connect to capillaries, which are the smallest blood vessels and are where the exchange of oxygen, nutrients, and waste occurs between the blood and the cells of the body.

After this exchange occurs, the blood enters the venous system, where it travels back toward the heart.

Below are some of the major arteries that are found in the body and the organs and tissues that they service.

The largest and most important artery in the circulatory system is the aorta. It's so important because it serves as the initial pathway for blood that's leaving the heart and going to the rest of the body via smaller, branching arteries.

Without the aorta, the body's tissues wouldn't get the oxygen and nutrients that they need.

The aorta is connected to your heart via the aortic valve. It's formed of the following parts:

Ascending aorta. The ascending aorta distributes oxygen and nutrients to the heart via the coronary arteries.

Aortic arch. This has three major branches - the brachiocephalic trunk, the left common carotid artery, and the left subclavian artery. It sends blood to the upper body, including the head, neck, and arms.

Descending aorta. The descending aorta sends blood to your torso, abdomen, and lower body. It's referred to as the thoracic aorta above the diaphragm, but after passing the diaphragm, it becomes the abdominal aorta.

There are several head and neck arteries:

Left and right common carotid. The left common carotid comes directly off the aortic arch, while the right common carotid comes from the brachiocephalic trunk.

External carotid. These paired arteries are derived from the common carotid arteries. The external carotid supplies blood to areas like the face, lower jaw, and neck.

Internal carotid. Like the external carotid, these paired arteries are also derived from the common carotid arteries. They're the primary arteries supplying blood to the brain.

Vertebral. Formed off of the subclavian arteries, these paired arteries travel up the neck, where they also supply blood to the brain.

Thyrocervical trunk. Also derived from the subclavian arteries, the thyrocervical trunk branches into several vessels that send blood to the thyroid, neck, and upper back.

The torso arteries include:

Bronchial. There are typically two bronchial arteries, one on the left and one on the right. They supply blood to the lungs.

Esophageal. The esophageal artery provides blood to the esophagus.

Pericardial. This artery supplies blood to the pericardium, which is a membrane that surrounds the heart.

Intercostal. The intercostal arteries are a pair of arteries on either side of the body that send blood to various areas of the torso, including the vertebrae, spinal cord, back muscles, and skin.

Superior phrenic. Like the intercostal arteries, the superior phrenic arteries are paired and deliver blood to the vertebrae, spinal cord, skin, and diaphragm.

The abdominal arteries include:

Celiac trunk. Branching off from the abdominal aorta, the celiac trunk divides into smaller arteries that supply organs such as the stomach, liver, and spleen.

Superior mesenteric. Also branching off of the abdominal aorta, it sends blood to the small intestine, pancreas, and most of the large intestine.

Inferior mesenteric. Like the superior mesenteric artery, this artery also branches off of the abdominal aorta and supplies blood to the last portion of the large intestine, which includes the rectum.

Inferior phrenic. These are paired arteries that supply blood to the diaphragm.

Adrenal. The adrenal arteries are paired arteries that send blood to the adrenal glands.

Renal. These paired arteries deliver blood to the kidneys.

Lumbar. These paired arteries send blood to the vertebrae and spinal cord.

Gonadal. The gonadal arteries are paired arteries that send blood to the testes in males and the ovaries in females.

Common iliac. This branch of the abdominal aorta divides into the internal and external iliac arteries.

Internal iliac. Derived from the common iliac artery, this artery supplies blood to the bladder, pelvis, and external portion of the genitals. It also supplies the uterus and vagina in females.

External iliac. Also arising from the common iliac artery, this artery eventually becomes the femoral artery.

The arteries of the arm are the:

Axillary. This is the name given to the subclavian artery as it exits the torso and enters the arm.

Brachial. This delivers blood to the upper region of the arm.

Radial and ulnar. These run alongside the two bones of the forearm where they eventually divide to deliver blood to the wrist and hand.

Leg arteries include:

Femoral. Derived from the external iliac artery, this artery supplies blood to the thigh and divides into the various smaller arteries that supply the legs.

Genicular. This supplies blood to the knee region.

Popliteal. This is the name given to the femoral artery as it passes below the knee.

Anterior and posterior tibial. Derived from the popliteal artery, these arteries supply blood to the lower portion of the leg. When they reach the ankle, they divide further to supply the ankle and foot region.

The arteries are blood vessels in the circulatory system that move blood away from the heart. This occurs through two different circuits.

The systemic circuit supplies the organs and tissues of the body with oxygen and other nutrients. The pulmonary circuit allows blood to acquire fresh oxygen while getting rid of carbon dioxide.

Because of their vital function, it's important to keep arteries healthy. Damaged or narrowed arteries can lead to the body not getting an adequate blood supply, which can put you at risk for things such as heart attack or stroke.

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Arteries of the Body: Picture, Anatomy, Definition & More

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Your circulatory system contains a vast network of blood vessels, which includes arteries, veins, and capillaries. According to the Cleveland Clinic, if you laid out all of the blood vessels of the body they would be about 60,000 miles long! Arteries are a type of blood vessel.

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Cardiovascular disease is the leading cause of illness and death in the United States. Diseases include a stroke, aneurism and blood clots.

Link --> Case Study https://www.nejm.org/doi/full/10.1056/nejmra035098

Genre --> Science

Readability Level --> Advanced

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Vasodilation, or the widening of blood vessels, happens naturally in your body when an increase in blood flow to tissues in your body is needed.

Link --> Website https://www.healthline.com/health/vasodilation

Genre --> Science

Readability Level --> Basic

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Overview

The short answer is, mostly. Vasodilation, or the widening of blood vessels, happens naturally in your body when an increase in blood flow to tissues in your body is needed. It's a normal process but it can also be part of health issues.

First we'll look at triggers of vasodilation that you might recognize.

There are many possible causes of vasodilation. Some of them include:

Alcohol

One of the immediate effects of alcohol is vasodilation. This is one of the reasons you may feel warm, sweat, or have flushed skin if you've been drinking.

Exercise

As you exercise, your muscle cells consume more and more energy, leading to a decrease in nutrients and an increase in molecules such as carbon dioxide.

This can lead to vasodilation, as the muscles you're exercising require more nutrients and oxygen.

Inflammation

Inflammation can occur due to a variety of injuries, diseases, or conditions. Vasodilation happens during the inflammatory process in order to allow increased blood flow to the affected area.

This is what causes the heat and redness associated with inflammation.

Temperature

You have receptors in your body called thermoreceptors, which detect changes in the temperature of your environment.

When your thermoreceptors pick up on a higher amount of warmth in your environment relative to cold, vasodilation will occur.

This directs a higher flow of blood toward your skin in an effort to dissipate any excess warmth you're feeling.

Vasodilator substances produced by the body

There are many substances that your body produces that can lead to vasodilation.

Some examples include things such as nitric oxide and carbon dioxide as well as hormones such as acetylcholine, prostaglandins, and histamine.

Vasodilator medications

Drugs called vasodilators can cause your blood vessels to widen.

They can either act directly on the smooth muscle of the blood vessels or on your autonomic nervous system, which is the part of your nervous system that regulates vasodilation and vasoconstriction.

Vasodilation is the widening of your blood vessels. It happens when smooth muscles found in the walls of arteries or large veins relax, allowing the blood vessels to become more open.

This leads to an increase in blood flow through your blood vessels as well as a decrease in blood pressure.

There are a variety of conditions that can lead to vasodilation. Below, we'll explore some examples and discuss why vasodilation is an important factor.

Conditions or diseases that cause inflammation

Vasodilation is an important aspect of inflammation. It increases blood flow to the area and also increases the permeability, or leakiness, of the blood vessel walls. Both of these factors help immune cells to more effectively reach the affected area.

