There are many different causes of heart failure with a normal ejection fraction The two most common, a lifetime without any physical conditioning and the long-term effects of high blood pressure, have no specific treatment beyond blood pressure control, physical rehabilitation and the judicious use of diuretics (fluid medicine). The usual armamentarium of drugs to assist the heart’s efficiency does little to alter the course of illness, making this form of heart failure most vexing. Recently, an illness, once thought to be a terribly rare cause of heart failure with normal ejection fraction, has proved to be awfully common and appears to be treatable.
The illness, called Amyloidosis, is characterized by deposition or silting of unused protein in between the cells of various organs. Proteins are normally made, used and recycled. When that process is disturbed, unrecycled protein may accumulate and deposit in between cells. In the heart, the protein leaves little room for cells to stretch out and the walls of the heart become thick and stiff. Blood pressure in the veins of the body and lungs must stay high to force blood inside of the heart. The result is swelling in the ankles and trouble breathing or a heart that just pumps less blood.
The first recognized type of Amyloid was due to cast off and unused antibody from an immune system that was, for various reasons, in the habit of overproducing. This type of amyloidosis is relentlessly progressive and difficult to treat. Fortunately, it is uncommon and amyloid heart disease was felt to be rather rare. In fact, more than one type of discarded protein can cause amyloidosis and amyloid heart disease is not so rare at all.
Transthyretin is a protein similar to the ubiquitous albumin. Its function is mainly to carry other substances, like thyroid hormone and Vitamin A, on their travels through blood. Transporting thyroid hormone and retinoic acid (Vitamin A) gave rise to the name. Abnormal transthyretin or its abnormal metabolism may result in accumulation, mostly in the heart or peripheral nerves. This form of amyloidosis can vary in severity. Unlike its more malignant cousin, it may be quite subtle. More importantly, it is far more common and may be responsible for as much as 5% of heart failure with normal ejection fraction. Since heart failure with a normal ejection fraction represents ½ of the people with heart failure and the prevalence of heart failure is rapidly climbing, that 5% represents a lot of people.
Part of the problem with discovering amyloidosis is that, in years past, the heart had to be biopsied to make a diagnosis. Fortunately, technology now allows the proteins that deposit in the heart to be seen or suspected without a biopsy. The first observation that raises suspicion is abnormal thickening of the heart wall seen on an echocardiogram. In and of itself, a thick heart wall is weak evidence for a diagnosis of amyloidosis. About ½ of all people with heart failure and a normal ejection fraction, have thick walls. However, about 10% of people with heart failure, normal ejection fraction and thick walls may have amyloid. (1)
Why does this matter?
First, testing to detect amyloidosis without necessarily requiring a biopsy of the heart is available. Images from an MRI can reveal evidence of abnormal protein in the heart, if the problem is severe. Recently, a technique called T1 mapping, which is more sophisticated than just a picture, has been developed. T1 mapping may be able to detect a problem very early, perhaps even before symptoms become severe. In addition, the substance used to perform a nuclear medicine bone scan also loves the proteins stuck in between heart cells. A bone scan is a simple and easy test to perform. In essence, if the heart muscle appears thickened, a nuclear bone scan that shows the heart is good evidence that amyloidosis may be present. Both tests may make detection of this cause of heart failure possible at much earlier stages, where treatment may actually be able to reverse the process to some degree.
Not only has detection been made easier, but also Transthyretin-related Amyloidosis may now be treatable. Tafamidis is a drug that locks on to transthyretin so that it is processed more slowly, allowing it to be processed properly. In a recently reported test of the drug, Two hundred sixty-four people with proven Transthyretin amyloidosis of the heart were treated and followed for 2.5 years. Tafamidis treated people enjoyed a substantial reduction in mortality, compared to 177 of their peers treated with placebo.(2) Importantly, the observations made in the trial suggest that earlier diagnosis and treatment have greater effect.
The success of Tafamidis in treating this form of cardiac amyloidosis will be a sea change in the approach to people troubled by heart failure with normal ejection fraction. If the success of Tafamidis is confirmed, a “bone scan” may become a commonly performed test of the heart.
1. Castaño A, Bokhari S, Maurer MS. Unveiling wild-type transthyretin cardiac amyloidosis as a significant and potentially modifiable cause of heart failure with preserved ejection fraction. European Heart Journal. 2015;36(38):2595-7.
2. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. New England Journal of Medicine. 2018. 10.1056/NEJMoa1805689
Heart failure is a general term for a group of symptoms including fatigue, swelling and difficulty breathing. Each of these symptoms may have any number of causes. When evidence points to the heart as a root cause, the constellation is known as heart failure. The heart’s failure is its inability to circulate enough blood to support normal daily activities without relying upon help from various sources within the body. Its inability to perform is the source of fatigue and its calls for help produces many of the other symptoms.
Heart failure as a diagnosis is about as specific as headache. Without a genuine reason for the heart’s failure, no speculation can be offered as to its repair. The first step toward a more specific diagnosis classifies heart failure using the most readily available measurement of the heart’s function, the ejection fraction (EF). The fraction of blood leaving the main pumping chamber (left ventricle) during each heartbeat is called the ejection fraction. Heart muscle dysfunction causing heart failure is broken down into two large categories, heart failure with an ejection fraction below normal, suggesting weakened or disadvantaged muscle, and heart failure with the ejection fraction preserved.
Of course, the heart may be inefficient because the heartbeat is mistimed or because of a broken part, like a heart valve. In these instances, heart failure is mentioned secondarily because the diagnosis is apparent in the arrhythmia or the broken part. When the muscle is the source of dysfunction, the classification scheme using EF helps to orient physicians and caregivers to the tests that may find a cause and the treatments that may be most effective.
Historically, heart muscle was viewed in a very simple fashion, like all muscle, as a tissue that shortens on command. Any failure of the muscle must be apparent in a change in its ability to shorten. As a result, heart failure was under recognized. Blood tests and a number of other techniques have improved capacity to recognize when symptoms like shortness of breath are coming from the heart. Therefore, an increasing number of people are being told that their breathlessness is coming from the heart even though the “strength,” as judged by the ejection fraction, appears to be “normal”. A muscle may function poorly if it is weak, if it cannot relax, or if the support structure that houses muscle cells functions improperly. We now know that almost ½ of people with symptoms believed to be heart failure have a preserved ejection fraction.
This entity, often referred to with the awful abbreviation HFpEF, is very real, difficult for many of us to understand and equally difficult to treat. Fortunately, as understanding improves, the ability to recognize measurable abnormalities that correspond to symptoms is improving, for example using exercise testing with concurrent Doppler echocardiography to estimate blood pressures in different parts of the circulation.
Our bodies are large and complex. Cells are not concerned with complexity. They are simply needy. The broad sweeping narrative of normal cardiovascular function is delivery that is prompt, proportional and predictable. The normal heart and arteries deliver, regardless of circumstances and with little notice. Simple. There are, however, a few details.
James M. Wilson, MD The Heart Beat Houston MDs Neurology: 713-790-1775 Cardiology: 832-336-1530 Fax: 713-790-1605 Normal Cardiovascular Function Our bodies are large and complex. Cells are not concerned with complexity. They are simply needy. The broad sweeping narrative of normal cardiovascular function is delivery that is prompt, proportional and predictable. The normal heart and arteries deliver, regardless of circumstances and with little notice. Simple. There are, however, a few details. The Arteries The average cell needs to be bathed and refreshed constantly. Cells enjoy just such a bath that moves in a gentle to and fro, sent out from arteries and collected by veins. A heartbeat lasts a very short time, only about 1/5th of a second. In that time, roughly 4 tablespoons of blood are sent out to the arteries for delivery and the pressure in the arteries rises from 70 to 105 mmHg. Were arteries and veins simple plumbing, every bit of blood in the body would be required to move in unison in the short time of a heartbeat. The strength required to accomplish this feat would be so great that a human heart would have to have the strength of a bull. Arteries stretch and rebound. They are smarter than plumbing.
In the short time of a heartbeat, blood is shoved into the largest artery (Aorta). Blood already sitting there is pushed forward. At the same time, the artery stretches out to make more room. Instead of moving all of the blood in unison, from the heart to the smallest artery, pressure builds. Afterward, while the heart is relaxed and refilling, blood continues to be jostled about by arterial walls that are like a stretched spring. Up and down the line of arteries, stretched walls vibrate their encouragement to keep blood moving. All of the work moving blood does not have to be done in the blink of a heartbeat. Because of artery's rubber-like behavior, much of it the work accomplished during the time in between.
