Thumbs Up For Aortic Screening

 

 

The thumb is a remarkable appendage.  By allowing us to grasp objects, to use tools, to write, the thumb has helped us evolve above and beyond all other animal species. Can the thumb also be useful in helping us detect an enlarged aorta? 

 

The aorta is the main artery of the body. It arises from the heart, courses through the chest and abdomen and ends by splitting into two arteries to supply blood to the lower extremities. Arteries arise from the aorta to supply blood and oxygen to the heart, brain, stomach, kidneys and all of the muscles of the torso and the upper extremities. The aorta is divided into two main parts, the thoracic (chest) aorta and the abdominal aorta. One of the most serious, and deadly, problems with the aorta is an aortic aneurysm.  An aneurysm is an enlargement of the aorta. As the aortic diameter increases and balloons out, the wall of the aorta weakens.  At some critical size, the wall is so weak that it can burst open. Unfortunately when that happens, the patient most likely will die from bleeding. The keys to managing an aortic aneurysm is to identify an aneurysm, monitor its growth and size and refer the patient to surgery to repair the aorta before it ruptures.  Aneurysms of the thoracic and abdominal aorta have different causes and different ways to monitor them. 

 

The exact cause of abdominal aortic aneurysm (AAA) is not known. It does occur in families and those with a first-degree relative with AAA are at two times the risk. AAA can occur in the setting of atherosclerosis. Risk factors for AAA include male sex, older age, smoking, and hypertension. Aneurysms that are greater than 5.0 cm in diameter are at increased risk for rupture and at that level of dilatation patients are referred to surgery for repair. AAA can be detected by physical examination. A pulsatile mass is felt in the area around the umbilicus. Ultrasound is very good for detection and screening of AAA. It is recommended that men over age 65 who have ever smoked or who have a family history of AAA have a one-time screening (the benefits of screening women hasn’t been determined). Once identified, yearly ultrasounds are used to follow patients with AAA. If there is rapid growth, or the AAA reaches 5.0 cm, then a CT scan is done to further delineate the anatomy and help in planning for surgery.

 

There are many different causes for thoracic aortic aneurysm (TAA). Connective tissue diseases are an important etiology. In these conditions, patients are born with loose muscles and joints. They can perform all kinds of contortions (they are “double jointed”).  The aorta has muscle and connective tissue within its walls; this makes it elastic, allowing it to expand when the heart pumps blood through it and to  relax when there isn’t blood flow. These elastic properties help the aortic wall handle the high pressure of blood flow, without rupturing. Unfortunately the same connective tissue laxness in these patients also causes weakness within the aortic wall. This leads to TAA and these patients are prone to rupture at smaller aortic diameters than other TAA patients.  The most well known connective tissue disease is Marfan’s Syndrome. These patients are tall, skinny and lanky (Abe Lincoln was thought to have it). They may have TAA, their aneurysms can grow rapidly and are at risk for bursting at about 4.5 to 5.0 cm.  Athletes with Marfan’s Syndrome are barred from playing sports because extreme physical activity can increase the risk for their aneurysm bursting. Therefore it is very important to identify and follow these patients. Other causes of TAA are bicuspid aortic valve (the aortic valve has two leaflets instead of the normal three leaflets), atherosclerosis, vasculitis (inflammation of the wall of the aorta), infection (for example, syphilis) and trauma.  Detection and screening for TAA is more difficult than with AAA. The echocardiogram (ultrasound of the heart) can image parts of the thoracic aorta. It is not an ideal screening tool as it can’t view the entire thoracic aorta and measurement of aortic size is fraught with error.  However, it is noninvasive and doesn’t require intravenous contrast.  The gold standard for measuring TAA is either CT scan or MRI, both of which require intravenous contrast. Due to the contrast, the cost and the radiation exposure (for CT scan) these tests are not ideal for screening.  A good, low cost, low risk screening test for TAA is sorely needed. Enter the thumb test. The thumb test is simple. Hold up one hand and keep the palm flat. Stretch the thumb as far as possible across the palm. If the thumb crosses beyond the edge of the palm, the test is positive.  A positive thumb test indicates that the joints are loose, due to a connective tissue disease and that a TAA may be present. The majority of aneurysm patients do not have a positive thumb test, but if the test is positive there is a very high likelihood of having a TAA. A negative test does not exclude the possibility of an aneurysm.

