Deconditioning and the Flabby Heart

 

You know the feeling. Every weekend warrior knows the feeling. You spend time building up your exercise capacity by biking, running, swimming, hiking, or going to the gym. Then for some reason (illness, injury, other obligations) you have to stop exercising for weeks or months. When you return to your activity, you are more short of breath, you don’t have the same exercise capacity, and you feel “out of shape”. What happens to the heart during deconditioning (the medical term for “out of shape”)?  Does deconditioning occur with elite athletes or astronauts? Does it happen on weekdays to weekend warriors?

 

The heart is a muscle. With training athletes can build up their arm and leg muscles.  The same process builds up the heart muscle as well. The cardiac effects of long-term exercise include increases in the size of the heart, the thickness of the heart’s muscle and the cardiac mass.  (The heart enlarges to accommodate the increased blood flow during exercise. The walls of the main pumping chamber, the left ventricle, thicken and become more muscular to pump the excess blood.  Cardiac mass is the weight of the heart and represents the long-term effective of blood pressure on the heart). A larger, thick walled heart is called an athlete’s heart. Unfortunately, a thick muscular athlete’s heart resembles a form of cardiac pathology, hypertrophic cardiomyopathy (a congenital abnormality where the heart muscle is very thick and there is a risk for arrhythmia).  Congenital hypertrophic cardiomyopathy is the most common reason for sudden cardiac arrest in the athlete. Athletes are screened to see if they have hypertrophic cardiomyopathy and, if present, vigorous exercise is prohibited. Unfortunately, it is difficult to differentiate between pathologic hypertrophic cardiomyopathy and an athlete’s heart. One way to tell the difference is to have the athlete stop exercising for a period of time, a method called detraining. If the heart muscle reverts to normal thickness during detraining, then it is an athlete’s heart.  Studies on Olympic athletes have shown that after about 12 weeks of detraining left ventricular thickness rapidly decreases (thickness goes down by 15-33%).  In addition, cardiac mass decreases quickly as well, within 4 to 8 weeks. For full regression of left ventricular thickening, detraining should last 6 months.

 

The healthy heart needs exercise, but it also needs gravity. Both of those items are in short supply to astronauts on a long-term space mission. The lack of gravity has the same effect as prolonged bed rest on the heart, worsening the deconditioning that takes place in space.  Studies performed on astronauts who spend months in space show that space flight causes significant cardiac atrophy. After only a few weeks in space, there is a reduction in the heart’s muscle mass. It is estimated that cardiac muscle mass decreases about 1% per week in flight. This deconditioning has obvious consequences for prolonged space missions. A recent study followed astronauts on the International Space Station. The astronauts were in flight for many months and spent 2 hours each day doing endurance and resistance training. Cardiac work load was 12% lower in space than on Earth due to zero gravity and the confines of the station. Despite the lower work load, the astronauts’ heart muscle mass stayed intact. It seems that exercise can preserve the heart’s structure and function offsetting space flight deconditioning. 

 

Most people don’t have to worry about their heart becoming too thick from exercise or losing cardiac muscle mass on a space flight. However, deconditioning occurs in the average person, with changes similar to the detrained athlete or the astronaut in space. Deconditioning is defined as the adaptation of the body to a less strenuous environment and the decreased ability to function with physical exertion. The body resets to a lower level of functioning so that when it is asked to increase physical activity, it is unable to meet the demand. Deconditioning occurs when people stop exercising; the most extreme example is bed rest.  Many studies of patients during bed rest show that skeletal muscle strength is lost rapidly (10-20% in a week, 50% in 3 to 5 weeks). Skeletal muscle mass also decreases 3% within a week of bed rest. In addition, bone density decreases as well. From the cardiovascular standpoint, blood volume goes down and heart rate goes up with bed rest. This means that the body cannot compensate when going from a supine to a standing position; blood pressure drops on standing and patients can pass out. Lastly, bed rest causes cardiac atrophy. With 2 weeks of bed rest, there is a reduction in cardiac muscle mass of 5%, similar to what happens with astronauts in space and the detrained athlete.