There is an aphorism about organizations. Sergeants run the army. Nurses run the hospital and secretaries run the world. Arterioles run the circulation. (Figure 1) They are the faucets governing flow and respond to strategic direction from nerves and hormones. For example, adrenalin makes many arterioles tighten severely so that blood will be diverted to where it is most needed. However, most of the decisions about blood flow to a tissue are made locally, without direction from nerves and hormones. Arterioles are the entry, controlling flow into the large, thin walled network of capillaries. Sitting upstream from all of the cells that they supply, arterioles can somehow sense how much blood is needed. Capillaries weep much of the fluid part of blood across their cheesecloth-like walls. The part of blood that can't cross the wall stays inside the vessel and moves along to a pool of low-pressure venules, the microscopic beginnings of the veins. There, because of the lower pressure, fluid seeps back inside of the vessel. That fluid contains waste from the cells.
Tissue waste that includes Carbon Dioxide (CO2), adenosine and a few other things that are carried with the fluid back into blood vessels make microscopic veins relax. Relaxed veins grow larger and blood speeds away more quickly, as though running down a steeper hill. Easier out from the veins means faster flow in the capillaries and, in turn, faster flow in the arteriole. The lining of the arteriole feels the tug of the torrent and releases Nitric oxide. Nitric oxide relaxes the wall of the arteriole, opening the channel for more blood to pass. (Figure 2). This process is called autoregulation.
Large arteries absorb and distribute the blow from the heart while small arteries regulate where and how much blood may pass. Changing either of these behaviors can cause disease. More commonly, these aspects of artery function are changed in the course of a disease. For example, high blood pressure has many causes. In any individual with high blood pressure, there is rarely a single fault, but many combined. Arteries, both large and small, adapt to elevated blood pressure by increasing stiffness and thickness of their walls. The result is perpetuation of rising blood pressure regardless of its root cause(s). Meanwhile, many of the medicines that lower blood pressure act by changing either stiffness of large arteries, the opposition of small arteries or both.
Our heart is actually two muscular pumps joined side-by-side and twisted together like a work from Escher. The two pumps are referred to as right and left for simplicity. On each side, an upper chamber (atrium) receives blood from veins and a lower chamber (ventricle) discharges it with enthusiasm into an artery. There are two sets of blood vessels connected to the heart. Both sets of vessels include both arteries and veins.
A large artery called the aorta carries blood away from the heart and on through all the needy tissues, such as the brain, muscles, intestines and kidneys. The blood collects in large veins (Vena Cava) and returns to the heart, but to the part that will send blood to the lungs. The vena cavae (there are two) is connected to the right atrium, where blood rests briefly before moving to the ventricle for discharge to the lungs. The second set of blood vessels carries blood away through the pulmonary artery, travels through the lungs and returns in pulmonary veins. Pulmonary veins are attached to the left atrium where blood rests briefly before moving to the ventricle for discharge to all points distal. Between each of the atria and their ventricles, and between each ventricle and its artery, is a valve that ensures blood will only move in one direction. Together, both sets of arteries and veins make a grand loop in a figure eight, with the heart at its center: Aorta to Vena Cava to Heart to Pulmonary Artery to Pulmonary Vein to Heart and repeat. The left ventricle is usually the principle focus of interest as the pump supplying the body. It moves blood forcefully in increments, one-quarter cup with each beat. (Figure 3)
Individual heart muscle cells function simply. They shorten and relax. Laid end to end, the tiny contraction of each cell adds up to a movement of some distance. Laid side by side, their contraction has leverage that generates pressure. Archimedes claimed that, given a lever and a place to stand, he could move the world. For the heart, the shape of the pumping chamber and the thickness of the heart muscle are the lever and the place to stand. Two familiar animals offer examples of how form affects function. The frog lives life mostly prone, often in water, and minimally challenged by gravity. Its left ventricle is thin-walled and spherical, a mostly end-to-end orientation made to move large amounts of blood at low pressure. In contrast, the giraffe has a head sitting atop a long neck. This neck provides reserved seating for the finest dining, but keeps the brain at dizzying heights. In order to maintain blood flow to the brain, the heart must provide sufficient pressure to overcome the effects of gravity. As a result, its left ventricle is thick-walled with a chamber, shaped like a cylinder that is good for gripping. Although ill prepared to move large quantities, it is a very efficient pressure generator. The design of the human left ventricle lies somewhere between the cylinder and the sphere, resembling an American football.