 

If you are a male, over 65 years old and have ever smoked or have a family history of AAA or if you have a positive thumb sign, talk to your doctor about screening for an aneurysm. It may save your life.

Humor Explains (And Cures) Everything

Plato and a platypus walk into a bar... This isn’t the start of some highbrow joke, but the title of a book by Harvard trained philosophers Thomas Cathcart and Daniel Klein. In the book the authors plausibly spell out how jokes and humor can explain all of philosophy. Jokes and philosophical concepts are similar in that they both make you think; both flip the world upside down and uncover hidden truths about life. Joking about the three main branches of philosophy, ethics, logic and metaphysics, helps us understand these lofty ideas.  Metaphysics tackles the Big Questions, for example: What is reality? What is the meaning of life? If humor can help us understand metaphysics, humor can therefore explain everything! If humor is this powerful, we need to define it.  The humor writer and philosopher Dave Barry defined humor as, “a measurement of the extent to which we realize that we are trapped in a world almost totally devoid of reason. Laughter is how we express the anxiety we feel at this knowledge“. Speaking of anxiety, Sigmund Freud wrote a book analyzing jokes and their relationship to our dreams, our inhibitions and our unconscious thoughts. So a good joke not only provides a hearty laugh, but can have deep philosophical and psychological meaning as well, allowing us insight into the how the world, or our own mind, works (or at least lets us to blow off steam about the randomness of it all).  Does laughter also have physiologic and therapeutic properties?

 

These are my principles; if you don’t like them, I have others- Grouch Marx

The beneficial effects of laughter have been known for many years. An early reference may be found in the Bible, “A merry heart doeth good like medicine” [Proverbs 17:22]. The modern concept of laughter as medicine was eloquently characterized by Norman Cousins, a noted author, professor, world peace advocate and nuclear disarmament activist in his 1976 New England Journal of Medicine article (and subsequent book by the same name), “Anatomy of an Illness (as Perceived by the Patient)”. He attributes laughter to curing his crippling rheumatologic disease, which doctors previously felt was irreversible. He states that 10 minutes of genuine belly laughter would relieve his arthritis and provide at least two hours of pain free sleep.  Mr Cousins’ writing spawned a series of studies on the effect of laughter leading to some interesting findings. In addition, it lead to the development of laughter clinics, including the Gesundheit community lead by Dr Patch Adams, where laughter is used to help patients with chronic, debilitating diseases find a way forward. 

 

What is the cardiologist’s favorite song? “Statin Alive” by the Bee Gees- Francisco Navarro

What effect does laughter have on the body?  Laughter has been shown produce numerous positive physiologic changes. Laughter relieves stress by decreasing stress hormones and by increasing endorphins (hormones that are usually released while exercising to make one feel good and to keep exercising).  It relaxes blood vessels, reduces blood pressure, decreases the heart rate and aids in muscle relaxation. Laughter improves the immune system and aids in healing after surgery.  A good laugh provides a huge psychological boost as well and helps to fight depression.  Humor is used routinely for stress reduction during cardiac rehabilitation programs. Lastly, if humor is injected into the doctor’s office visit, it will result in better patient satisfaction, greater patient empowerment and a stronger bond with the doctor. Most importantly, laughter and humor has no down side (except perhaps a pulled muscle from laughing so hard!).

 

Don’t trust atoms, they make up everything - Richard Feynman

Is there data to support laughter as medicine?  In a study from Norway spanning 15 years and including 53,000 patients, a good sense of humor lowered overall mortality for women and lowered mortality due to infections in both men and women. In a study of 17,000 people in Japan, those who a good hearty laugh more than once per week lived longer and had less heart disease than those who laughed only once per month or less. Laughter can also help with memory and thinking.  A strong laugh can stimulate the brain and lead to higher cognitive activity. Also, older patients had improved short-term memory and improved recall after watching a humorous video.

 

In summary, humor not only explains everything, but can help cure many ills. So for a long and healthy life, exercise 20-30 minutes a day, eat fresh fruits, vegetables, fish and plant based protein, sleep seven hours a night and socialize with friends and family. And it wouldn’t kill you to have a long, loud, hearty laugh each day too.