Inflammation is a process that's meant to help rid our bodies of foreign invaders, but in some cases it can be harmful, such as in severe allergic reactions and chronic inflammatory diseases.

Vasodilation related to inflammation can be observed in the following scenarios:

Injuries, such as getting a splinter or scrape or twisting an ankle

Infections, such as when your nose becomes red and stuffs up during a cold or when an infected wound becomes red and hot to the touch

Allergic reactions, which occur when your immune system reacts to a harmless foreign substance. Histamine plays a large role in promoting vasodilation in this case.

Chronic diseases or conditions, particularly those in which the immune system attacks healthy cells of the body. Some examples include rheumatoid arthritis, lupus, and inflammatory bowel disease (IBS). People with these conditions may exhibit issues with blood vessel function, including dysfunction of vasodilation. This can lead to cardiovascular problems.

Erythromelalgia

Erythromelalgia is a rare condition that can affect your hands and feet. Symptoms can include severe burning pain, warmth, and redness in the affected area.

In most people with the condition, symptoms aren't constant but instead occur intermittently.

While what causes erythromelalgia is unknown, some evidence suggests that symptoms may be due to abnormalities in vasodilation and vasoconstriction.

The process of vasodilation naturally leads to a drop in blood pressure. This is due to the widening of the blood vessels, which leads to a greater blood flow and therefore less pressure on the walls of the blood vessels.

Blood pressure that's abnormally low is referred to as hypotension. Hypotension may cause no problems for some people, but for others it can lead to symptoms such as dizziness, fainting, and nausea. Extreme levels of hypotension can be life threatening.

A number of conditions can cause hypotension, including severe allergic reactions (anaphylaxis), blood loss, dehydration, and severe infection. Certain medications, particularly those used to treat high blood pressure can also lead to hypotension.

A variety of environmental and personal factors can also have an impact on vasodilation, including:

Temperature

Vasodilation occurs when you're exposed to warmer temperatures. It helps to direct a higher flow of blood toward your skin in order to keep your core body temperature at a normal level.

Prolonged exposure to high temperatures can affect your body's ability to regulate its temperature, leading to conditions such as heat exhaustion and heat stroke.

Elevation

As you move to higher elevations, there's less oxygen available in the air that you breathe.

Your body initially responds to this lack of oxygen through vasodilation, allowing more blood flow to your tissues. However, this is then followed by vasoconstriction.

The accompanying vasoconstriction can lead to an increase in blood pressure as well as buildup of fluid in tissues such as the lungs. This condition is called high-altitude pulmonary edema and can be life-threatening. The condition may be treated with vasodilator drugs or supplemental oxygen.

Age

Increasing age is associated with a decrease in function of blood vessels, including vasodilation. This can contribute to the risk of cardiovascular events such as heart disease and stroke.

Weight

People that are obese have been observed to have dysfunction in vasodilation.

In an obese individual, blood vessels are more resistant to vasodilation, which can lead to cardiovascular issues. Weight loss can help to alleviate the dysfunction in vasodilation.

Vasodilator drugs are medications that can cause vasodilation. Many can act directly on the smooth muscle found in the walls of blood vessels. Others can act on the part of the nervous system that regulates vasodilation and vasoconstriction.

Because vasodilation lowers blood pressure, doctors often prescribe vasodilators for conditions such as high blood pressure or heart failure. Some vasodilators are strong medications and can cause side effects such as fast heartbeat, fluid retention, and flushing.

Viagra is an example of a drug that effects vasodilation and isn't primarily used for high blood pressure treatment. It helps treat erectile dysfunction by affecting the biological pathways that lead to vasodilation of the smooth muscle.

This leads to an increase in blood flow to the penis. A secondary use for Viagra is treating some forms of high blood pressure.

Vasoconstriction is the opposite of vasodilation. While vasodilation is the widening of your blood vessels, vasoconstriction is the narrowing of blood vessels. It's due to a contraction of muscles in the blood vessels.

When vasoconstriction occurs, the blood flow to some of your body's tissues becomes restricted. Your blood pressure also rises.

Vasodilation occurs naturally in your body in response to triggers such as low oxygen levels, a decrease in available nutrients, and increases in temperature.

It causes the widening of your blood vessels, which in turn increases blood flow and lowers blood pressure.

Although vasodilation is a natural process, there are situations in which it can be harmful, such as in severe hypotension, allergic reactions, and strong inflammatory responses.

Additionally, factors such as age and weight can also negatively affect vasodilation.

Nonetheless, inducing vasodilation can be a valuable tool to treat conditions such as high blood pressure and even sickness related to high altitude.

# data[].attributes.attachment_link.title
Vasodilation: Your Blood Vessels Opening

# data[].attributes.attachment_link.description
Vasodilation is a natural process that happens in your body. In some situations it can be harmful, yet in others causing vasodilation is important treatment for a condition. We unpack the good and the bad of this process for you and your blood vessels.

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This video is a fun way to remember how blood flows through the heart. This is from the tv show happy days and gives a memorable bet to help us remember blood flow.

Link --> Video/Music https://www.youtube.com/watch?v=o-4L0xoa-sg

Genre --> Science

Readability Level --> N/A

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Pump Your Blood by Anson Williams (Potsie) - Happy Days

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Circulating concentration of lipoprotein, a large glycoprotein attached to a low-density lipoprotein–like particle, may be associated with risk of coronary heart disease and stroke.

Link --> Case Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272390/

Genre --> Science

Readability Level --> Advanced

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The Emerging Risk Factors Collaboration*

Abstract

Context

Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke.

Objective

To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes.

Study Selection

Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators.

Data Extraction

Individual records were provided for each of 126 634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22 076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline.

Data Synthesis

Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer.

Conclusion

Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

Lipoprotein(a)(Lp[a]) is a low density lipoprotein (LDL)- like particle synthesized by the liver that consists of an apolipoprotein B100 (apo B ₁₀₀) molecule covalently linked to a very large glycoprotein known as apolipoprotein(a) (apo[a]). The physiological and vascular effects of the particle remain uncertain, but Lp(a) has been shown to enter the arterial intima of humans; in vitro and animal studies have reported that Lp(a) can promote thrombosis, inflammation, and foam cell formation.

Many prospective epidemiological studies have reported positive associations of baseline Lp(a) concentration with coronary heart disease (CHD) risk. A literature-based meta-analysis of published data from 31 prospective studies reported a relative risk of 1.5 (95% confidence interval [CI], 1.3-1.6) in a comparison of people in the top third vs those in the bottom third of the Lp(a) distribution (corresponding to mean values in these categories of approximately 50 vs 5 mg/dL). However, such reviews have been insufficiently detailed to enable reliable assessment of the nature of any independent association with CHD and have not addressed possible associations with ischemic stroke and nonvascular outcomes. In particular, Lp(a) concentration is believed to be correlated with some lipid markers, but published studies have not adjusted for them in a consistent way.

It has been suggested that Lp(a) is associated with CHD only at very high concentrations, but this suggestion is controversial, indicating that studies with greater power than hitherto are needed to characterize the shape of any dose-response relationship reliably.

The objective of this report is to produce reliable estimates of associations of Lp(a) with CHD, stroke, and non-vascular mortality, incorporating adjustment for potential confounding by risk factors. The present study differs from previous reports on Lp(a) in several important ways that enhance its scientific value and reliability. First, it is large and comprehensive. Second, harmonization of individual records allows a consistent approach to adjustment for lipids and other potential confounders. Third, correction for within-person variation (regression dilution) in Lp(a) concentration and in potential confounders has been made by use of serial measurements in a subset of participants. Fourth, individual records are available for each participant, allowing detailed analyses under different circumstances (such as by age or at different lipid levels). Fifth, individuals with known preexisting CHD and stroke are excluded, limiting any effects of clinically evident disease on Lp(a) concentration (ie, reverse causality). Given the substantial variations in average Lp(a) levels across available studies, we emphasize that the current analyses compare participants only within each contributing study.