Configuration (shape combined with muscle thickness) and the intrinsic ability of individual cells determines the heart's leverage for generating pressure and capacity to move large amounts of blood. However, each cell of the heart must follow direction. Should each tiny muscle cell act alone, the result would be a heart in wriggling chaos, without moving any blood.
Arm and leg muscles receive direction from the brain. Heart muscle cells receive direction from their neighbor. A small area of the right atrium called the sinus node awakens approximately 100 times each minute. Its awakening is a change in its electrical charge that spreads like the chime from a clock tower. As each cells feels the change, its machinery contracts even as it begins a rapid effort to return to normal. The sinus node has no other responsibility save to initiate the heartbeat.
The lights come on in the sinus node and the electrical charge moves through atrial muscle cells like a brush fire. Ventricles do the real work of sending blood out of the heart. Their contraction depends upon the spread of the same electrical charge that went through the atria. Although, the cells of the atria and ventricles lie in close proximity, they do not communicate directly. A point at the very center of the heart, where all four chambers are adjacent to one another, contains a small group of cells that bridge the communication gap. Like the sinus node, this is their only purpose. This small group of cells is the communication ?junction? between the atria and the ventricles, also known as the AtrioVentricular (AV) node. The junction was not designed for speedy communication. Its cells communicate with one another like a large group of people passing a message through a crowded room. The time required for the junction to pass along a message creates a pause between the awakening of the atria and the real work that follows in the ventricles.
Within the ventricles there are so many muscle cells that communication, one to another, would take a very long time to make all of them move. The heart awakened in such a fashion would only suggest blood move on, rather than ejecting it. Therefore, a few muscle cells, like the cells of the sinus node and junction, have forsaken contraction and live only to pass along a message. They are arranged in long filaments. Groups of these cells, like communication cables, are called fibers. Near the junction, fibers are tightly clustered into bundles, one to the right ventricle (Right Bundle Branch) and another to the left (Left Bundle Branch). Out near the intended point of communication with working muscle, groups of these cells are called Purkinje fibers. This communication network spreads the electrical charge so quickly that all points of the ventricle move almost simultaneously. The effect is like the coordinated movement of both hands together in a clap.
Although the human heart sees 1,800 gallons of blood going by every day, it can't drink a drop. It must be supplied by its own set of arteries. These arise from the aorta, very near its attachment to the left ventricle. From their origin, the arteries that feed the heart immediately drop down onto its surface, giving the appearance of a crown, or corona, at the base. Thus, they are known as the coronary arteries. There are two coronary arteries, one for the left side of the heart and one for the right side. They don't distribute exactly to the left and right sides and they vary from person to person, like fingerprints. (Figure 4)
Before technology extended the capacity of observation, the workings of the body were understood through the theory of humors. Energy, animation and all the stuff of life was governed by varying mixtures of basic humors. The humors were endowed with specific powers and characteristics. They could be either hot or cold and wet or dry. Illness arose from imbalance. Their origins differed but the mixture came together in blood as the heat of life. The heat of life was understood to penetrate and enliven all tissues. Altogether, given the limits of our senses and the information available at the time, the scenario is quite reasonable. In fact, some of the conceptual imagery persists today. Something that incites waste of one's vital heat makes the blood boil. Somehow snatching that vital heat away to stop the heart makes blood run cold. There is little doubt that blood carries the stuff of life. Our understanding of that stuff is just made more sophisticated by available technology. Blood is actually a mixture of about 1/2 saltwater with dissolved substances and 1/2 suspended solids. Suspended means separates when still. In a clear tube, the sunken part is mostly dark red and the top part as a clear fluid that is golden to straw-colored. The clear, golden part, called plasma, is full of salts and proteins with a specific job to do. The parts that sink are just too large to stay water-born while sitting still for any period. Most of the sinkable part is cells or pieces of cells that are big enough to be seen under a microscope.
The most abundant cell is the red blood cell. Its job is to carry oxygen, like a boxcar on a train carries cargo. Oxygen is necessary for most basic functions, most importantly harvesting energy from food. We use almost 8 ounces of oxygen every minute, but the amount that dissolves in water is very small. Red blood cells are packed with hemoglobin, a protein that is folded around an iron atom like a catcher's mitt. In its folds, oxygen sits comfortably, making the iron just a bit more red. Red blood cells are discoid and deformable, easing their movement through the crowed spaces of small arteries and capillaries.
