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| Human heart. Gray's Anatomy, 1918 |
Here is an outline and links to the current heart and cardiovascular system-related learning guides currently available at Just Facts-Long-lasting Curriculum.
The basics on the circulatory system are in this other post.
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| Photo by Figiu, Wikimedia |
Research has shown again and again that antioxidants are beneficial to the human body. But it's really about the buzz word "antioxidants". It seems like some new food or concept, but antioxidants are just vitamins and minerals - something your parents kept telling you to eat as a kid!
Antioxidants are chemicals that protect cells from free radicals, atoms formed by some chemical reactions with oxygen (like the oxidation of low density lipoprotein, the LDL form of cholesterol), which can occur naturally or in response to environmental exposures to toxins, such as cigarette smoke. Antioxidants are usually found in foodstuffs (Nuts, grains, fish and poultry, green leafy veggies, fruits) and include several vitamins, including vitamin A, E, and C, as well as lycopene, lutein, and selenium. Increased intake of antioxidants is thought to protect against a number of disorders, including heart disease and cancer, and recent research has shown potential for protection from stroke. However, supplementation and dietary intake appear to offer differential effects with supplementation not providing the same benefits.
A 2000 study published in the American Journal of Clinical Nutrition, which examined antioxidant intake and stroke mortality in more than 34,000 postmenopausal women, found that vitamin E, acting as an antioxidant, may protect against death from stroke, but only if ingested via food. In 2011, a study published in the American Heart Association journal Stroke found that a greater total dietary antioxidant intake reduced stroke incidence in more than 36,000 peri-menopausal and post-menopausal women, regardless of cardiovascular disease status. Women without cardiovascular disease had a 17 percent lower risk of stroke, and women with cardiovascular disease had a 45 percent lower risk of hemorrhagic stroke. Approximately half of the antioxidants ingested by the women in the study were from fruits and vegetables, but the other half was from a variety of foods including grains, tea and chocolate .
Findings in men are not as prevalent, or as significant. Stroke is sometimes categorized in the broader category of cardiovascular disease. One study published in the journal Stroke in June 2011 looked at antioxidant intake and cardiovascular disease in Asian men and women, specifically in Japan. The only significant findings were in women – vitamin C decreased the risk of mortality from cardiovascular disease. However, a 2000 study published in the Stroke did find that dietary beta-carotene intake (the precursor to vitamin A) decreases the risk of stroke in male smokers.
Supplements may not show the same benefits because they focus on a single vitamin or antioxidant. The beneficial effect is most likely caused by the interactions between antioxidants and/or their cumulative effects. Clinical trials found that supplementation may work in those with increased levels of oxidative stress, perhaps by boosting the free radical scavenging process, but that those with normal oxidative stress levels benefit most from dietary intake.
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| Medical illustration by Patrick J Lynch |
Heart disease consists of a number of conditions that affect the heart, including coronary artery disease, congestive heart failure, and hypertension. The early stages of these heart diseases are different, but they have similar effects on the body if left untreated – heart failure.
Coronary artery disease is what most people mean when they say “heart disease”. This condition results from the accumulation of fatty deposits, called plaques, in the arteries bringing blood to the outer wall of the heart muscle. These plaques gradually block the blood’s pathway in the vessel, preventing oxygen and nutrients from getting to a portion of the heart (called ischemic heart disease).
Atherosclerosis, which can be caused by high cholesterol, is one underlying cause. Plaque formation causes other kinds of heart disease, too, such as aneurysms, and the condition is exacerbated by hypertension. Because of this underlying association, high cholesterol levels are one early stage of coronary artery disease.
Sometimes there are no other signs or symptoms that the coronary arteries are being blocked. A person can have a heart attack or even sudden cardiac death without warning. However, in many people, as the arteries become clogged and the amount of oxygen getting to the muscle decreases, pain may be felt. These chest pains are called angina. The earliest onset of angina is stable angina – shortness of breath, chest pressure, and sweating upon exertion – and it is not yet to the stage of permanently damaging the heart muscle. A test is available to determine the extent of artery blockage in individuals with suspected stable angina in order to prevent unstable angina (the symptoms occurring at any time) and the unpredictability that brings in regards to heart attack or heart failure, but research in 2008 found that it is greatly underused.