  

An Addition to the Cardiac Alphabet: “a” Novel Risk Factor

 

Lipoprotein (a) or Lp(a), pronounced “El Pee Little a”, is a lipid particle that is associated with plaque in the heart arteries, heart attack and cardiac death. What is Lp(a), what is its link to heart disease and how is it treated?

 

Lp(a) was discovered in 1963, but has been largely forgotten since then due to the lack of good treatment options.  Newer medications have shown some efficacy in lowering Lp(a) sparking a resurgence in research.  Plaque or blockage in the heart arteries mostly consists of low density lipoprotein (LDL, the “bad” cholesterol). In fact, plaque is more than 90% LDL cholesterol. Lp(a) however is also needed initiate and propagate plaque formation in the heart arteries. In addition, Lp(a) promotes blood clotting and inflammation, two properties contributing to heart disease. Abnormal elevation in Lp(a) is a common genetic entity. Lp(a) elevation above 50 mg/dl affects one in five people in the US or approximately 60 million Americans. Studies have linked Lp(a) to a higher risk for heart attack, stroke, aortic stenosis (thickening and blockage of  the aortic valve, limiting blood flow from the heart), heart failure, kidney disease and heart deaths.

 

Who should be tested for an abnormal Lp(a) level? Lp(a) may be measured in the blood and levels over 50 mg/dl are abnormal. However, the risk for heart disease increases as Lp(a) levels increase. Therefore, slight elevations may not be as clinically relevant as high levels of Lp(a).  There are a couple of scenarios where measuring Lp(a) may be beneficial. One consideration is in a patient with a strong family history for coronary artery disease (first degree relative with heart disease at age 60 or younger). Another possibility is a patient who has had recurrent heart events (heart attack or repeated cardiac stents) despite adequate treatment with a statin. In these cases knowing that there is an elevated Lp(a) level may change therapy. 

 

How should elevated Lp(a) be treated?  Ideally a medication should be chosen that reduces both LDL and Lp(a). Statins are the treatment of choice for patients with heart disease and high LDL levels. Statins lower LDL and reduce the risk for heart attack and cardiac death. Unfortunately, statins do not reduce Lp(a) levels. In fact, statins can increase Lp(a) by 10% to 20%.  Niacin reduces Lp(a) levels by 15-25%. Unfortunately, niacin has not been shown to reduce the risk for cardiac outcomes and has significant side effects (flushing of the skin after ingestion). For these reasons, niacin has not been used for heart patients for some time. PCSK9 inhibitors are new monoclonal antibodies that have very good data in heart disease. PCSK9 agents reduce LDL nearly 50% on their own and by 60% when used with a statin.  They have been shown to reduce the risk for heart attack and cardiac death. They are injected under the skin every two weeks and, since they are not a statin, do not have muscle pain as a side effect. In addition, PCSK9 agents reduce Lp(a) levels by 25%.  Another new medication is currently undergoing trials. Inclisiran reduces LDL by 50% and Lp(a) by 20%. It is also given by injection and is administered twice yearly. 

 

While the data associating Lp(a) with a higher risk for heart artery plaque, heart attack and cardiac death is well established, it is not known whether lowering Lp(a) will improve cardiac outcomes.  This is important because many treatments in cardiology that initially seemed promising (examples include vitamin E, hormone replacement therapy and folic acid) did not reduce the risk for heart attack or cardiac death when tested in large scale clinical trials and have thus fallen out of favor.  Trials are currently underway testing the Lp(a) hypothesis of heart artery disease and cardiac outcomes and the answer should be available very soon. Until then, we should try to identify patients who have significant elevations in Lp(a) and treat them as best we can. 

Q: Crazy Conspiracy Theory or Useful Supplement?

Over the past several months, the news has been reporting about a shadowy figure named “Q”, who has promulgated many baseless and false theories over a wide range of subjects, mostly about politicians and elections. Similarly, the body has a shadowy “Q”, coenzyme Q, which is ubiquitous and is involved in multiple metabolic pathways. Since the election is over, we will tackle questions about the body’s Q.