Fewer in number but larger in size are a group of cells with no coloring. When mixed in with the red cells, they invisible to the naked eye. All alone, their lack of coloring leaves them appearing white. These white blood cells are responsible for the body's defense. Last of the visible elements is the platelet. Where all blood cells are made, in the bone marrow, a cell devoted to sealing wholes in blood vessels grows to a great size. Pieces of it break of to enter the blood stream and perform their function. These small cell remnants are like fragments of a shattered plate, giving them their name. (Figure 4).
Nature would invade and destroy with no mercy without the constant patrol of the immune system. It is amazingly complex, precise, and effective. Immunity is pervasive. It consists of cells and dissolved proteins found in every tissue. The system was once thought to be centered on a body fluid management system called the lymphatic system. Lymph is clear fluid. Along the system's pathways are small nodules that were referred to as lymph nodes. Lymph nodes are full of cells identical to roughly half of the white blood cells found in circulation. Stained and examined under a microscope, these cells have a large, round nucleus with smooth, blue surroundings. Their resemblance to the cells populating lymph nodes gave them the name lymphocytes. Although uniform in appearance, there are a great many types of lymphocytes. They are responsible for direction, coordination and some enforcement of the immune system.
One type of lymphocyte is responsible for making antibodies. Antibodies are water loving proteins found in plasma. They are capable of recognizing virtually anything foreign to the body. Where they attach, the enforcement of the immune system is targeted, including sequestration, removal and destruction. A separate white blood cell, found in circulation, is distinguished by a sandy or granular outer appearance and a nucleus that looks like splatter (shown in Figure 4). These are destructive enforcers called granulocytes. One other type of white blood cell looks like a lymphocyte, but is much larger. In blood, it is called a monocyte. Once out among tissues, it becomes even larger and performs all enforcement functions. In tissues it is called a macrophage. Immune function participates in several heart illnesses, most notably the disease of heart valves known as Rheumatic Fever. Macrophage behavior is very important to the development and progression of atherosclerosis.
A coagulum is the gelatin like mass that forms from blood held in a glass tube. The blood components that create a coagulum work in circulating blood to seal fissures or fractures in blood vessels. The coagulation system works like a magic glue that moves about, sealing only when and where necessary. Some fast acting, industrial strength adhesives or glues are made of components that are so reactive with one another that they are kept physically apart until needed. When mixed, the combination is activated to its working and final state. The proteins dissolved in plasma work in a similar fashion but do not have to be physically separated before their activation. Meanwhile, once changed to their final state, they are a bell that cannot be unrung.
The components that will become biological cement mingle constantly in flowing blood. If the system were to simply be turned on and allowed to react all over, we would become a large collection of gelatin very quickly. Fortunately, the system is tightly regulated.. Coagulation proteins are washed away if they have nowhere to sit. Unprotected, they are quickly disarmed. Platelets, the small bits of cells floating about, are a special sanctuary where the glue-making coagulation proteins can get together. After platelets attach to a break in a blood vessel, they can then link together. On the surface of these platelets, the clotting system turns into glue, like masonry mortar. The mass that forms is a blood clot. In a normally functioning vessel, a clot should not form. In order to keep the clotting system from performing its task, blood is kept moving in an orderly fashion; no breaks are exposed AND the surface of a healthy blood vessel helps to disarm any wayward proteins and platelets.
Atherosclerosis, the disease responsible for heart attacks, triggers the coagulation system by exposing the underbelly of artery walls. Events like heart attack and some forms of stroke begin with platelet attachment and progress from there. Although treatment for atherosclerosis frequently employs a medicine to blunt platelet function, the fault lies in the breakdown of the artery wall, rather than with the platelets.
Energy is trapped in food, thankfully. It can?t be burned like coal to run a steam engine. So, when energy is released from food, it must be harnessed in a very particular fashion. The parts of food used for energy are carbohydrate (sugar) and lipid. Sugar is a grab bag term for substances that have a specific type of construction. They dissolve easily in water; are generally sweet to taste; may be found in different forms in many types of foods, and have names that end in ?ose, like sucrose, fructose and lactose. The sugar in milk is different from the sugar in an apple or in sugar cane. Glucose is the sugar used by the body. Burning any fuel requires oxygen. Burning the body's fuel requires oxygen to be most efficient. However, glucose can be used to release energy without oxygen. This mechanism is fast, brief and very inefficient. It is like trying to warm a room with a match.