Hypertension is the presence of consistently high arterial blood pressure – so the earliest stages of this disorder involve elevated blood pressure readings. A disorder known as pre-hypertension (blood pressure between 120/80 mmHg and 139/89 mmHg) is now recognized by medical professionals as a way to identify patients who are likely to develop hypertension if something is not done to stabilize their blood pressure. Pinpointing at-risk individuals early is key because hypertension, which is known as the “silent killer”, generally does not have any symptoms until damage occurs to the heart.
A number of mechanisms are involved in the development of this heart disease depending on the individual, as the disease can be genetic or diet and lifestyle related – cigarette smoking, high cholesterol, a family history of the disease, diabetes, obesity, lack of exercise, and high salt intake have all been linked to high blood pressure. It is also an age-related disorder because over time the body’s regulatory functions become less efficient. Research is still trying to determine why hypertension is so prevalent among the elderly.
Congestive heart failure occurs when the heart is not working properly. It is due to damage from other heart diseases, such as ventricular hypertrophy caused by hypertension or scarring caused by heart attacks. Blood begins to back up and fluid swells the tissue spaces (called edema, and thus the term “congestive”). The lack of blood flow can cause pooling in the extremities (swollen ankles, hands, or feet) and fatigue. Once shortness of breath and regular coughing occurs, the disorder is past the early stages.
In addition to the signs mentioned above, the early stages of heart disease can include cyanosis, palpitations, and fainting.
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The high proportion of cocoa solids in dark chocolate bestows the treat with some of the healthier properties attributed to the cacao bean. Research has shown that flavinoids in cacao help prevent blood clots by affecting platelet function, and flavan-3-ols in the chocolate can lower blood pressure. More recent research has shown that catechins (epicatechin specifically) can help limit the damage caused by stroke.
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| Source: Patrick J. Lynch |
Genetic testing opens the doors to personalized medicine - before receiving treatment a doctor can determine if you will respond to the treatment, if you are even at risk for particular diseases the treatment will try to prevent, and whether you might have side effects worth avoiding.
Cardiovascular disease affects tens of millions of people in the U.S. alone - as coronary artery disease, hypertension, and angina, atherosclerotic plaques and miscommunicating hormones wreak havoc on the body, leading to heart attack, stroke, and other potentially fatal consequences.
In recent years, the door to genetic testing to aid in the treatment and prevention of these disorders has made its way to public use. Tests are being fine-tuned to determine a person's genetic risk for cardiovascular disease, genome-wide screening is highlighting susceptibility and treatment options, and a test can tell if chest pain is caused by current heart disease - allowing doctors to better decide who needs an angiogram, avoiding the invasive test in those who may have other reasons for the pain.
Source: Trounce, CC2.5SA license
Responsiveness to clopidogrel, sold under the brand name Plavix, is an issue for some patients who undergo anti-platelet treatment to prevent heart attack and stroke. Particularly susceptible are patients who receive the drug to prevent clotting and embolism after coronary stenting. Approximately 30 to 40 percent of people have a genetic mutation that makes them unresponsive to clopidogrel treatment. In 2009, Scripps Health began offering, for the first time in the US healthcare arena, a genetic test for patients undergoing coronary stenting to determine upfront whether they will be nonresponsive to anti-platelet treatment with clopidogrel.
Clopidogrel is metabolized by the cytochrome P450 (CYP) enzyme family. This metabolism is necessary for activation of the molecule and its anti-platelet effects. Patients with genetic variants of CYP2C19 (known as CYP2C19*2, CYP2C19*3, and so forth) have reduced enzyme activity and, accordingly, reduced activation of the drug. Scripps patients undergoing coronary stenting are tested by Quest Diagnostics for CYP2C19 variants that may affect clopidogrel responsiveness, allowing physicians to choose other anti-platelet drugs (such as prasugrel or ticagrelor) or to adjust dosage to the best benefit of the patient.
Some feel that this testing was debuted too soon. Research is still indicating other potential genes involved in treatment response, including controversial findings regarding PON-1, which encodes the paraoxonase-1 enzyme. The December 2010 findings that PON-1 is the enzyme responsible for bioactivation of clopidogrel have been refuted by more than one study, and CYP2C19 involvement supported. Experts consulted by Heartwire in October 2009 upon Scripps’ announcement felt that platelet function tests were necessary companions to genetic testing at this stage of the research on clopidogrel responsiveness. A number of companies now offer tests similar to Quest's.