 

Can the “weekend warrior”, someone who only exercises one or two days per week, become deconditioned during the work week? Likely this is not the case as loss of cardiac structure and function occurs after weeks to months of inactivity. In fact, a recent study showed that as long as weekend warriors exercised for 150 minutes per week or more, they had similar reductions in their risk for heart attack, stroke, atrial fibrillation and heart failure as people who exercise daily. 

 

You worked hard to build up your exercise capacity. Don’t stop now and let your heart become flabby and deconditioned. Keep active and keep exercising a minimum of 150 minutes per week, even if it is only two days a week.

 

 

 

The Café Coffee Culture and Cardiac Disease

 

Imagine yourself walking down a street in a French town. You spot a picturesque café in the square, perhaps one that had been painted by Van Gogh. People are in the café, relaxed, sipping their coffees. It looks so inviting. You want to join them and order a nice café Americano, but you wonder how good is coffee for the heart? 

 

Before we drip into the medical data, some fun facts about coffee. Coffee grows on a bush and the beans are actually the pit of a berry, which makes coffee a fruit. Coffee has been consumed for about 500 years. In the US, about 85% of adults drink coffee daily, averaging 1.5 standard cups per day. Brazil is the largest exporter of coffee in the world and Finland is the worldwide leader in coffee consumption.Now let’s pour over the physiological effects of coffee. Coffee is not just caffeine; the beans have over 100 active substances which have a variety of metabolic effects. Drinking coffee causes the heart rate and blood pressure to increase. Effective sleep may be suppressed. Caffeine increases catecholamines (adrenaline). Coffee stimulates the electrical system of the heart. For these reasons, many cardiologists recommend decreasing or stopping caffeine use. Is that recommendation justified?

 

Does coffee cause heart arrhythmias?

Doctors have always felt that coffee may increase the number of premature atrial contractions (PACS) and premature ventricular contractions (PVCs).  Increased PACS may result in atrial fibrillation (Afib) while increased PVCS may cause ventricular arrhythmias. A recent study in healthy volunteers showed that coffee did not increase the number of daily PACs, but may increase PVCs. The accumulated medical literature has shown that coffee drinkers have a lower risk for Afib than those who do not drink coffee. Drinking one cup per day lowers the risk for Afib by 20%. The reason for this may be that long-term coffee drinkers develop a tolerance to the electrical stimulating effects of caffeine. However, there is a lot of individual variation in terms of response to coffee. Approximately 25% of patients report coffee as a trigger for Afib. Clearly those patients should avoid it. Similarly, the literature does not show an increase in ventricular arrhythmias with coffee consumption, despite a possible increase in PVCs. This holds true even for patients with history of significant ventricular arrhythmias. It appears that drinking coffee is safe for most patients in terms of their potential for arrhythmia.

 

Is it the caffeine?

Coffee is the most commonly used stimulant in the world. Coffee activates the central nervous system, boosts alertness and has a variety of psychoactive effects. Are these effects due solely to caffeine? In an interesting study people were given coffee or plain caffeine in water and then underwent MRI scans of the brain. The coffee drinkers had a heightened state of preparedness, were more responsive and had higher executive brain functioning than the plain caffeine group. It appears there is more to coffee than just caffeine. 

 

Does coffee raise blood pressure?

The effect of coffee on blood pressure is still not decided. Drinking a cup of coffee will transiently increase blood pressure for about 30 minutes.  Coffee stimulates catecholamines and stimulates receptors in the blood vessels to constrict, causing an increase in blood pressure. However, this is counterbalanced by an increase in nitric oxide, which dilates blood vessels. Over time, the acute effect of a blood pressure bump with each cup is blunted in regular coffee drinkers. In fact, regular consumption of coffee is associated with lower overall blood pressure readings compared to nondrinkers. It appears that coffee doesn’t cause hypertension.

 

What are the other metabolic effects of coffee?