METHODS

Study Design

Details of study selection, data collection, and harmonization procedures in the Emerging Risk Factors Collaboration (ERFC) have been described previously. Studies were identified through electronic searches of databases, scanning of the reference lists of relevant articles (including previously published reviews), and discussion with collaborators of the ERFC (). Electronic searches, not limited to the English language, were performed in MEDLINE and EMBASE for studies published between January 1970 and March 2009 using terms related to Lp(a) (eg, lipoprotein[a], Lp[a], apo[a], apolipoprotein[a]) and cardiovascular disease outcomes (eg, cardiovascular disease, coronary heart disease, myocardial infarction, stroke).

Studies were considered for inclusion if they had baseline information on age, sex, Lp(a), and several conventional vascular risk factors; if they did not select participants on the basis of having previous cardiovascular disease; used quantitative Lp(a) assay methods; recorded cause-specific mortality and/or major vascular morbidity using accepted criteria; and had accrued more than 1 year of follow-up.

Thirty-six eligible prospective studies, including 12 that had not previously published their findings (references 21, 24, 29, 31, 32, 38- 42, 47, 50), were included. These studies involved a total of 126 634 individuals who had no known prior history of CHD (ie, myocardial infarction [MI] or angina, which was defined in each study) or stroke at the initial (baseline) examination. The contributing studies comprise about 90% of relevant incident CHD cases identified in known Western studies (); several smaller studies (collectively comprising about 10% of relevant known incident CHD cases) could not supply data. A few studies could not be included because they did not use quantitative assay methods.

Table 1

Concomitant information was available on Lp(a), age, sex, systolic blood pressure, smoking habits, history of diabetes, body mass index, triglycerides, and total cholesterol in 106 645 participants from 30 studies. A total of 96 113 participants from 26 studies had concomitant data on all the preceding characteristics plus high-density lipoprotein (HDL) cholesterol. To measure Lp(a), 2 studies used in-house assays, 32 used commercially available assays, and 2 did not specify the assay used. Twenty-one studies used enzyme-linked immunosorbent assay methods, 9 immunoturbimetry or nephelometry, 3 immunoradiometry, and 1enzyme immunodiffusion ( eTable 1; available at http://www.jama.com). Twenty-four studies used assays insensitive to apo(a) isoforms.

In registering fatal outcomes, all contributing studies used International Classification of Diseases coding to at least 3 digits and ascertainment was based on death certificates. Twenty-eight of the 36 contributing studies also involved medical records, autopsy findings, and other supplementary sources to help classify deaths ( eTable 2). Twenty-nine studies used standard definitions of MI based on Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) or World Health Organization criteria. Twenty-five studies reported diagnosis of strokes on the basis of typical clinical features and characteristic changes on brain imaging, and most attempted to provide attribution of stroke subtype.

Statistical Analyses

Details of the statistical methods are provided in eAppendixes 1 and 2. Normal distributions were achieved by taking natural logarithms (log) of Lp(a). The pooled standard deviation across studies in baseline log Lp(a) concentration was 1.25, which corresponds to about a 3.5-fold difference (ie, e 1.25) on the original scale of Lp(a) measurement in milligrams per deciliter. The primary disease outcome was CHD (ie, first-ever MI or fatal CHD), with subsidiary analyses of stroke by subtype and all cardiovascular deaths. Analyses involved a 2-stage approach with estimates of association calculated separately within each study before pooling across studies by random-effects meta-analysis. Parallel analyses using fixed-effect models yielded very similar results ( eFigure 1).

For the 26 studies analysed as prospective cohort studies, hazard ratios were calculated using Cox proportional hazard regression models stratified by sex (and, where appropriate, by study group). The assumptions of the proportionality of hazards for log Lp(a) levels were satisfied. Each participant contributed only either the first nonfatal outcome or death recorded at age 20 years or older (ie, deaths preceded by nonfatal CHD or stroke were not included in the analyses).

For the 10 "nested" case-control studies within prospective cohorts, odds ratios were calculated using either conditional or unconditional logistic regression models, as appropriate. Hazard ratios and odds ratios were assumed to approximate the same relative risk and are collectively described as risk ratios (RRs).

To assess the shape of association, study-specific RRs calculated within overall quantiles (eg, tenths) of baseline Lp(a) levels were combined by multivariate random-effects meta-analysis and plotted against mean usual log Lp(a) levels within each quantile. Ninety-five percent CIs were estimated from the floated variances that reflect the amount of information underlying each group (including the reference group). When associations were approximately log-linear, regression coefficients were calculated to estimate the RR associated with a 3.5-fold (ie, 1-SD) higher Lp(a). Risk ratios were adjusted progressively for age, sex, and several other conventional risk factors, with evidence of association indicated by the Wald χ ² statistic. Heterogeneity between studies was assessed by the I ² statistic. ( I ² is a measure of consistency across studies: the percentage of variance in estimated log RRs that is attributable to between study variation as opposed to sampling variation. Values of I ² close to 0 indicate lack of evidence of heterogeneity.) Diversity at the study level (such as differences by study design or laboratory methods) was investigated by grouping studies by recorded characteristics and by meta-regression. Non-HDL cholesterol (calculated by subtraction of HDL cholesterol from total cholesterol) was used as the principal marker of cholesterol content in proatherogenic lipoproteins ( eAppendix 2).

Because most characteristics in epi-demiological studies are measured with some error and are subject to fluctuations within individuals over time, correction for such regression dilution- ideally, both in levels of Lp(a) and in potential confounding factors-can help avoid biases that may exaggerate or obscure associations. Regression dilution ratios for each characteristic were calculated by regressing serial measurements, taken from participants in the ERFC, on the established baseline vascular risk factors listed above plus baseline levels of Lp(a) and duration of follow-up ( eAppendix 1).

Correction for within-person variation in Lp(a) and in potential confounders was achieved by use of conditional expectations of long-term average (ie, "usual") levels of Lp(a) and error-prone confounders predicted from these regression calibration models, and used in assessments of associations with disease risk, as previously described. Regression calibration models allowed variability in Lp(a) to vary by its baseline levels. Analyses were performed using Stata software, release 10 (StataCorp, College Station, Texas), involving 2-sided statistical tests, a significance level of P<.05, and 95% CIs.

This study was approved by the Cambridgeshire Ethics Review Committee and was conducted and analyzed independently from its funders.

RESULTS

Mean age at entry of participants was 57 (SD, 8) years and 48% were women; 47% were European and 50% North American. During 1.3 million person-years at risk (mean, 10.2 years to first outcome), there were 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause ().

As expected, mean Lp(a) concentration varied across studies, but values were as diverse within groups of studies that used similar assay methods as across studies that used different methods ( eFigure 2). The overall median of Lp(a) at baseline was 12.6 (interquartile range, 4.9-32.1) mg/dL. (To convert to μmol/L, multiply by 0.0357.) Blacks had more than a 100% higher Lp(a) concentration than whites (). Racial groups were examined separately in subanalyses.

Table 2

Correlates and Within-Person Variation Over Time

Lp(a) concentration was weakly correlated with several known or suspected risk factors: positively with total and non-HDL cholesterol, apo B ₁₀₀, and fibrinogen and inversely with log triglycerides. Lp(a) levels were 12% (95% CI, 8%-16%) higher in women and 11% (95% CI, 4%-17%) lower in people with diabetes (). Repeat information on Lp(a) was available in 6597 participants from 7 studies (mean interval, 8.3 years) ( eFigure 3). The regression dilution ratio of loge Lp(a), adjusted for age and sex, was 0.87 (95% CI, 0.81-0.93), which was considerably higher in these studies than those for total cholesterol (0.65; 95% CI, 0.62-0.65), HDL cholesterol (0.72; 95% CI, 0.70-0.75), log tri-glycerides (0.63; 95% CI, 0.61-0.65), or systolic blood pressure (0.52; 95% CI, 0.49-0.55).