In March 2010, the U.S. Food and Drug Administration (FDA) required a warning on Plavix to warn patients that a portion of them may be poor metabolizers of the drug. The warning also reminds health care provides that CYP2C19 genetic tests are available to aid in treatment planning. 25 million prescriptions were written for the drug in 2008 according to MedPage Today, leading to a great number of genetic tests. Some experts feel that, at best, the testing will aid in researching more appropriate dosing of the drug among those with genetic variants.
According to Heartwire in June 2010, the American Heart Association and American College of Cardiology do not recommend genetic testing as a determinant of therapy. They issued statements that urged care givers to follow current prescribing guidelines. The chair of the joint committee that issued the statement reiterated that the alternative drugs lack the track record of clopidogrel, and others urge platelet function tests in conjunction with genetic testing to ensure successful treatment planning that benefits the patient.
Fibric acid derivatives, or fibrates, are drugs prescribed to prevent heart disease by lowering triglyceride levels, though they are known as "cholesterol-lowering drugs", they are antilipemic agents. The drugs lower triglyceride levels as much as 25 to 50 percent according to WebMD, mainly by inhibiting the production of very low density lipoprotein (VLDL) in the liver and speeding up the removal of triglycerides from the blood. Lipoproteins transport insoluble fatty substances in the blood, including cholesterol and triglycerides; VLDL is the triglyceride-rich fraction. Triglycerides are fatty substances made up of three fatty acids and found in vegetable oil and animal fats. They play an important role in metabolism as they provide twice as much energy as carbohydrates and protein.
High circulating levels of triglycerides (hypertriglyceridemia) have been linked to atherosclerosis and heart disease, specifically the risk for coronary artery disease, and very high levels (>1000 mg/dl) can cause painful inflammation of the pancreas called pancreatitis. Fibrates are used to prevent pancreatitis and in conjunction with lifestyle changes (a low cholesterol and low-fat diet, exercise, smoking cessation) and statins to lower cholesterol. Fibric acid derivatives can not lower low density lipoprotein (LDL, also known as "bad" cholesterol) levels on their own, though they can increase high density lipoprotein (HDL, so-called "good" cholesterol) levels as much as 10 to 35 percent according to WebMD.
Fibrates activate peroxisome proliferator-activated receptors, known by their acronym PPAR, a group of intracellular receptors that activate the transcription of proteins used in lipid metabolism. Fibric acid derivatives mainly affect PPAR alpha, which is present in the liver and other tissues that metabolize fatty acids and is also involved in the inflammatory response in the blood vessel wall, an event associated with atherosclerosis. Fibrates are pharmacologically related to anti-diabetic drugs that also act on certain subtypes of PPAR. Fibrates in the United States include Lopid (gemfibrozil) and Tricor (fenofibrate). Gemfibrozil has been shown to decrease the risk of heart attack in individuals with coronary artery disease and low HDL levels.
Most patients tolerate fibric acid derivatives well, but like any other pharmaceutical treatment they can have side effects. Gastrointestinal pain and discomfort, headache, and gas or heartburn are common, but a doctor should be contacted if muscle pain, nausea or vomiting, fever, weakness, severe abdominal pain, or signs of allergy (hives, trouble breathing, swelling) occur. Patients on fibrates also have an increased risk of gallstones, which are small, hard accumulations of cholesterol in the gall bladder. Fibrates may alter the function of other medications, so your doctor should be aware of all other prescriptions and over the counter drugs you take.
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| Clogged artery. Source: Wikimedia |
Triglycerides are often measured alongside cholesterol on lipid panels. Like cholesterol, triglycerides are a type of lipid stored in the body and circulated in the blood in the form of lipoproteins. “Bad” diets high in calories or containing too many carbohydrates or fats increase triglyceride levels.
Extra calories that are not used right away for energy are converted to triglycerides, which are stored in fat cells. “Bad” diets high in calories or containing too many carbohydrates or fats increase triglyceride levels. The normal level of triglycerides in the blood is currently accepted to be less than 150 mg/dL in the United States, equivalent to 1.7 mmol/L in Canada and Europe, but the exact range may vary by age and sex. A higher than normal triglyceride level is not a disorder on its own, but it is a risk factor that should be addressed to avoid health issues.