 

Coenzyme Q10 (CoQ10) is a naturally occurring substance produced by the body. It plays an essential role in generating energy for the cell. CoQ10 is found in abundance in tissues with high-energy requirements, such as the heart or skeletal muscle. CoQ10 is made in all tissues of the body and the pathway that produces it also produces cholesterol. In general, the body produces as much CoQ10 as it needs, but with aging, the levels of CoQ10 can diminish. Also, importantly, statin use can decrease CoQ10 levels.  CoQ10 is also available as a nutritional supplement with a global market estimated at $600 million. The supplement has been studied extensively and is safe with mild adverse reactions such as dizziness, insomnia, nausea and diarrhea. CoQ10 supplementation may play a role in statin associated muscle pain and in congestive heart failure.

 

Statin associated muscle problems can occur in 10 to 20% of patients who take statins to lower cholesterol. It is one of the major reasons why patients stop taking statins.  Symptoms range from minor muscle aches, to severe muscle pain, cramps and weakness, to muscle breakdown and toxicity (called rhabdomyolysis, a serious condition that can lead to hospitalization, kidney failure and even death).  Unfortunately, there is no objective test to determine statin associated muscle pain. A lab test, creatine kinase or CPK, can be elevated if there is muscle damage, but the test isn’t always reliable. The diagnosis is made by clinical symptoms and stopping the statin (if symptoms improve, they may have been due to the statin). No one knows the cause of statin associated muscle pain, but it has been hypothesized that depletion of CoQ10 may play a role. As such, many trials have been conducted to see if supplementation with CoQ10 would be beneficial. Unfortunately, the trials have been inconclusive and contradictory; some trials show that CoQ10 is beneficial while others do not.  One trial reported more muscle pain in patients who took a statin plus CoQ10 compared to statin plus placebo; a finding known as the nocebo effect. Even though benefit is questionable, there is no harm in taking CoQ10 supplements. Therefore, there may be a role. For patients with statin associated muscle pain the following may be an approach:

1)  Stop the statin for 1 or 2 months

2)  If symptoms improve, restart the same statin at a lower dose or try a different statin 

(if symptoms don’t improve, the muscle pains may be due to something else)

3)  If symptoms return at a low dose or on a different statin, a trial of CoQ10 may be used at a dose of 200 to 400 mg per day

 

Congestive heart failure (CHF) occurs when the heart weakens and cannot pump blood effectively. Fluid builds up in the lungs (causing shortness of breath) or throughout the body (causing swelling in the legs and abdomen).  CHF is the number one cause for hospitalization in the US. CoQ10 is involved with the production of energy in cells, especially heart cells. If CoQ10 is depleted, the heart cells will have reduced energy leading to the weakening of the pumping function of the heart. It has been shown that there are reduced levels of CoQ10 in the blood and in the heart tissue of CHF patients. It has been theorized that supplementation of CoQ10 might improve CHF.  Studies have shown that CoQ10 supplementation does improve symptoms, reduces hospitalizations and decreases cardiac death in chronic CHF patients.  It may also improve the ejection fraction (a measure of the heart’s pumping function). It must be noted that these studies are preliminary and that CoQ10 should only be used in the context of a clinical trial, and not for routine use as yet.

 

CoQ10 is emerging from the shadows and being extensively studied in heart disease.  Depletion of CoQ10 may play a role in statin associated muscle pain and in congestive heart failure.  While awaiting definitive data from future research, nutritional supplementation with CoQ10 may be beneficial in these conditions. It must be noted that CoQ10 is not approved for any medical condition by the Food and Drug Administration (FDA).  In addition, routine us of CoQ10 is not needed in cardiac patients as the body manufactures the amount of CoQ10 that it requires.

 

 

 

Can You Teach An Old Drug New Tricks?

 

It's a warm summer evening in ancient Athens. Archimedes is sitting in the agora and notices redness, swelling and pain in his big toe after drinking a kylix of wine. He goes to the market and is given an herb by a local farmer. After taking the herb, his big toe starts to feel better. He runs through the streets crying "Eureka!".