Coffee has both good and bad effects. Regular coffee drinking lowers body fat and reduces the risk for obesity.  In addition, coffee lowers the risk for type 2 diabetes. On the other hand, coffee may increase cholesterol levels. The effect depends on the type of coffee, the degree of roasting and the type of brewing. Boiled, unfiltered coffee (such as Turkish or Greek coffee, made by boiling water with coffee grounds in a pot) raises cholesterol more than filtered coffee. Other nonfiltered coffees, such as espresso, are significantly associated with raised serum cholesterol levels. Filtered coffee can raise cholesterol but not as significantly as unfiltered coffee. There is no increase in cholesterol with instant coffee. It appears that drinking filtered coffee is the safer than alternatives. 

 

Does coffee reduce the risk for cardiac events?

In the literature, coffee drinkers have consistently had a lower risk for heart problems and death. A study from Europe in 2017 showed that drinking 2 to 4 cups of coffee per day reduced the risk of dying by 15%, reduced the risk of cardiac death by 17% and reduced the risk of dying from cancer by 4%. A more recent study confirms and expands these findings. The study followed 500,000 people for 10 years. In people without known heart disease, drinking 2 to 3 cups of coffee per day lowered the risk for heart artery disease, heart failure, stroke and dying from any cause. People withheart disease also showed improved survival and no increased risk for arrhythmias. The relationship held regardless of instant versus ground coffee, or decaf versus caffeinated coffee. The reason for these favorable benefits may be coffee’s metabolic effects (lower risk for obesity and diabetes), as well as coffee’s anti-inflammatory and anti-oxidant properties. In addition, coffee drinkers consistently do more physical activity than nondrinkers.  It seems that 2 to 3 cups of coffee per day is the sweet spot, a level of consumption where coffee is not only safe, it may be cardioprotective.

 

It can be concluded that coffee is not associated with high blood pressure, significantly elevated blood cholesterol (if the coffee is filtered) or dangerous arrhythmia. It is associated with a lower risk for obesity, type 2 diabetes, heart artery disease, stroke and death.  So find yourself a nice little café. Order one or two cups of (filtered) coffee. Then sit and watch the world go by, guilt free.

 

 

 

Personality Traits And Cardiovascular Disease

 

One of the classic scenarios in psychological evaluations is to show a person a glass that is 50% filled with water.  Is the glass half full or half empty?  How the person answers that question can determine a lot about their psychological state and may show their risk for future heart disease. 

 

For years the face of heart disease was a man who was highly ambitious, competitive, aggressive, impatient, goal- directed and willing to take risks. The type A personality was originally described in the 1950's by two cardiologists. They went on to show that the type A person had higher levels of cholesterol and a higher risk for heart disease. In addition, they found that the opposite of the type A, a relaxed, easy going, laid-back person, a type B personality, had a lower risk for heart disease. These stereotypes have persisted to this day.  More recent data found no significant link between type A personality and heart disease. However, two components of the type A personality, anger and hostility, are strongly associated with cardiac disease.  Studies have shown that anger and hostility significantly increase the risk for cardiac events in healthy people as well as those with established heart disease.  Anger causes excess catecholamine (adrenaline) release, an increase in heart rate and elevated blood pressure which can lead to angina and a heart attack. An outburst of anger is a well-established trigger for an acute heart attack. Chronic anger and hostility lead to the initiation and progression of blockages in the heart arteries, especially in young men. A new personality type was identified in 2000 and named type D (or “distressed”) personality. The type D personality has two components. The person exhibits negative emotions (anxiety, worry, neurotic) and social inhibition (can’t express emotions, thoughts or behaviors in a social situation). It is often associated with anger, hostility and social isolation as well. The type D personality is associated with cardiac disease including angina, heart attack and an increased risk for cardiac death

 

Neuroticism is another personality trait tied to adverse cardiac disease. Neurotic individuals have emotional instability, difficulty handing stressful situations and “fly off the handle” when under pressure. On the other hand, those with low neuroticism scores are more emotionally stable, calmer, even-tempered and less reactive to stress. Individuals with high neuroticism scores have more anxiety, moodiness, fear, anger, frustration, pessimism, and loneliness than those with lower scores.  They often turn to maladaptive behaviors (substance abuse, alcohol). In addition, people with high neuroticism scores were more likely to develop atrial fibrillation and to be diagnosed at an earlier age then those with lower scores. 