Lipid is a broad term that encompasses fats, oils, waxes and the like. However, in this discussion, any mention of lipids is in reference to fatty acids, triglyceride and cholesterol. A fatty acid is a long molecule with one end that likes to associate with water and an oily tail that is shaped like a pipe cleaner bent into a zigzag. The long oily tails are none to fond of water, but love one another. They are stored by attaching fatty acid to a sugar-like molecule called glycerin. There are only three places to add a fatty acid to glycerin. Therefore, the complex is called a Tri-glyceride. Dietary sources of fatty acid and triglyceride abound, including meat, dairy, and plant fats.
The liver coordinates energy storage and distribution. It processes triglyceride from the diet. However, it may also convert surplus glucose to fatty acid and attach surplus fatty acid to glycerin. Glucose is distributed easily because it is soluble in water. Fats float, making transportation through the watery bloodstream difficult. Therefore, the liver packages them in special capsules whose outside lining has an affinity for water. The capsules, called lipoproteins are complex. Mixed into the surface coating are a group of handles that cells use to recognize the lipoprotein and extract its contents. (Figure 6)
Cholesterol is a chain of carbon atoms folded into shapes instead of long oily tails. The shapes make cholesterol useful in the construction of hormones and cell membranes. Most of the body's cholesterol is made in the liver rather than being taken in through diet. However, like triglycerides, it interacts poorly with water and must be transported to cells in a lipoprotein capsule.
The capsules are named based upon where they land after a trip through a centrifuge. The force applied to blood placed in a centrifuge is enormous. Contents exposed to that force order themselves according to size and density, softballs at the top and golf balls at the bottom. The capsules that carry lipid out of the liver are large and fluffy. They have the very clever name, Very Low Density Lipoprotein (VLDL). After a tour of the body, VLDL gives away some of its triglyceride. It becomes the smaller, denser, Low Density Lipoproteins (LDL) that still has plenty of cholesterol. LDL continues to make deliveries and is eventually taken back by the liver. The smallest and densest capsule is called High Density Lipoprotein (HDL). HDL is sent from the liver virtually empty. Its task is to bring lipid to the liver.
Abnormal energy metabolism traps many of its components in circulating blood. Excess glucose impairs tissue function throughout the body. It may also attach itself to a variety of proteins, furthering its dysfunctional influence. Lipoproteins in excess accumulate where they do not belong. The attemps to clear them away is one of the driving forces behind the development of atherosclerosis and heart attack. This is a brief, general description of basic functions affecting and affected by the heart and arteries. Each function is important in the pursuit of basic health maintenance as well as understanding most of the common forms of heart disease.
In a sound sleep, with thoughts of sugar plums or a sandy beach dancing about in your head, a pain in the leg or the foot makes its presence known with high drama. The discomfort is sharp, knifelike and will not go away. The only hope for relief is to address the forcefully extended foot or the toes curled inward like a dying spider. Muscular cramping is a common malady. Almost two-thirds of us will report its presence at some point and one in five are so bothered that they bother someone else about it. Cramping is very different from another common malady, Restless Legs Syndrome. RLS is marked by discomfort or feeling ill at ease without standing, walking or otherwise moving the legs. Muscular contraction is not its source of discomfort. The phenomenon of nocturnal leg cramping is poorly understood and its cause is not known with certainty. During athletic endeavors, cramping occurs with muscle fatigue but this is not the same as the nighttime visitor. Electrical observation of muscle cramping suggests that the origin is most often in the nerves that command them. Although deficiency in calcium, magnesium or potassium may be marked by muscular symptoms or spasm, they are not implicated in the common nocturnal leg cramp. Medicines are often blamed but to date, the only strong evidence points to estrogens, intravenous iron and cancer treatments.