 

Colchicine is an anti-inflammatory medication which is used to treat acute episodes of gout. It is derived from the plant Colchicum autumnaleor autumn crocus. It was in fact used in ancient Greece, but as a laxative. The ancient Egyptians used it to treat rheumatism.  Colchicum plant extracts were used to treat gout starting about 550 AD. Benjamin Franklin, who suffered from gout, is credited with bringing Colchicum plants to the United States when he returned from Paris after completing his duties as French ambassador. Colchicine was first extracted in 1821 by French chemists and soon thereafter became a popular remedy for gout. It was approved for use in the US by the FDA in 1961. The anti-inflammatory effect of colchicine is very different from nonsteroidal anti-inflammatory (NSAID) medications and aspirin.  For more than 50 years colchicine was used exclusively to treat gout. Over the past ten years it’s anti-inflammatory properties were found to be useful in heart disease. Even more recently, it has been used in COVID-19. So colchicine, an old drug, finds itself at the intersection of inflammation, heart disease and COVID-19. Here are some clinical scenarios where colchicine has found new uses.

 

Pericarditis is inflammation of the sac lining the heart (the pericardium).  The most common cause of pericarditis is a virus, and symptoms are usually preceded by an upper respiratory infection, the flu or, recently, COVID-19.  Chest pain is the main presenting symptom, often associated with changes on the EKG or fluid around the heart on echocardiogram. Acute episodes of pericarditis are treated with anti-inflammatory agents such as aspirin, NSAIDs, colchicine or steroids.  Colchicine has been used since 1987 to treat acute pericarditis and recently it has been shown that colchicine combined with either an NSAID or aspirin was better for treatment than aspirin or NSAID alone.  With the combination, symptoms usually resolve within 72 hours, but treatment should continue for three months to prevent repeat episodes. About 15 to 30% of patients will have recurrent episodes of pericarditis. As with acute bouts, colchicine plus either aspirin or an NSAID successfully treats recurrent pericarditis. 

 

Coronary artery disease (CAD) or plaque in a heart artery can lead to a heart attack or chronic angina (chest pain). Low-grade inflammation within the walls of the heart arteries leads to plaque build up and blockage. Inflammation can also cause acute rupture of a plaque causing a heart attack. Previous research showed that a strong intravenous anti-inflammatory agent (a monoclonal antibody) improved outcomes for CAD patients but was expensive and had significant side effects. Would cheap, easily available colchicine be beneficial? Colchicine has been shown to reduce inflammation within the walls of arteries, so theoretically it should be helpful. Several studies examined the use of colchicine in chronic stable CAD patients and patients who had a recent heart attack. These studies show that colchicine consistently reduces the risk for cardiovascular outcomes (especially repeat heart stents).  Therefore, it seems that colchicine can be added to the cardiac medication armamentarium.

 

COVID-19 is another inflammatory disease. In severe COVID-19, the immune system’s inflammatory response overtakes the body affecting the lungs, heart, and blood vessels especially hard.  High dose, intravenous steroids are used to combat the inflammatory consequences of the disease.  Given colchicine’s anti-inflammatory properties, can it be used to prevent serious complications in outpatients with mild COVID-19? Several trials are underway to answer the question, one of which was recently reported. The trial enrolled 4000 patients with a diagnosis of COVID-19 within the previous 24 hours. In addition, one high-risk characteristic was needed (older age, obesity, diabetes, hypertension or underlying heart or lung disease).  Colchicine reduced hospitalizations, the need for a respirator and deaths. However, the trial was not peer-reviewed and with the sting of hydroxychloroquine fresh in mind, the data are being interpreted with caution. It is felt that colchicine may be beneficial, but that there is still insufficient evidence to use the medication.  Fortunately, other trials are ongoing and may be able to provide yet another use for colchicine.

 

Currently, a massive amount of research is being conducted focusing on inflammation, it’s effects on the body and novel agents to treat it. Meanwhile, the tried and true drug colchicine, with known efficacy, few side effects, wide availability and low cost, may be an answer to treat inflammatory diseases both old and new.

 

Red Meat, Red Flag?

The holidays are over. The gifts have been unwrapped. The decorations are down. The holiday ham has been cooked and eaten. Now that it’s a new year, it’s time to examine whether that ham is healthy or not.