 

On the other hand, certain personality traits are cardioprotective. These include optimism, conscientiousness, openness to new experiences and curiosity.  Optimism is defined as the expectation of good things in the future (while its opposite, pessimism, is expecting something bad to happen down the road).  Individuals with high optimism scores have lower risk for angina, heart attack, stroke, cardiac death and all cause death. Why is this? Optimists and people with psychological well-being have favorable physiologic parameters including lower blood pressure, better cholesterol levels and less sympathetic activation (lower adrenaline levels).  They smoke less, exercise more, eat better and have less tendency for obesity. In addition, optimists are more likely to seek help in difficult social situations. They have larger and stronger social networks for support. They act on medical advice more readily. Lastly, optimists can weather the harmful effects of stress due to their inner and outer support systems. Meanwhile, pessimism has been shown to increase the risk for cardiovascular mortality.

 

So, when confronted with the question about that glass of water, don’t get angry. Don’t become hostile. Don’t get depressed if you can’t come up with an answer. Look for the positives, try to maintain an optimistic viewpoint and say that it is half full. Your heart will thank you.

 

When Anthropology Meets Cardiology

 

When Mount Vesuvius, a volcano near Naples Italy, erupted in 79 AD, it caught the townspeople of nearby Pompeii and Herculaneum by surprise. Many were able to escape, but many died instantly, buried by lava and volcanic ash. Due to the nature of their death, their bodies were well preserved. Recently, scientists were able to study the bodies of these early Mediterranean people and were able to determine what they ate. How does the ancient Mediterranean diet compare to the modern version?  How can the study of ancient peoples give us insight regarding heart healthy diets in today’s world?

 

The Mediterranean basin has been called the cradle of civilization. It stretches from the Nile to Rome and has housed advanced civilizations for thousands of years, including the Egyptian, Assyrian, Babylonian, Persian, Phoenician, Greek and Roman. The Mediterranean diet is linked to the fertile land of the region.  It is more than a diet; it is a way of life and based on traditions linking the land to the preparation, cooking and enjoyment of the food. The key elements of the Mediterranean diet include oil (especially olive oil), whole grains, wine, vegetables, sheep and goat cheese, seafood and very little meat. Whole grains include bread, cereals, couscous, pasta, rice, corn, oats and barley.  The description of the ancient Mediterranean diet comes mainly from written accounts. For example, texts describe the diet of the ancient Greek Olympic athletes starting around 700 BC. The diet was mostly vegetarian, consisting of barley porridge, cheese, fresh vegetables, lentils, beans, seafood, eggs and fresh fruit, mainly figs. Sweets were frowned upon. Initially meat was not a part of the athlete’s diet, but as time went on, meat was incorporated more and more.  Fast forwarding to Pompeii and the modern day, we now have concrete proof of what Roman era Mediterranean people actually ate. Scientists have been able to test the bones of the people frozen in time by the eruption of Mt Vesuvius. Using bioarcheological approaches they determined that the people of Pompeii ate a lot of fish, more than is consumed with the modern Mediterranean diet.  In addition, locally grown fruits and vegetables were eaten. The majority of their food energy came from seafood and cereals, although grain consumption was less than today’s diet. After the fall of Rome, the Mediterranean diet faded during the Middle Ages. It rose again from the ashes and poverty following World War II when meat was scarce and people turned once again to what could be grown locally. The cardiac benefits of the Mediterranean diet were first described in the 1950’s by Ancel Keys, a University of Minnesota researcher who discovered that people in poor towns in southern Italy were healthier than wealthy people in New York City. He conducted the Seven Countries Study and showed that the Mediterranean diet resulted in low levels of cholesterol in the blood as well as low levels of heart artery blockages. 

 

Anthropological data has shown that pre-agricultural hunter-gatherer populations derived a majority of their energy from animal based foods such as meat, fish, birds and eggs. The keto and paleo diets were developed to mimic these eating patterns.  These diets are very low in carbohydrates and high in saturated fat. It is generally believed that hunter-gatherers had low levels of heart disease. Is this true? A recent study performed CT scans on mummies from four regions, including ancient Egypt, Peru, southwest US, the Aleutian Islands and going back 4000 years. Atherosclerosis (calcified plaque in the wall of an artery) was found in 34% of the mummies and was found in all four regions.  In addition, atherosclerosis was present in 60% of the hunter-gatherers.  Atherosclerosis is felt to be a modern disease, but it is clearly present in our ancient ancestors, including hunter-gatherers. 