Associations With CHD

In analyses adjusted for age and sex only, there were continuous associations of Lp(a) with the risk of CHD, potentially consistent with either a curvilinear or a log-linear shape (). Statistical tests of the compatibility of the data with a linear vs a quadratic model suggested a better fit with a curvilinear shape ( P=.003) ( eAppendix 1 and eTable 3). In analyses restricted to participants with complete information on relevant covariates, the RR for CHD per 3.5-fold higher Lp(a) level, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for systolic blood pressure, smoking, history of diabetes, and total cholesterol (). There was moderate heterogeneity among studies contributing to the fully adjusted CHD result ( I ²=49%; 95% CI, 22%-66%) ().

Table 3

Findings were broadly similar in sub-analyses of coronary death and nonfatal MI ( and eFigure 4), adjusted for non-HDL and HDL cholesterol (instead of total cholesterol) and adjusted for fibrinogen, C-reactive protein, or apo AI and apo B ₁₀₀ ( eTable 4). Because adjustment for total cholesterol may obscure associations of Lp(a) with disease risk because total cholesterol includes the cholesterol contained in Lp(a) particles, we conducted sensitivity analyses that corrected also for estimated Lp(a) cholesterol concentration, which gave a higher RR than without such correction ( eTable 4).

The findings were qualitatively similar in analyses that excluded the first 5 years of follow-up ( eFigure5), ignored regression dilution ( eTable 5), and used fixed-effect models ( eFigure 1). The RR, adjusted for several conventional risk factors, was 1.27 (95% CI, 1.17-1.38) in a comparison of those in the top third with those in the bottom third of baseline Lp(a) concentration ( eTable5). In the cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95%CI, 5.4-5.9) per 1000 person-years and 4.4 (95%CI, 4.2-4.6) per 1000 person-years.

The RRs for CHD did not vary importantly by sex, non-HDL or HDL cholesterol, triglycerides, blood pressure, diabetes, or body mass index (). There was no convincing evidence of major variations in RRs of studies using isoform-sensitive vs isoform-insensitive assays or with other features of study design recorded ( eFigure 6). Subsidiary analyses restricted to people of European continental ancestry (>90% of the participants) yielded very similar findings to the overall findings described herein (data available from the authors on request), but comparisons of RRs between racial groups lacked power because data were limited on other races/ethnicities ( eFigure 6). In a common set of participants, the adjusted RR for CHD per1-SD higher Lp(a) concentration was considerably weaker than the corresponding RR with non-HDL cholesterol (1.14 vs 1.66, respectively) ( eFigure 7).

Associations With Stroke

In analyses adjusted for age and sex only, the shape of association of Lp(a) with the risk of ischemic stroke was indistinct (). Assuming a log-linear association with risk, the age-and-sex-only- adjusted RR for ischemic stroke was 1.11 (95% CI, 1.02-1.20) per 3.5-fold higher usual Lp(a) levels in analyses restricted to participants with complete information on relevant covariates (). The RR was 1.10 (95% CI, 1.02-1.18) following further adjustment for systolic blood pressure, smoking, history of diabetes, and total cholesterol (). There was no clear evidence of heterogeneity among studies contributing to ischemic stroke ( I ²=30%;,95%CI,0%-64%).The adjusted RRs per 3.5-fold higher usual Lp(a) levels were 1.01 (95%CI, 0.92-1.12) for unclassified stroke and 1.06 (95% CI, 0.901.26) for hemorrhagic stroke ().

Associations With Nonvascular Mortality

The adjusted RR for the aggregate of nonvascular mortality was 1.01 (95% CI, 0.98-1.05) (). The adjusted RRs were 1.00 (95% CI, 0.97-1.04) for all cancer deaths and 1.03 (95% CI, 0.97-1.09) for smoking-related cancer deaths. The adjusted RR for nonvascular deaths other than cancer was 1.00 (95% CI, 0.95-1.06). There were too few cases of particular types of cancer (or other nonvascular outcomes) to enable reliable analyses by subtype. Adjusted RRs for major vascular and nonvascular outcomes were qualitatively similar in analyses that included fatal outcomes without censoring previous nonfatal outcomes ( eFigure 8).

COMMENT

Contrary to previous suggestions of steep threshold effects, the current analysis of 126 634 individuals has demonstrated broadly continuous associations of Lp(a) concentration with the risk of CHD. Because these associations were only slightly reduced after adjustment for long-term average levels of lipids and other established risk factors, it increases the likelihood that Lp(a) is an independent risk factor for CHD. Lipoprotein(a) concentration is, however, a relatively modest coronary risk factor, being only about one-quarter as strong overall as non-HDL cholesterol, although Lp(a) may become proportionally more important to CHD at very high concentrations owing to its potentially curvilinear risk relationship. Because associations of higher Lp(a) concentration with CHD are similar at different levels of non-HDL cholesterol, the absolute benefits of cholesterol lowering should be greater if Lp(a) concentration is high (or when absolute risk is high for some other reason).

Whereas previous literature-based reviews of Lp(a) have focused only on CHD, the current individual participant meta-analysis also investigated stroke subtypes and cause-specific mortality, including nonvascular deaths. Although current data in relation to Lp(a) concentration and stroke were somewhat sparser and less distinct than those for CHD, findings were broadly similar to those for CHD. In contrast, Lp(a) concentration was unrelated to the aggregate of nonvascular mortality, including cancer and noncancer deaths. Hence, Lp(a) appears to be more specifically associated with vascular outcomes than are a number of systemic markers of inflammation that have been strongly associated with both vascular and nonvascular outcomes. As a subsidiary finding, the current analyses convincingly demonstrate that Lp(a) concentration is more consistent within individuals over several years than are levels of total cholesterol, HDL cholesterol, or systolic blood pressure.

Recent large studies have reported highly significant associations of variants in or near the LPA gene (a locus known to strongly influence circulating Lp[a] concentration)76-78 with CHD risk. Together with the current findings of continuous, independent, and specific associations of Lp(a) concentration with vascular outcomes, available data are consistent with the existence of a causal relationship and increase priority for investigation of Lp(a) as a potential therapeutic target. Because the current findings show that Lp(a) concentration is a relatively modest risk factor for CHD, however, interventions capable of much more powerful and specific Lp(a) lowering than currently available may be required to demonstrate any vascular benefits in randomized trials.

Substantial modification of Lp(a) concentration has been difficult to achieve without pharmacological agents. Niacin and certain inhibitors of cholesteryl ester transfer protein can reduce Lp(a) by about 20% and about 40%, respectively. Contradictory findings have been reported about the effect of statins on Lp(a) concentration, and it remains uncertain whether statin use attenuates the CHD risk associated with Lp(a) concentration. Large randomized trials of niacin and cholesteryl ester transfer protein inhibitors in the secondary prevention of CHD are in progress. Such studies may not, however, enable causal inferences because, in addition to Lp(a) lowering, these agents increase HDL cholesterol and decrease LDL cholesterol and triglyceride concentrations. Similar considerations may apply to mipomersen, an antisense oligonucleotide directed at human apo B ₁₀₀ now in phase 2 clinical trials that has been shown to reduce circulating Lp(a) concentration by 70% in transgenic mice, as well as reducing LDL cholesterol, apo B ₁₀₀, and oxidized phospholipids.