 

For years, a cornerstone of teaching in medical school, and in cardiology training programs, is that red meat is bad for health.  Red meat is animal muscle and is defined as any meat that is a dark red color before it is cooked. It has been extensively studied for many years and has consistently been associated with higher risks for heart disease, cancer, diabetes and death. However, it is important to distinguish between unprocessed and processed red meat. Unprocessed red meat is defined as beef, pork, veal or lamb. Processed red meat is preserved in some way, by smoking, salting or curing. Examples of processed red meat include sausage, delicatessen meat (such as salami or ham or pepperoni), hot dogs and bacon.  Both types have similar amounts of cholesterol and saturated fat. Processed meat has slightly more calories and less protein per serving than unprocessed meat. The big differences between the two are the salt content and the preservatives. Processed meat has four times the amount of salt and many more preservatives than unprocessed meat.  So eating a sandwich with low fat deli meat may be less healthy than eating a juicy hamburger! Based on these differences, dietary guidelines have recommended low consumption of unprocessed red meat and avoidance of processed red meat. 

 

Then the tide changed in October 2019 when the Annals of Internal Medicine published a series of papers on red meat. They also published, and aggressively promoted, guidelines based on the findings.  These guidelines were contrary to the current dogma and stated that it was fine for Americans to continue their current consumption of both processed and unprocessed red meat. They stated, “No need to reduce red or processed meat consumption for good health”. This set off a media frenzy with headlines touting “It’s OK to eat red meat!”.  What the papers actually found was that the studies were of low quality and that the researchers could not say for certain that eating red meat was bad for health. One of the problems was that studies compared a red meat diet to other unhealthy diets (which were high in refined starches, sugars and saturated fats). Compared to these other unhealthy diets, consumption of red meat did not look as bad. Critics pointed this out as well as other numerous flaws in the data. In addition, it came to light that the authors did not disclose funding from the beef industry, which could have biased the results. The Annals then published a correction. 

 

So, is it OK to eat red meat? It certainly makes sense that red met increases the risk for heart disease. Red meat is associated with increased levels of LDL cholesterol (the “bad” cholesterol). Red meat is also high in iron, which has been show to increase the risk for heart attack and heart deaths. The high salt content of processed meats increases blood pressure and damages blood vessels. Lastly, preservatives such as nitrates are associated with heart artery disease. What if red meat was compared to a diet based on plant based proteins (such as nuts, peas, beans, or lentils)?  This study was performed and published in December 2020. Researchers followed 40,000 American men for 30 years and compared red meat to plant based protein. They found that one serving of red meat per day increased the risk for heart disease by 12%. One serving per day of unprocessed red meat increased the risk to 15%. Replacing red meat with plant-based protein lowered the risk for heart disease. If red meat was substituted with fish, yogurt, cheese or eggs, the risk of heart disease decreased by 15-24%. Replacing red meat with plant proteins was even more beneficial for those over 65 years old.  The bottom line was that increasing consumption of red meat proportionally increased the risk for heart disease. However, the key to a heart healthy diet may be less about reducing red meat and more about consuming plant based foods that protect the heart. We don’t know if the goal is eating less red meat or eating more plant based protein. 

 

What can be said about red meat consumption in 2021? It seems clear that processed red meats should be avoided. If unprocessed red meat is to be eaten, then limit consumption to about once per week.  It may be best to leave the ham to a once a year tradition.

 

The Vaccine

Has something been needling you the past year? Has something been jabbing at your brain? Has something pricked the bubble of your hopes and dreams for 2020? Of course! It’s COVID 19! Now, finally, there may be light at the end of the tunnel with the coronavirus vaccine. How does the new vaccine work and what does the data show?

 