 

Since atherosclerosis seems to be a fact of human existence, which diets help protect the most against atherosclerotic heart artery disease? In 2021 the American Heart Association outlined its requirements for a heart healthy diet and ranked popular diets on how well they met the criteria. The recommendations included consuming:

Fruits and vegetables

Whole grains (rather than refined grains)

Plant based proteins (such as legumes and nuts)

Fish and seafood

Low-fat or fat-free dairy products

Lean meat or poultry

Plant oils (such as olive oil) 

Minimally processed foods

Minimal added sugar 

Little or no salt

Low amounts of alcohol

The dietary patterns that aligned the most with these criteria included Mediterranean, DASH (Dietary Approaches to Stop Hypertension), pescetarian vegetarian (excludes meat and poultry, includes fish), vegan and low fat. At the bottom of the list were the keto and paleo diets. Is there data, some meat, to back these rankings? One study reviewed all of the literature on seven diets. It found that the Mediterranean diet lowered all deaths, cardiac deaths, stroke and heart attacks. The low fat diet lowered all cause deaths and heart attacks. All of the other diets, including the very low fat Ornish and Pritikin diets, had little or no benefit. Studies on low carbohydrate, high fat “keto-like” diets have not been good. One study had 1220 people and followed them for 12 years. The keto-like diet patients had high levels of LDL cholesterol and were twice as likely to suffer from cardiac events.  Another study of 370,000 people, followed for 23 years, found a higher mortality rate for those on a low carbohydrate diet compared to a low saturated fat diet. 

 

Clearly no randomized controlled trials were done in ancient times to see if any of the diets conferred benefit from heart disease. This was due to a lack of scientific knowledge as well as the fact that our ancestors succumbed at early ages due to infectious disease, famine, the tip of the sword from an enemy or volcanic ash, well before heart disease became manifest.  What is clear from the study of mummies is that high fat diets, keto or paleo, did not protect against atherosclerosis. In addition, our modern studies show that these diets are detrimental to heart health. Heart patients should avoid these types of diets.  On the other hand, the Mediterranean diet is a sustainable, lifelong eating plan that continues to sit atop Agamemnon’s throne as the king of the heart healthy diets. The Mediterranean diet, along with DASH, vegetarian, vegan and low fat diets should continue as staples for the heart patient. 

 

 

Can Congestive Heart Failure Be Cured By Walking With Friends?

Congestive heart failure (CHF) is the inability of the heart to pump blood to meet the requirements of the body. CHF is classified into two groups based on ejection fraction. Ejection fraction (EF) is the percentage of blood ejected by the heart with each heartbeat. Normal EF is greater than 55%. CHF with reduced EF includes patients with EF less than 40% while patients with CHF with preserved EF have EF greater than 50%. CHF is an enormous global problem affecting more than 60 million people worldwide. CHF is the number one reason for hospitalization in the US and associated with frequent hospitalization, high healthcare use and cost. Symptoms of CHF include shortness of breath, trouble breathing with exertion or laying flat in bed, severe exercise intolerance, easy fatigability, and swelling. In 2021, a universal definition of CHF stated that CHF is a clinical syndrome with symptoms caused by a structural heart problem plus either an elevation in the blood of natriuretic peptides or objective evidence of congestion (by physical examination or chest X-ray). Natriuretic peptides are released when the heart is stretched or stressed, as in CHF. There are two natriuretic peptides; BNP and pro-BNP. CHF is present when BNP is greater than 35pg/ml or pro-BNP is greater than 125 pg/ml.