Even though the first epidemiological study of Lp(a) and CHD was reported in 1972, the investigation of this lipoprotein as a potential cardiovascular risk factor has been hampered by the lack of consistent approaches to its measurement. International reference material for Lp(a) laboratory standardization emerged only in 2000 and was accepted by the World Health Organization in 2003. Even with methods that use the same standard, however, there is significant variability in measured Lp(a) concentration if assays are sensitive to variation in numbers of repeat domains in apo(a). Hence, in 2003 an expert panel recommended use of assay systems not sensitive to apo(a) isoforms ( eFigure 2B). Population differences can also contribute to variation in Lp(a) concentration, particularly since values differ substantially between individuals and are highly heritable. Nevertheless, pooled analyses of individual data from prospective studies should remain informative, provided that, as in the current study, analyses compare cases and noncases only within each study and explore potential diversity across groups of studies using similar assay methods.

Despite considerable scope for such diversity, it is notable that there is relatively moderate heterogeneity in RRs among the studies based in 15 different Western countries contributing to the current findings, an observation that supports the ability to generalize these data to such populations. Because more than 90% of the participants in the current study were of European continental ancestry, however, further studies are needed in non-white racial groups, particularly in black and South Asian populations, which have different Lp(a) concentrations. The RRs in the current analysis were not strongly different between studies using assays sensitive and insensitive to apo(a) isoforms (although there was, of course, some heterogeneity within each of these groups of studies). Although the findings did not differ appreciably in subgroups defined by the laboratory and population features recorded, further studies are needed that can explore in greater depth such potential sources of heterogeneity and joint effects with other lipid markers. For example, large studies are needed to assess whether Lp(a) particles with smaller-sized apo(a) isoforms confer even higher RRs for CHD (such assessment was not possible in the current study because it lacked concomitant data on apo[a] isoforms). Similarly, larger studies are needed to assess proposed synergy in the promotion of vascular disease through oxidative damage (again, this was not possible in the current study because the data set lacked concomitant information on oxidized LDL and lipoprotein-associated phospholipase A ₂).

CONCLUSION

Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with the risk of CHD and stroke that appear exclusive to vascular outcomes.

Acknowledgments

Funding/Support: The ERFC Coordinating Centre is supported by a program grant from the British Heart Foundation (RG/08/014) and supported by grants from the UK Medical Research Council and the BUPA Foundation. Aspects of this work have been supported by unrestricted educational grants from GlaxoSmithKline and a grant from Merck Sharp and Dohme in relation to Lp(a). A variety of sources have supported recruitment, follow-up, and laboratory measurements in the 116 cohorts contributing to the ERFC. Investigators of several of these studies have contributed to a list naming some of these funding sources, available at http://www.phpc.cam.ac.uk/MEU/. Dr Erqou is supported by a Gates Cambridge Trust and Overseas Studentship Award. Drs Di Angelantonio and Thompson have been supported by UK Medical Research Council PhD studentships.

Role of the Sponsor: None of the sponsors had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Footnotes

Authors/Writing Committee: The following members of the Emerging Risk Factors Collaboration take authorship responsibility for the study results: Sebhat Erqou, MD, Stephen Kaptoge, PhD, Philip L. Perry, MBChB, Emanuele Di Angelantonio, MD, University of Cambridge, Cambridge, England; Alexander Thompson, PhD, University of Cambridge; Ian R. White, MSc, MRC Biostatistics Unit, Cambridge, England; Santica M. Marcovina, PhD, University of Washington, Seattle; Rory Collins, FMedSci, University of Oxford, Oxford, England; Simon G. Thompson, DSc, MRC Biostatistics Unit; John Danesh, FRCP, University of Cambridge.

Author Contributions: Drs Erqou and Danesh had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the analyses.

Study concept and design: Erqou, Kaptoge, Di Angelantonio, Thompson, White, Marcovina, Thompson, Danesh.

Acquisition of data: Erqou, Kaptoge, Perry, Di Angelantonio, Thompson, White, Collins, Thompson, Danesh.

Analysis and interpretation of data: Erqou, Kaptoge, Perry, Di Angelantonio, Thompson, White, Marcovina, Collins, Thompson, Danesh.

Drafting of the manuscript: Erqou, Di Angelantonio, Danesh.

Critical revision of the manuscript for important in-tellectual content: Erqou, Kaptoge, Perry, Di Angelantonio, Thompson, White, Marcovina, Collins, Thompson, Danesh.

Statistical analysis: Erqou, Kaptoge, Perry, Di Angelantonio, Thompson.

Obtained funding: Danesh.

Administrative, technical, or material support: Kaptoge, Thompson, White, Marcovina, Collins, Thompson, Danesh.

Study supervision: Thompson, Danesh.

Financial Disclosures: Dr Collins reports having received research funding from AstraZeneca, Bayer, British Heart Foundation, Cancer Research UK, European Union, Kadoorie Trust, Medical Research Council, Merck, Schering, Solvay, and UK Biobank. Dr Danesh reports having received research funding from the British Heart Foundation, BUPA Foundation, diaDexus, European Union, Evelyn Trust, GlaxoSmithKline, Medical Research Council, Merck Sharp and Dohme, Roche, and Wellcome Trust. No other disclosures were reported.