Vaccines work by training the immune system to recognize and kill a foreign invader, such as a virus. Older vaccines work by injecting a dead virus or a weak live viruses to stimulate an immune response.  Newer vaccines work by injecting proteins found on the virus and teaching the immune system to mount a defensive response. Vaccines typically take years or even decades before they are ready to be used by the public. The development of a coronavirus vaccine is somewhat of a scientific miracle; the first COVID 19 case was described on December 1 2019, the coronavirus genetic code was sequenced on January 10 2020 and a vaccine was approved by the FDA on December 11 2020.  The coronavirus vaccine is not a single vaccine, there are at least six different methods companies are using to attack the virus.  Despite the quick turn around on the coronavirus vaccine, the technology behind it has been in development for decades. One method (the vaccine platform used by both Pfizer and Moderna) uses two key components: messenger RNA and the spike protein found on coronaviruses. Messenger RNA takes instructions encoded in the DNA into cells to turn on protein manufacturing. Messenger RNA vaccine technology was invented in the 1990’s and has been constantly refined since then. Work on a spike protein vaccine accelerated after pandemics with severe respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012, viruses that are similar to coronavirus. The vaccine, containing messenger RNA in a lipid shell, works as follows. The messenger RNA carrying a copy of the spike protein enters a cell. The cell reads the instructions for the spike protein and starts making copies of it.  The spike protein moves to the outside of the cell where the immune system detects it. The immune system then learns how to recognize the protein and releases defense mechanisms to kill the infected cells. The second method uses a viral vector (AstraZeneca, Johnson and Johnson and Oxford use this approach). The coronavirus spike protein is introduced into an adenovirus that infects only chimpanzees. The vaccine contains an empty adenovirus with the spike protein inside. This is injected and stimulates the immune system to recognize the spike protein and mount an immune response. Both vaccines teach the body’s own immune system to find and kill the coronavirus.

 

The data on Pfizer’s messenger RNA vaccine was just reported.  The trial enrolled 43,448 people, all 16 years of age or older.  The vaccine was administered in two doses, 21 days apart and patients were followed for two months. The efficacy of the vaccine in preventing symptomatic COVID 19 was excellent at 95%. The efficacy was good for all groups: 94% for those over 55 years old, 96% for men, 94 % for women, 95% for whites, 100% for blacks, 94% for Hispanics and 94% for those with hypertension. For comparison, the efficacy of the measles vaccine is 97%, the chicken pox vaccine is 82% and the flu vaccine varies from 50% to 60%. Side effects were generally mild and included pain at the injection site, fever, fatigue, headache and muscle or joint pain.  In general, reactions were milder and less common in older patients (> 55) compared to younger patients.  Reactions were more common after the second dose compared to the first dose. Side effects are similar to the reactions seen after the shingles vaccine.  It is not known whether the vaccine can prevent COVID 19 in children under 16 years old, pregnant women and immunocompromised patients. In addition, the study could not determine whether the vaccine prevents asymptomatic infection. Lastly, patients in the placebo arm will have to be offered the vaccine since the FDA approved it. It is unethical to withhold vaccine for these people. This means that long-term efficacy and safety will be determined by real world experience. Based on this data, the FDA gave the Pfizer vaccine emergency use authorization on December 11 2020. The first dose of this vaccine was given to a 90-year-old woman in England on December 8 2020.  Moderna is conducting a 30,000 person trial with a similar vaccine. The preliminary results show good efficacy (also 95%) and safety but the final results are still pending. 

 

The Oxford adenovirus vector vaccine was studied in 23,849 people over the age of 18. This was also a two-dose regimen. The efficacy was 62% in patients who received two standard doses and 90% in those who received a low dose followed by a standard dose. The side effect profile was also very low.  Johnson and Johnson’s vaccine works in a similar fashion.  A 60,000 person trial was put on hold due to a serious adverse reaction but has recently resumed. Results from the trial are pending. 

 

To contain coronavirus, it is estimated that 60% of the population will need to be vaccinated to achieve herd immunity.  This may be difficult for several reasons. First, enough vaccine must be manufactured and distributed. There are many logistical obstacles. Next, enough people must consent to take the vaccine.  A recent poll of Americans found that 29% would definitely take the vaccine and 31% would probably take it. That adds up to 60% with no room for error. In addition, a poll among health care workers in New Jersey revealed only 50% were planning on taking the vaccine. This is disappointing since the CDC guidelines will have health care personnel vaccinated first along with long term nursing home residents in Phase 1a.  Phase 1b will be essential workers (police, fire, corrections officers, transportation workers, food and agriculture workers and teachers). Phase 1C will include adults with high-risk medical conditions and adults over age 65. 

 

Some caveats:

The efficacy of the vaccine is excellent (better than the annual flu vaccine with an efficacy of only 50-60%). 

It seems that the vaccine-induced immune response is stronger than that of the natural COVID 19 infection.

The side effect profile is similar to other vaccines (such as the shingles vaccine). 

The coronavirus is not being injected. You cannot get COVID 19 from the vaccine.

The vaccine will not alter your DNA.

 

So once it is available, please line up to get your vaccine. It will help your herd tremendously.