 

CHF with preserved EF affects half of all CHF patients. It affects women more than men and it is increasing in prevalence compared to CHF with reduced EF.  CHF with preserved EF is associated with and may be caused by hypertension, obesity, diabetes, heart artery disease, sleep apnea, kidney dysfunction and advanced age. Treating CHF preserved EF is difficult and frequent hospitalizations often result. A recent guideline recommends SGLT2 inhibitors as first line therapy. These medications, Jardiance and Farxiga, relieve congestion and promote weight loss. In addition, diuretics such as furosemide (Lasix) and spironolactone help in the treatment of fluid overload. The next line of recommended medications include Entresto, valsartan or losartan. Beyond medication, what else can be done? Recent information postulates that CHF preserved EF is an exercise deficiency and a social isolation problem. Addressing those issues could go a long way to treating the disease.

 

CHF preserved EF is a syndrome of exercise deficiency.

An intriguing article hypothesizes a spectrum of shortness of breath with exertion. At one end is the patient with CHF preserved EF. With exercise, such as climbing the stairs, there is insufficient cardiac output to meet the demands of the muscles, pressure goes up in the heart, and breathlessness ensues. The same series of events happens with an elite athlete. The difference is the workload; the CHF patient just walks up the stairs, the athlete has run 26 miles. The athlete has larger cardiac chambers, more heart muscle mass and a compliant heart that can handle high volumes and work loads. The patient with CHF preserved EF has a small, stiff, less compliant heart that cannot handle increased volumes with exertion.  Normal aging results in a smaller heart size, higher filling pressures during exertion and a greater potential for CHF. Being sedentary over the course of a lifetime exacerbates the effects of aging.  For adults who sit many hours each day the cumulative effects of a sedentary lifestyle plus the effects of aging plus other factors (for example, high blood pressure, smoking, diabetes) combine to cause CHF preserved EF. On the other hand, adults who have spent a lifetime exercising regularly can stave off the cardiac stiffness that occurs with age and can avoid CHF. Fortunately, for patients with CHF preserved EF the adverse cardiac effects can be reversed with physical training. For this reason, the American Heart Association recommends structured exercise for patients with CHF preserved EF. Structured exercise, or cardiac rehab, has been shown to reduce hospitalizations and reduce cardiac events. Not all those with CHF preserved EF fall into the category of exercise deficiency; it is reserved for the subset of patients with habitually low levels of physical exertion.

 

CHF preserved EF is a syndrome of social isolation and loneliness.

Social factors are a well-known contributor to heart disease. A recent study followed more than 400,000 people for more than 12 years to see if social isolation or loneliness were associated with CHF. Social isolation was defined as objectively being alone or having few social connections. Loneliness was defined as a painful feeling resulting from a desire for more social connections. Those with social isolation or loneliness were more likely to be men and to have unhealthy lifestyles (smoking, diabetes, obesity, physical inactivity). The study found that both social isolation and loneliness increased the risk for CHF by 15-20%. 

 

So, if you have CHF, or are at risk for CHF, grab a friend, talk a walk, eat, sleep, repeat.

 

The Taxing Pain Of Statin Intolerance

 

There are certain things in life that are inevitable; death, taxes and, for the physician, patient intolerance of their medication. Statins are wonderful drugs which have revolutionized medicine and almost single handedly reduced the global burden of heart disease.  Statins lower “bad cholesterol” (LDL, low density lipoprotein) and raise the “good cholesterol” (HDL, high density lipoprotein). In addition, statins have anti-inflammatory effects that contribute to their ability to lower heart disease. Unfortunately, statins have side effects including raising liver enzymes and causing muscle pains. Many patients cannot tolerate statins due to muscle symptoms.. What is statin intolerance? What new medications are available for patients with statin intolerance?

 