The list of suggested remedies for nocturnal cramping is long and includes, muscle relaxers (carisoprodol), the blood pressure medicines called calcium channel blockers (verapamil, diltiazem) and Quinine. Quinine is the magical component of the Peruvian bark and the source of bitterness in tonic water. It is the original antibiotic produced on a large scale and was used to treat malaria. In addition, happy accident found it to be a manipulator of biological electricity as well as boon to the muscular cramp. Of the medicines offered for cramping, Quinine is the only one proven effective but its potential for dangerous, even lethal side effects is such that it is best avoided. (1) Magnesium is one of the aforementioned parts of salts whose deficiency may cause cramping. It is necessary for every cell to function and depleted from the body by many medicines and illnesses. However, the fact that deficiency causes a problem does not mean that routinely taking extra will prevent the same problem is something else is at fault. Nonetheless, magnesium supplementation, which is not completely risk free, is often turned to as a cramping remedy. Thus was born the study.(2)
In a group of people complaining of nighttime leg cramps, will Magnesium supplementation affect their complaints?
In Israel, adults who reported at least four episodes of cramping in the previous two weeks were given either a magnesium oxide pill or a similar-looking placebo to be taken at bedtime for a period of 4 weeks. They recorded their symptoms. Ninety-four people participated. They were older, about 65 and six of ten were women. At the beginning, almost everyone had daily symptoms. At the end, almost everyone reported three fewer episodes each week and it made no difference if they were given Magnesium or placebo. Therefore, magnesium supplementation cannot be counted on to improve symptoms of nocturnal leg cramps. The authors pointed out that everyone improved suggesting that nocturnal cramping treatment may be subject to significant placebo effect.
Impact and analysis
If you have bothersome leg discomfort that impairs your rest, the first step is to talk to your doctor. He or she may recognize Restless Legs Syndrome or identify a medicine or metabolic disturbance as the source of the problem. RLS is very responsive to medical treatment. If muscular cramping is the cause, supplementing salt intake with magnesium or potassium, should only follow identification of a deficiency. In absence of such, magnesium clearly has no value and potassium may be dangerous. Curcumin, a component of the yellow spice, Turmeric has an abundance of anecdotal reports with no underlying rationale or trial evidence. Many physicians recommend, also with little evidence, specific muscle relaxers and calcium channel blockers. The only medication with evidence of usefulness, Quinine is also potentially dangerous and not recommended. Therefore, there is little to offer the cramp afflicted save reassurance, a bit of benign neglect and perhaps a recommendation to keep the legs warm at night.
Keywords: Nocturnal cramp, Magnesium
1. El-Tawil S, Al Musa T, Valli H, Lunn MP, Brassington R, El-Tawil T, et al. Quinine for muscle cramps. The Cochrane database of systematic reviews. 2015(4):Cd005044.
2. Roguin Maor N, Alperin M, Shturman E, et al. Effect of magnesium oxide supplementation on nocturnal leg cramps: A randomized clinical trial. JAMA Internal Medicine. 2017;177(5):617-23.
Why composition should take the place of weight.
The new addition to potboilers of how to lose 30 lb in 3 weeks or the one month cure for your risk of heart attack is that changing weight and complications of cardiovascular disease ride together.(1) As grabbers go, this is a winner and it could be the source of serious misunderstanding. It is not a mistake or fanciful finagling with numbers. The observation is real. It is meaningful. It raises a very important question about weight loss and diets but in no way suggests that lifestyle changes with weight loss in mind are bad.
Obesity is the problem for all seasons, linked to high blood pressure, diabetes mellitus, elevated cholesterol, sleep apnea as well as heart failure, atrial fibrillation and heart attack. The link to cardiovascular disease is such that body weight often takes center stage in efforts to treat illness.(2) From the association between body weight and the known risk factors for cardiovascular disease come estimates of the value of weight loss. Lose weight and blood pressure is easier to control. Risk factors improve. Therefore, it seems logical that virtually any effort that safely reduces body weight while maintaining essential nutrition is going to be valuable but there is a problem. A consistent observation from efforts to improve the lot of people with cardiovascular disease is that people with disease, who are on average heavier fare better over time.(3) The observation that heavy people get sick but sick, heavy people do better over time is referred to as the obesity paradox. When this thorny observation first attacked logic, a variety of explanations were offered but as yet, no one really knows why it is true, just that it is. Even faced with the paradox, most physicians do not question the need to reduce body fat when its known effects may be fueling identified vascular disease. However, it is possible that weight loss efforts may not provide the benefit that is expected of them. Specific regimens may lower weight without reducing fat. Worse, many diet and exercise regimens designed to address body weight often have brief success, only to see weight return, likely as fat.