Investigators/Contributors: (Appendix 1 in Danesh et al lists the study acronyms.) AFTCAPS: Robert W. Tipping, MS, Merck Research Laboratories, United States; ALLHAT: Charles E. Ford, PhD, University of Texas School of Public Health, United States; Lara M. Simpson, PhD, University of Texas School of Public Health, United States; AMORIS: Göran Walldius, MD, Karolinska Institutet, Sweden; Ingmar Jungner, MD, Karolinska Institutet, Sweden; ARIC: Aaron R. Folsom, MD, University of Minnesota, United States; Lloyd Chambless, PhD, University of North Carolina, United States; ATTICA: Demosthenes Panagiotakos, MD, Harokopio University, Greece; Christos Pit-savos, MD, University of Athens, Greece; Christina Chrysohoou, MD, University of Athens, Greece; Christodoulos Stefanadis, MD, University of Athens, Greece; BIP: Uri Goldbourt, PhD, Sheba Medical Center, Israel; Michal Benderly, PhD, Sheba Medical Center, Israel; David Tanne, MD, Sheba Medical Center, Israel; BRHS: Peter Whin-cup, FRCP, University of London, England; S. Goya Wannamethee, PhD, University College London, England; Richard W. Morris, PhD, University College London, England; BRUN: Stefan Kiechl, MD, Medical University Innsbruck, Austria; Johann Willeit, MD, Medical University Innsbruck, Austria; Peter Santer, MD, Bruneck Hospital, Italy; Agnes Mayr, MD, Bruneck Hospital, Italy; BUPA: Nicholas Wald, FRS, Wolfson Institute of Preventive Medicine, England; BWHHS: Shah Ebrahim, DM, London School of Hygiene & Tropical Medicine, England; Debbie Lawlor, PhD, University of Bristol, England; CaPS: John Yarnell, MD, Queen's University of Belfast, Northern Ireland; John Gallacher, PhD, Cardiff University, Wales; CASTEL: Edoardo Casiglia, MD, University of Padova, Italy; Valerie Tikhonoff, MD, University of Padova, Italy; CHARL: Paul J. Nietert, PhD, Medical University of South Carolina, United States; Susan E. Sutherland, PhD, Medical University of South Carolina, United States; David L. Bachman, MD, Medical University of South Carolina, United States; CHS: Mary Cushman, MD, University of Vermont, United States; Bruce M. Psaty, MD, University of Washington, United States; Russ Tracy, PhD, University of Vermont, United States (see http://chs-nhlbi.org for acknowledgments); COPEN: Anne Tybjærg-Hansen, MD, University of Copenhagen, Denmark; Børge G. Nordestgaard, MD, University of Copenhagen, Denmark; Ruth Frikke-Schmidt, MD, University of Copenhagen, Den-mark; Pia R. Kamstrup, MD, University of Copenhagen, Denmark; CUORE: Simona Giampaoli, MD, Istituto Superiore di Sanità, Italy; Luigi Palmieri, DrStat, Istituto Superiore di Sanità, Italy; Salvatore Panico, MD, Federico II University, Italy; Diego Vanuzzo, MD, Centre for Cardiovascular Prevention, Italy; Lorenza Pilotto, MD, Centre for Cardiovascular Prevention, Italy; DRECE: Agustın Gomez de la Camara, MD, Hospital 12 de Octubre, Spain; Juan A. Gomez Gerique, PhD, Hospital Marques de Valdecilla, Spain; DUBBO: Leon Simons, MD, University of New South Wales, Australia; John McCallum, DPhil, Victoria University, Australia; Yechiel Friedlander, PhD, Hebrew University, Israel; EAS: F. Gerry R. Fowkes, MBChB, University of Edinburgh, Scotland; Amanda Lee, PhD, University of Edinburgh, Scotland; Felicity B. Smith, PhD, University of Edinburgh, Scotland; EPESEBOS: James Taylor, MD, East Boston Neighborhood Health Center, United States; Jack M. Guralnik, MD, US National Institute on Aging, United States; Caroline L. Phillips, MS, US National Institute on Aging, United States; EPESEIOW: Robert B. Wallace, MD, University of Iowa, United States; Jack M. Guralnik, MD, US National Institute on Aging, United States; Caroline L. Phillips, MS, US National Institute on Aging, United States; EPESENCA: Dan G. Blazer, MD, Duke University Medical Centre, United States; Jack M. Guralnik, MD, US National Institute on Aging, United States; Caroline L. Phillips, MS, US National Institute on Aging, United States; EPESENHA: Caroline L. Phillips, MS, US National Institute on Aging, United States; Jack M. Guralnik, MD, US National Institute on Aging, United States; ESTHER: Hermann Brenner, MD, German Cancer Research Center, Germany; Elke Raum, MD, German Cancer Research Center, Germany; Heiko Müller, DrScHum, German Cancer Research Center, Germany; Dietrich Rothenbacher, MD, German Cancer Research Center, Germany; FIA: Jan-Hakan Jansson, MD, Umea University, Sweden; Patrik Wennberg, MD, Umea University, Sweden; FINE_FIN: Aulikki Nissinen, MD, National Institute for Health and Welfare, Finland; FINE_IT: Chiara Donfrancesco, DrStat, Istituto Superiore di Sanità, Italy; Simona Giampaoli, MD, Istituto Superiore di Sanità, Italy; FINRISK92, FINRISK97: Veikko Salomaa, MD, National Institute for Health and Welfare, Finland; Kennet Harald, MA, National Institute for Health and Welfare, Finland; Pekka Jousilahti, MD, National Institute for Health and Welfare, Finland; Erkki Vartiainen, MD, National Institute for Health and Welfare, Finland; FLETCHER: Mark Woodward, PhD, Mount Sinai School of Medicine, United States; FRAMOFF: Ralph B. D'Agostino, PhD, Boston University, United States; Philip A. Wolf, MD, Boston University School of Medicine, United States; Ramachandran S. Vasan, MD, Boston University School of Medicine, United States; Michael J. Pencina, PhD, Boston University, United States; GLOSTRUP: Else-Marie Bladbjerg, PhD, University of Southern Denmark, Denmark; Torben Jørgensen, MD, University of Copenhagen, Denmark; Lars Møller, MD, World Health Organization; Jørgen Jespersen DSc, University of Southern Denmark, Denmark; GOH: Rachel Dankner, MD, Gertner Institute for Epidemiology and Health Policy Research, Israel; Angela Chetrit, MSc, Gertner Institute for Epidemiology and Health Policy Research, Israel; Flora Lubin, RD, Gertner Institute for Epidemiology and Health Policy Research, Israel; GOTO33, GOTO43: Annika Rosengren, MD, Göteborg University, Sweden; Lars Wilhelmsen, MD, Göteborg University, Sweden; Georgios Lappas, Göteborg University, Sweden; Henry Eriksson, MD, Göteborg University, Sweden; GOTOW: Cecilia Björkelund, MD, Göteborg University, Sweden; Lauren Lissner, PhD, Göteborg University, Sweden; Calle Bengtsson, MD, Göteborg University, Sweden; GRIPS: Peter Cremer, MD, Klinikum der Universität München LMU, Germany; Dorothea Nagel, PhD, Uni-versity of Munich, Germany; HELSINAG: Reijo S. Tilvis, MD, Helsinki University Hospital, Finland; Timo E. Strandberg, MD, Oulu University Hospital, Finland; HONOL: Beatriz Rodriguez, MD, University of Hawaii, United States; HOORN: Jacqueline Dekker, PhD, VU University Medical Center, the Netherlands; G. Nijpels, MD, Vrije Universiteit Medical Center, the Netherlands; Coen D.A. Stehouwer, MD, Maastricht University Medical Centre, the Netherlands; HPFS: Eric Rimm, ScD, Harvard University, United States; Jennifer K. Pai, ScD, Brigham and Women's Hospital, United States; IKNS: Shinichi Sato, MD, Osaka Medical Center for Health Science and Promotion, Japan; Hiroyasu Iso, MD, Osaka University, Japan; Akihiko Kitamura, MD, Osaka Medical Center for Health Science and Promotion, Japan; Hiroyuki Noda, MD, Osaka University, Japan; ISRAEL: Uri Goldbourt, PhD, Sheba Medical Center, Israel; KIHD: Jukka T. Salonen, MD, University of Kuopio, Finland; Kristiina Nyyssönen, PhD, University of Kuopio, Finland; Tomi-Pekka Tuomainen, MD, University of Kuopio, Finland; LASA: Dorly J. H. Deeg, PhD, VU University Medical Centre, the Netherlands; Jan L. Poppelaars, MA, VU University Medical Centre, the Netherlands; MALMO: Bo Hedblad, MD, Lund University, Sweden; Göran Berglund, MD, Lund