There are many medications available to treat high cholesterol. However, to be deemed beneficial a medication must meet two requirements. Number one, it must lower LDL substantially. Number two, it must reduce major adverse cardiac outcomes (heart attack, stroke, cardiac death).  Medications such as welchol, niacin, fenofibrate, fish oil (omega 3 fatty acids) lower LDL cholesterol, but do not reduce cardiac risk and are therefore not part of the modern cardiac armamentarium. Statins fulfill the criteria by lowering cholesterol and reducing cardiac events. For every 2 mg/dl reduction in LDL, there is a 1% reduction in cardiac outcomes. For example lowering LDL from 140 mg/dl to 100 mg/dl (a reduction of 40 mg/dl) not only reduces cardiac events by 20%, but also lowers mortality by 10%. The most common reason patients cite for stopping their statin is muscle pain. Muscle symptoms include soreness, aching, weakness or cramping and affect large muscle groups (such as the thigh). Muscle pain causing statin intolerance has been reported between 5% and 50% of patients. A recent large study (including 4 million patients) determined that true statin intolerance occurred in about 9% of patients taking a statin. Statin intolerance has been defined by the FDA as " the inability to tolerate at least two statins at the lowest approved doses due to muscle symptoms". Risk factors for statin intolerance include female sex, obesity, underactive thyroid, diabetes, alcohol use, chronic liver or kidney disease, use of calcium channel blocker, and the use of high doses of statin. Factors not associated include smoking and high blood pressure. Statin induced muscle pain usually occurs early in treatment (the first few weeks up to two months). However, the enormous benefit of statins is such that treatment should not be abandoned if a patient reacts to a single agent. Other statins should be tried and dosing altered to try to keep them on the medication. If a patient is truly statin intolerant after several tries, then there are new, nonstatin alternatives.

 

The first alternative medication for the statin intolerant patient is ezetimbe (Zetia). Ezetimbe alone reduces LDL by 18% and in combination with simvastatin 25%. The combination medication lowers the risk for cardiac events by 8%. Ezetimbe is rarely used by itself, rather it is used to lower the statin dose while still providing cardiac protection. The next class of agents are the PCSK9 inhibitors alirocumab (Praluent) and evolucumab (Repatha) which were approved for use by the FDA in 2015. These medications are given by a self-administered injection under the skin (much like an insulin shot) every two weeks. They lower the LDL by a whopping 58% (Praluent) and 64% (Repatha) and lower cardiac event rates by 15%.  The next agent is inclisiran (Leqvio) which was approved for use by the FDA in December 2021. It too is an injectable medication but this is given every six months. Inclisiran has been tested in patients with familial hypercholesterolemia who still have high levels of LDL despite taking a statin. In these patients, inclisiran lowers LDL by 50% on top of statin treatment. Trials are ongoing evaluating inclisiran’s ability to lower cardiac events.  In addition, it has not been tested in statin intolerant patients. However, it may prove very useful in this population. Side effects include only injection site reactions and no muscle pain. The last medication is bempedoic acid (Nexletol) which the FDA approved in February 2020. Bempedoic acid has been tested in patients with statin intolerance. Alone it lowers LDL by 21% and in combination with ezetimbe LDL is lowered 38%. Importantly, bempedoic acid was recently shown to lower the cardiac event rate by 13%. In addition, it seems to have anti-inflammatory properties (like statins) whereas ezetimbe and PCSK9 inhibitors do not. Side effects include gout and gallstones but no muscle symptoms. All of these characteristics make it a good alternative for statin intolerant patients.

 

Despite a plethora of good alternatives, the principal is to have patients take a statin. Fortunately, there are other medications if they cannot continue on statins. In terms of life’s inevitabilities, physicians can’t reduce the tax burden. However, there are now viable options for patients with statin intolerance that also reduce the risk for cardiac death. Two out of three ain’t bad.

 

 

AED Density

 

Sudden cardiac arrest is an abnormal heart rhythm most often caused by ventricular fibrillation (an irregular heart rhythm from the lower chambers of the heart).  When the heart’s ventricles are fibrillating, they cannot pump blood to the brain and vital organs. If not treated promptly, this leads to death.  Sudden cardiac arrest is common and affects 350,00 people in the US each year. Surviving sudden cardiac arrest requires prompt cardiopulmonary resuscitation (CPR) and defibrillation with an Automatic External Defibrillator (AED).  Timing is everything; if an AED shock is provided within one to two minutes of going into sudden cardiac arrest about 50% of victims will live. However after 10 minutes, less than 10% will survive. We have all seen this in real time recently. Due to the quick response and the coordinated efforts of a team who practiced for just this type of situation, Damar Hamlin is alive today.  However, most sudden cardiac arrests do not happen in a controlled environment such as a cardiac care unit. The big question then is how to get responders and AEDs to sudden cardiac arrest victims as fast as possible.