Triglyceride levels up to 200 mg/dL are considered borderline high, and more than 200 mg/dL are high. As explained by the American Heart Association, individuals with heart disease or diabetes tend to have higher than normal triglyceride levels, as well as individuals who are overweight or obese, physically inactive, smoke cigarettes, excessively consume alcohol, and eat a diet consisting of 60 percent or more carbohydrates. When combined with high cholesterol, the triglyceride levels can speed up the development of atherosclerosis, which increases a person’s risk for heart attack and stroke. Even borderline high levels are a risk factor for metabolic syndrome, which increases the risk of heart disease and diabetes. Peripheral artery disease is also a concern.
High triglycerides are considered a lifestyle-related risk factor and can be manipulated by diet and exercise, as well as abstaining from tobacco use and limiting alcohol consumption. Avoiding high-sugar foods is also recommended by the AHA. Lowering cholesterol and avoiding foods high in cholesterol can also aid in reducing triglyceride levels. Omega-3 fatty acids (found in fish) can help reduce total lipids.
Triglyceride levels higher than 500 mg/dL are considered very high. In addition to the problems associated with high levels, very high levels may lead to complications such as accumulation of fat in the liver (fatty liver disease) and inflammation of the pancreas (pancreatitis). Medication may be used to lower the triglyceride levels when lifestyle changes are not enough. Common medications include fibrates, nicotinic acid (niacin), and high doses of omega-3.
Individuals with genetic abnormalities that lead to triglyceride accumulation may hit levels as high as 1000 mg/dL. Some individuals who suffer from diabetes, severe obesity, or alcoholism may also have levels this high. Familial hypertriglyceridemia affects 1 in 500 people in the United States and is caused by an autosomal dominant mutation. The condition is generally not associated with increased cholesterol levels, but the individuals are at risk for hyperglycemia and diabetes, very high VLDL levels, obesity, hyperinsulinemia, pancreatitis, and coronary artery disease. These individuals often are counseled to avoid alcohol and to follow a strict diet. Medications may be used when addressing lifestyle factors and underlying problems (obesity, diabetes, hypothyroidism) does not reduce levels.
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| Common Lipids. Eoin Fahy, GNU license |
Cholesterol is a fatty, waxy substance made by the human body. It is also present in some foods and a necessary molecule used by various tissues in the body to make certain vitamins and hormones, but high levels of cholesterol in the blood can lead to deposition in the arteries and some tissues, causing blockage (atherosclerosis) and disease over time.
Triglycerides are free fats measured on lipid panels alongside cholesterol. High levels indicate circulating lipids that can accumulate in plaques with cholesterol. The guidelines noted below recommend keeping triglyceride levels below 150 mg/dL (milligrams per deciliter, the standard measure used in the United States).
Lipoproteins are molecules made of fat and protein. These molecules carry cholesterol around the body, allowing it to pass in and out of cells as needed. A standard lipid panel measures two types of lipoproteins, LDL and HDL. LDL stands for low density lipoprotein (or “bad” cholesterol), and HDL represents high density lipoprotein (or “good” cholesterol).
Based on guidelines set by the National Institutes of Health National Cholesterol Education Program, the optimum LDL value is less than 100 mg/dL, and HDL values should be above 60 mg/dL. However, individuals with no other risk factors for heart disease can consider an LDL level between 100 and 130 mg/dL acceptable, and individuals with a family history of cholesterol-related disease should aim for less than 70 mg/dL. Ideally, the LDL to HDL ratio should be 3.5 to 1, with recommendations to maintain it no higher than 5:1.
Though not part of the standard lipid panel, other lipoproteins are sometimes considered in cholesterol evaluations, particularly lipoprotein(a) and VLDL.
Lipoprotein(a) is LDL with an apolipoprotein A molecule attached. Recent research has found that high levels of this molecule in the blood are a risk factor for heart disease. A value of less than 30 mg/dL is generally considered the target, though the normal range will vary by laboratory. For VLDL (very low density lipoprotein) the target range is 5 ro 40 mg/dL. However, VLDL is usually determined as a percentage of the triglyceride levels and not measured directly.
The last measure included on lipid panels is total cholesterol, a measure that takes into account all forms of cholesterol in the blood. The total cholesterol level should ideally be less than 200 mg/dL.
Researchers are expecting that combined drug therapies will help reduce heart disease-associated mortality. The ONTARGET trial looked at an angiotensin receptor blocker and ACE inhibitor (telmisartan and ramipril), traditionally anti-hypertensive drugs, in the treatment of cardiovascular disease in the absence of heart failure. The ONTARGET study findings were published in the April 10, 2008 issue of the New England Journal of Medicine.