In people left to their own designs, does weight that is frequently changing correspond to any difference in the chance of having a heart attack or other problems related to cardiovascular disease.
The source of information was a study done to record heart attacks and complications of cardiovascular disease in more than 9500 people testing different doses of a cholesterol-lowering medication. What the investigators did with the information was to pay attention to something that is usually ignored, how much body weight changed each time it was measured during the study.(1) Over a period of several years, most participants had some variation in weight from visit-to-visit. In about 10-15% of people, the weight swings averaged more than five pounds for each visit. The swingers had an increased risk of complications even when all other things were taken into account. There were several methods of describing how much weight varied between visits. Regardless of how the difference was portrayed, people whose visit-to-visit weight varied more than others, not just in one direction but the amount that it swung in either direction, had a greater chance of encountering difficulty.
The study discovered an association between changing weight and complications but it couldn't address the next question. Why? Did one cause the other or are they just two faces of some other underlying problem? There is no way to tell from the information available. The set up above would suggest that the answer is obvious, dietary recidivism changes body composition to more fatty over time driving vascular disease. However, as often as not, the obvious answer proves to be wrong when put to the test. While we wait for more information, the things to think about are, pay more attention to your waistline than your weight. One of the problems with something like obesity is to make it into a number. Exactly what does it mean to be fat? Is it too much weight, too much weight for age, for height or both? Your total body weight reflects muscle, bone, organs as well as fluid and fat. Changes in weight lasting more than a few days are usually due to a change in either fat or what is referred to as lean body mass. Since your bones and organs are an unusual source of weight change, lean body mass really means muscle. If you diet to lose weight rapidly, there is a good chance that you will lose muscle at the same time. Should the weight later return, there is also a very good chance that what comes back will be fat. While net weight may be the same at the end of some time period, cycling weight change may shift body composition from muscle to fat. If you have vascular disease and lose muscle or gain body fat your chance of having complications of your disease is increased.(4, 5) Researchers examining diets and weight loss have used body composition or more importantly change in body fat to describe the impact of diets and exercise regimens for many years. The easiest method to measure a change in body fat is to use the skin folds around the belly, on the arms, back and elsewhere. For you and I, the easiest measure is the waistline. If it's shrinking, slowly and on purpose, any change in diet and activity is probably helping, even if weight hasn't changed greatly. An effort to lose body fat should be a permanent change of habit. Diet and exercise designed to keep muscle mass and lose fat is almost certainly beneficial. The lesson suggested by the new observations is that attempts to change body composition and weight secondarily should have goals set over six months to years with interventions that are long lasting, if not permanent. Does the type of diet or exercise influence the type of weight that is lost? In addition to seeking some evidence to show why changing weight and increased risk go together, my questions are, 1. What diet/exercise combination best sustains muscle while reducing fat? a. Generally b. In specific groups with physical limitations 2. Is there a rate of intentional, guided weight loss, targeting fat, at which muscle is sacrificed? Stated differently, if you're trying to lose fat and are losing weight, can the speed that it is coming off warn you that you may be losing muscle too? The worst possible conclusion to draw from this study is that a change in lifestyle geared to losing weight is bad. The goal remains laudable when the approach is a long-term change with a goal of reducing body fat but maintaining muscle.
Keywords: Obesity, Diet, Heart Attack, Weight loss
1. Bangalore S, Fayyad R, Laskey R, DeMicco DA, Messerli FH, Waters DD. Body-Weight Fluctuations and Outcomes in Coronary Disease. New England Journal of Medicine. 2017;376(14):1332-40.
2. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss. Circulation. 2006;113(6):898.
3. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. The Lancet. 2006;368(9536):666-78.
4. Allison DB, Zannolli R, Faith MS, Heo M, Pietrobelli A, VanItallie TB, et al. Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies. Int J Obes Relat Metab Disord. 1999;23(6):603-11.
5. Santanasto AJ, Goodpaster BH, Kritchevsky SB, Miljkovic I, Satterfield S, Schwartz AV, et al. Body Composition Remodeling and Mortality: The Health Aging and Body Composition Study. The Journals of Gerontology: Series A. 2017;72(4):513-9.
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