University, Sweden; Gunnar Engström, MD, Lund University, Sweden; MCVDRFP: W. M. M. Verschuren, PhD, National Institute of Public Health and the Environment, the Netherlands; Anneke Blokstra, MSc, National Institute for Public Health and the Environment, the Netherlands; MOGERAUG1, MOGERAUG2, MOGERAUG3: Angela Döring, MD, German Research Center for Environmental Health, Germany; Wolfgang Koenig, MD, University of Ulm Medical Center, Germany; Christa Meisinger, MD, German Research Center for Environmental Health, Germany; Wilfried Mraz, PhD, University of Munich, Germany; MORGEN: W. M. M. Verschuren, PhD, National Institute of Public Health and the Environment, the Netherlands; Anneke Blokstra, MSc, National Institute for Public Health and the Environment, the Netherlands; H. Bas Bueno-de-Mesquita, PhD, National Institute for Public Health and the Environment, the Netherlands; MOSWEGOT: Lars Wilhelmsen, MD, Göteborg University, Sweden; Annika Rosengren, MD, Göteborg University, Sweden; Georgios Lappas, Göteborg University, Sweden; MRFIT: Lewis H. Kuller, MD, University of Pittsburgh, United States; Greg Grandits, MS, University of Minnesota, United States; NCS: Randi Selmer, PhD, Norwegian Institute of Public Health, Norway; Aage Tverdal, PhD, Norwegian Institute of Public Health, Norway; Wenche Nystad, PhD, Norwegian Institute of Public Health, Norway; NHANES I, NHANES II, NHANES III: R. F. Gillum, MD, Centers for Disease Control and Prevention, United States; Michael Mussolino, PhD, National Institutes of Health, United States; NHS: Eric Rimm, ScD, Harvard University, United States; Sue Hankinson, ScD, Harvard School of Public Health, United States; JoAnn E Manson, MD, Harvard Medical School, United States; Jennifer K. Pai, ScD, Brigham and Women's Hospital, United States; NORTH KARELIA: Veikko Salomaa, MD, National Institute for Health and Welfare, Finland; Kennet Harald, MA, National Institute for Health and Welfare, Finland; Pekka Jousilahti, MD, National Institute for Health and Welfare, Finland; Erkki Vartiainen, MD, National Institute for Health and Welfare, Finland; NPHS II: Jackie A. Cooper, MSc, University College London, England; Kenneth A Bauer, MD, Harvard Medical School, United States; OSAKA: Shinichi Sato, MD, Osaka Medical Center for Health Science and Promotion, Japan; Akihiko Kitamura, MD, Osaka Medical Center for Health Science and Promotion, Japan; Yoshihiko Naito, MD, Mukogawa Women's University, Japan; Hiroyasu Iso, MD, Osaka University, Japan; OSLO: Ingar Holme, PhD, Oslo University Hospital, Norway; Randi Selmer, PhD, Norwegian Institute of Public Health, Norway; Aage Tverdal, PhD, Norwegian Institute of Public Health, Norway; Wenche Nystad, PhD, Norwegian Institute of Public Health, Norway; OYABE: Hideaki Nakagawa, MD, Kanazawa Medical University, Japan; Katsuyuki Miura, MD, Shiga University of Medical Science, Japan; PARIS1: Pierre Ducimetiere, PhD, INSERM, France; Xavier Jouven, MD, INSERM, France; Gerald Luc, MD, University of Lille, France; PRHHP: Carlos J. Crespo, DrPH, Portland State University, United States; Mario R. Garcia Palmieri, MD, University of Puerto Rico, United States; PRIME: Philippe Amouyel, MD, Institut Pasteur de Lille, France; Dominique Arveiler, MD, Universite de Strasbourg, France; Alun Evans, MD, The Queens University of Belfast, Northern Ireland; Jean Ferrieres, MD, University of Toulouse, France; PROCAM: Helmut Schulte, PhD, Assmann-Stiftung für Prävention, Germany; Gerd Assmann FRCP, Assmann-Stiftung für Prävention, Germany; PROSPER: James Shepherd, MD, Glasgow Royal Infirmary, Scotland; Chris J. Packard, DSc, University of Glasgow, Scotland; Naveed Sattar, FRC Path, University of Glasgow, Scotland; Ian Ford, PhD, University of Glasgow, Scotland; QUEBEC: Bernard Cantin, MD, Institutde Cardiologie de Quebec, Ho pital Laval, Canada; Benoıt Lamarche, PhD, Laval University, Canada; Jean-Pierre Despres, PhD, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Canada; Gilles R. Dagenais. MD, Institut Universitaire de Cardiologie et Pneumologie de Quebec, Canada; RANCHO: Elizabeth Barrett-Connor, MD, University of California, United States; Lori B. Daniels, MD, University of California, United States; Gail A. Laughlin, PhD, University of California, United States; REYK: Vilmundur Gudnason, MD, University of Iceland, Iceland; Thor Aspelund, PhD, University of Iceland, Iceland; Gunnar Sigurdsson, MD, University of Iceland, Iceland; Bolli Thorsson, MD, Icelandic Heart Association, Iceland; RIFLE: Maurizio Trevisan, MD, Nevada System of Higher Education, United States; ROTT: Jacqueline Witteman, PhD, Erasmus MC, the Netherlands; Isabella Kardys, MD, Erasmus MC, the Netherlands; Monique M. B. Breteler, MD, Erasmus MC, the Netherlands; Albert Hofman, MD, Erasmus MC, the Netherlands; SHHEC: Hugh Tunstall-Pedoe, MD, University of Dundee, Scotland; Roger Tavendale, PhD, University of Dundee, Scotland; Gordon Lowe, DSc, University of Glasgow, Scotland; Mark Woodward, PhD, Mount Sinai School of Medicine, United States; SPEED: Yoav Ben-Shlomo, PhD, University of Bristol, England; George Davey-Smith, MD, University of Bristol, England; SHS: Barbara V. Howard, PhD, Medstar Research Institute, United States; Ying Zhang, MD, University of Oklahoma Health Sciences Center, United States; Lyle Best, MD, Missouri Breaks Industries Research Inc, United States; Jason Umans, MD, Georgetown University Medical Center, United States; TARFS: Altan Onat, MD, Istanbul University, Turkey; TROMSØ: Inger Njølstad, MD, University of Tromsø, Norway; Ellisiv B. Mathiesen, MD, University of Tromsø, Norway; Maja-Lisa Løchen, PhD, University of Tromsø, Norway; Tom Wilsgaard, PhD, University of Tromsø, Norway; ULSAM: Erik Ingelsson, MD, Karolinska Institutet, Sweden; Johan Sundström, MD, Uppsala University, Sweden; Lars Lind, MD, Uppsala University Hospital, Sweden; Lars Lannfelt, MD, Uppsala University, Sweden; USPHS: J. Michael Gaziano, MD, Brigham and Women's Hospital, United States; Meir Stampfer, MD, Harvard School of Public Health, United States; Paul M Ridker, MD, Brigham and Women's Hospital, United States; USPHS2: J. Michael Gaziano, MD, Brigham and Women's Hospital, United States; Paul M Ridker, MD, Brigham and Women's Hospital, United States; VHMPP: Hanno Ulmer, PhD, Innsbruck Medical University, Austria; Günter Diem, MD, Agency for Preventive and Social Medicine, Austria; Hans Concin, MD, Agency for Preventive and Social Medicine, Austria; VITA: Alberto Tosetto, MD, San Bortolo Hospital, Italy; Francesco Rodeghiero, MD, San Bartolo Hospital, Italy; WHITEI: Michael Marmot, FMedSci, University College London, England; Robert Clarke, MD, University of Oxford, England; Rory Collins, FMedSci, University of Oxford, England; Astrid Fletcher, PhD, London School of Hygiene and Tropical Medicine, England; WHITE II: Eric Brunner, PhD, University College London, England; Martin Shipley, MSc, University College London, England; WHS: Paul M Ridker, MD, Brigham and Women's Hospital, United States; Julie Buring, ScD, Brigham and Women's Hospital, United States; WOSCOPS: James Shepherd, MD, Glasgow Royal Infirmary, Scotland; Stuart Cobbe, FMedSci, BHF Glasgow Cardiovascular Research Centre, Scotland; Ian Ford, PhD, University of Glasgow, Scotland; Michele Robertson, BSc, University of Glasgow, Scotland; XIAN: Yao He, MD, Chinese PLA General Hospital, China; ZARAGOZA: Alejandro Marin Ibanez, MD, San Jose Norte Health Centre, Spain; ZUTE: Edith Feskens, PhD, Wageningen University, the Netherlands; Daan Kromhout, PhD, Wageningen University, the Netherlands.