 

If a patient has cardiac arrest in the hospital, doctors and nurses with advanced cardiac training can often successfully resuscitate the patient. If someone suffers sudden cardiac arrest outside of the hospital, it is a different story. In studies it has been shown that 8% of cardiac arrests occur in a public setting and witnessed by bystanders, but the vast majority of out of hospital cardiac arrests occur in the home (75%).  The overall survival rate for out of hospital cardiac arrest is only between 2% and 14%. One of the biggest barriers to successfully resuscitating a patient out of the hospital is getting trained responders to the victim. Once a cardiac arrest has been called to 911 or emergency services, a dispatch is placed to first responders; police, fire and ambulance corps. However, if it takes emergency responders more than ten minutes to locate and get to the victim, the outcome is usually not good. If bystanders near a victim are able to start CPR and, even better, use an AED, the chance of survival increases dramatically. Resuscitation by bystanders is associated with survival rates between 53% and 66%. For comparison, survival rates for emergency medical personnel is between 28% and 43%.  Most studies show a 2 fold better chance of living if the patient is treated immediately by a bystander. There are a number of volunteer responder programs around the world, including Denmark, Netherlands, United Kingdom, Australia, US and Canada. The idea is to alert volunteer trained responders about a cardiac arrest and direct them to the victim so that prompt CPR can be initiated.  The programs work in the following way. Once a cardiac arrest has been called in to a central dispatching agency, registered volunteers in the vicinity of the arrest are contacted via text message. Some responders are directed to the nearest available AED, while others are sent straight to the patient to start CPR. The system keeps notifying volunteers until a critical mass have responded and are on their way. How many responders are needed to optimally manage a sudden cardiac arrest?  When 3 or morevolunteersresponded before emergency medical services, there was a greater chance for bystander defibrillation with an AED.

 

The other huge barrier to successful resuscitation is getting an AED to the victim as soon as possible.  AEDs have become ubiquitous. About 500,000 to 1 million were sold in the US last year and there are about 3.2 million AEDs in public settings. Yet, there is still a shortage. AEDs in public places (for example gyms, casinos, airports, arenas, shopping malls) should be prominently mounted with easy to see signs. In addition, emergency services and security personnel should know the exact locations of AEDs. What is the optimal density of AEDs?  In a large public space how close together should AEDs be placed? In 1999 AEDs were installed in O’Hare airport in Chicago. AEDs were placed a “brisk 60-to-90 second walk apart”. The survival rate for cardiac arrest at the airport is 56%. The American Heart Association recommends an AED within a 3-to-5 minute round trip walk from anywhere in a public place. This translates to each AED covering about 100 yards in each direction. 

 

In case of sudden cardiac arrest in the home, getting an AED to the person is very problematic. As described above, formal programs will send out texts to responders and direct them to the location of a known AED.  What is the optimal density of AEDs in residential areas? One study from the Netherlands found that approximately 2 AEDs per square kilometer (5 AEDs per square mile) in residential areas was optimal coverage. However, in Holland there is a national registry for all public and private AEDs, including location. When emergency services are called, responders are directed to the nearest AED. Another study from Copenhagen concluded that the optimal coverage was 16 AEDs per square kilometer (41 AEDs per square mile) in residential areas. Keeping in mind that the Netherlands and Denmark are each about 16,000 square miles, that is not an insurmountable number of AEDs to provide residential coverage. The United States is 3,531,905 square miles.Novel ideas that are being piloted include delivering an AED via a drone to the victim and having ultraportable AEDs carried by volunteer responders.

 

You may ask, “How does this information help me? I can’t afford to outfit the US with millions of AEDs.” This is a valid question, but there are still lessons for the general public.  The first is to get trained in CPR. The local hospitals have CPR classes for the community. You never know when you might need these skills. Next, even if you lack formal training, this should not deter you from attempting to save a life. AEDs are easy to use and they help guide the responder through the process of deploying them. Next, if you see a resuscitation in progress, go and help. Remember, the more hands, the greater the chance to save a life. Lastly, advocate in your community for greater AED density.