Investigators/Data Management Team: Matthew Walker, PhD, University of Cambridge, England; Sarah Watson, MMath, University of Cambridge, England.

Investigators/Coordinating Center: Rory Collins, FMedSci, University of Oxford, England; Emanuele Di Angelantonio, MD, University of Cambridge, England; Sebhat Erqou, MD, University of Cambridge, England; Stephen Kaptoge, PhD, University of Cambridge, England; Sarah Lewington, DPhil, University of Oxford, England; Lia Orfei, MSc, University of Cambridge, England; Lisa Pennells, MSc, University of Cambridge, England; Philip L. Perry, MBChB, University of Cambridge, England; Kausik K. Ray, MD, University of Cambridge, England; Nadeem Sarwar, PhD, University of Cambridge, England; Myriam Alexander, MPhil, University of Cambridge, England; Alexander Thompson, PhD, University of Cambridge, England; Simon G. Thompson, DSc, MRC Biostatistics Unit, England; Matthew Walker, PhD, University of Cambridge, England; Sarah Watson, MMath, University of Cambridge, England; Frances Wensley, MSc, University of Cambridge, England; Ian R. White, MSc, MRC Biostatistics Unit, England; Angela M. Wood, PhD, University of Cambridge, England; John Danesh, FRCP, University of Cambridge, England (principal investigator).

Additional Information: eAppendixes 1 through 3, eTables 1 through 5, and eFigures 1 through 8 are available online at http://www.jama.com.

Additional Contributions: Hannah Sneath and Angela Harper, University of Cambridge, provided secretarial support.

REFERENCES

87. Treatment of HDL to reduce the incidence of vas-cular events HPS2-THRIVE. http://clinicaltrials.gov/ct2/show/ NCT00461630. Accessed July 1, 2009.

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Lipoprotein(a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality

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The Emerging Risk Factors Collaboration* Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes.

# data[].attributes.body
Blood flows through the heart from the Vena Cava to the right atrium to the right ventricle to the pulmonary arteries to the pulmonary veins to the left atrium to the left ventricle to the aorta. Then the aorta sends blood throughout the whole body.

Source --> Website https://my.clevelandclinic.org/health/articles/17060-how-does-the-blood-flow-through-your-heart

Genre --> Science

Readability Level --> Basic

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The right and left sides of the heart work together
Right Side
Blood enters the heart through two large veins, the inferior and superior vena cava, emptying oxygen-poor blood from the body into the right atrium.
Left Side
The pulmonary vein empties oxygen-rich blood, from the lungs into the left atrium.

Atrial contraction
Right Side
Blood flows from your right atrium into your right ventricle through the open tricuspid valve. When the ventricles are full, the tricuspid valve shuts. This prevents blood from flowing backward into the atria while the ventricles contract (squeeze).
Left Side
Blood flows from your left atrium into your left ventricle through the open mitral valve. When the ventricles are full, the mitral valve shuts. This prevents blood from flowing backward into the atria while the ventricles contract (squeeze).

Ventricular contraction

Oxygen and carbon dioxide travels to and from tiny air sacs in the lungs, through the walls of the capillaries, into the blood.
Right Side
Blood leaves the heart through the pulmonic valve, into the pulmonary artery and to the lungs.
Left Side
Blood leaves the heart through the aortic valve, into the aorta and to the body. This pattern is repeated, causing blood to flow continuously to the heart, lungs and body.

How does blood flow through your lungs?

Once blood travels through the pulmonic valve, it enters your lungs. This is called the pulmonary circulation. From your pulmonic valve, blood travels to the pulmonary artery to tiny capillary vessels in the lungs. Here, oxygen travels from the tiny air sacs in the lungs, through the walls of the capillaries, into the blood. At the same time, carbon dioxide, a waste product of metabolism, passes from the blood into the air sacs. Carbon dioxide leaves the body when you exhale. Once the blood is purified and oxygenated, it travels back to the left atrium through the pulmonary veins.

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Heart & Blood Vessels: Heart Blood Flow & How It Works

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Right Side Blood enters the heart through two large veins, the inferior and superior vena cava, emptying oxygen-poor blood from the body into the right atrium. Left Side The pulmonary vein empties oxygen-rich blood, from the lungs into the left atrium. Right Side Blood flows from your right atrium into your right ventricle through the open tricuspid valve.

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The circulatory system and the cardiovascular system are connected and they cannot function without the other. The circulatory system has all of the blood vessels.

Link --> Picture

Genre --> Science

Readability Level --> N/A

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Red blood cells receive oxygen from the lungs. The blood goes through the lungs through the pulmonary capillaries. The red blood cells get rid of oxygen in the systemic capillaries and pick up carbon dioxide.

Link --> Video https://www.youtube.com/watch?v=xEHGIRpGyh4

Genre --> Science

Readability Level --> N/A

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How Red Blood Cell Carry Oxygen and Carbon Dioxide, Animation

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Red blood cells transport oxygen throughout the body. They are round disks with a concave middle to better help them be able to transport oxygen. They are made inside of the bone marrow.

Link --> Website https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentID=34&ContentTypeID=160

Genre --> Science

Readability Level --> Basic

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Red blood cells carry fresh oxygen throughout the body. This is important to your health.

Red blood cells are round with a flattish, indented center, like doughnuts without a hole. Your healthcare provider can check on the size, shape, and health of your red blood cells using a blood test.

Red blood cells at work

Hemoglobin is the protein inside red blood cells. It carries oxygen. Red blood cells also remove carbon dioxide from your body, transporting it to the lungs for you to exhale.

Red blood cells are made in the bone marrow. They typically live for about 120 days, and then they die.

Nutrition and red blood cells

Foods rich in iron help you maintain healthy red blood cells. Vitamins are also needed to build healthy red blood cells. These include vitamins B-2, B-12, and B-3, found in foods such as eggs, whole grains, and bananas. Folate also helps. It is found in in fortified cereals, dried beans and lentils, orange juice, and green leafy vegetables.

Illnesses of the red blood cells

Most people don't think about their red blood cells unless they have a disease that affects these cells. Problems with red blood cells can be caused by illnesses or a lack of iron or vitamins in your diet. Some diseases of the red blood cells are inherited.

Diseases of the red blood cells include many types of anemia. This is a condition in which there are too few red blood cells to carry enough oxygen throughout the body. People with anemia may have red blood cells that have an unusual shape or that look normal, larger than normal, or smaller than normal.

Symptoms of anemia include tiredness, rapid heart rate , pale skin, feeling cold, and, in severe cases, heart failure. Children who don't have enough healthy red blood cells grow and develop more slowly than other children. These symptoms show how important red blood cells are to your daily life.

These are common types of anemia:

Iron-deficiency anemia. If you don't have enough iron in your body, your body won't be able to make enough red blood cells. Iron-deficiency anemia is the most common form of anemia. Among the causes of iron deficiency are a diet low in iron, a sudden loss of blood, a chronic loss of blood (such as from heavy menstrual periods), or the inability to absorb enough iron from food.

Sickle cell anemia. In this inherited disease, the red blood cells are shaped like half moons rather than the normal indented circles. This change in shape can make the cells "sticky" and unable to flow smoothly through blood vessels. This causes a blockage in blood flow. This may cause acute or chronic pain. It can also lead to infection or organ damage. Sickle cells die much more quickly than normal blood cells-in about 10 to 20 days instead of 120 days. This causes a shortage of red blood cells.

Normocytic anemia. This type of anemia happens when your red blood cells are normal in shape and size, but you don't have enough of them to meet your body's needs. Diseases that cause this type of anemia are usually long-term conditions, like kidney disease, cancer, or rheumatoid arthritis.

Hemolytic anemia. This type of anemia happens when red blood cells are destroyed by an abnormal process in your body before their lifespan is over. As a result, your body doesn't have enough red blood cells to function. And, your bone marrow can't make enough to keep up with demand.

Fanconi anemia. This is a rare inherited disorder in which your bone marrow isn't able to make enough of any of the components of blood, including red blood cells. Children born with this disorder often have serious birth defects because of the problems with their blood and may develop leukemia.

Medical Reviewers:

# data[].attributes.attachment_link.description
Red blood cells carry fresh oxygen throughout the body. This is important to your health. Red blood cells are round with a flattish, indented center, like doughnuts without a hole. Your healthcare provider can check on the size, shape, and health of your red blood cells using a blood test.