Monday, June 6, 2022

The Calcified Aortic Valve

 


The aortic valve is a three-leaflet valve situated between the left ventricle (the main pumping chamber of the heart) and the aorta (the main artery leading from the heart). When the left ventricle contracts to send blood to the body, the aortic valve opens to allow the blood to flow out. After the blood is ejected, the valve closes to prevent blood from leaking back in to the heart. The aortic valve opens and closes, under a tremendous amount of pressure, with each heartbeat, for our entire lives. Because of this, the aortic valve is subject to “wear and tear” over time. As the valve wears down, the leaflets become thickened and calcium is deposited to repair microtears in the valve.  As the valve becomes more thickened and calcified, it doesn’t open fully, restricting the blood flow from the heart. This pathologic condition is called calcific aortic stenosis. When there is significant restriction of the blood flow, it is called severe aortic stenosis. Severe aortic stenosis may cause chest pain, passing out, congestive heart failure or sudden cardiac death. Unfortunately, once severe symptomatic aortic stenosis occurs, there is no medication to treat it. The only way to restore blood flow is to replace the valve. This is done by surgically removing and replacing the aortic valve or, more recently, the valve can be replaced without surgery by inserting a new valve through the artery in the groin (TAVR). Currently there are no medications that can prevent calcific aortic stenosis or slow its progression once it occurs. Or is there?

 

Calcific aortic stenosis is very common occurring in 2% of people over the age of 65 and 4% over 85 years old. It is associated with older age and shares other risk factors for atherosclerosis (blockage in the heart arteries). It has been known for some time that plasma lipids (cholesterol) are involved in the process of thickening and calcification of the aortic valve. It seems reasonable to presume that if elevated cholesterol is a risk factor that lowering cholesterol with a statin would halt the process. Many studies with statins have been performed. Unfortunately, statins do not halt the progression of severe calcific aortic stenosis. What if a statin is started before the disease is far advanced? Again, statins did not slow the progression in patients with mild aortic stenosis.  So, lowering cholesterol doesn’t work. Are there other targets? One possibility is PCSK9. PCKS9 is a protein involved in the production of LDL cholesterol. In patients with heart artery disease PCSK9 inhibitors (such as Praluent or Repatha) dramatically lower LDL cholesterol and reduce the risk for heart attack and cardiac death.  Recently it has been shown that patients with calcific aortic stenosis have higher levels of PCSK9. It is felt that PCSK9 plays a role in mediating aortic stenosis through inflammation and the stress responses of the cell. Do PCSK9 inhibitors slow the progression of calcific aortic stenosis? We don’t know, but future trials may give an answer. Another possible target is lipoprotein a. Lipoprotein a is an LDL like particle that is also associated with elevated risk for heart artery disease. Elevated levels of lipoprotein a have been shown to correlate with progression of calcific aortic stenosis as well. Patients with the highest level of lipoprotein a were twice as likely to need aortic valve replacement as patients with low levels of the protein. Statins do not lower levels of lipoprotein a, but PCSK9 inhibitors do. Whether this translates to a beneficial effect for calcific aortic stenosis is not known, but it seems a trial with these agents is badly needed. 

 

Another potential target is cardiac amyloid. What is amyloidosis? The pathogenesis of amyloid involves a protein called TTR which is produced by the liver and aids in transporting thyroid hormone. In some people (older patients, patients with genetic predisposition), TTR clumps together to form amyloid fibrils. These amyloid fibrils are deposited in many tissues in the body, but especially the brain, the nerves and the heart.  Amyloid deposition in the heart can cause a variety of problems including congestive heart failure as well as calcific aortic stenosis. In patients older than 75 years old with aortic stenosis, 14% have cardiac amyloid.  Cardiac amyloid is treated with a medication called Tafamidis, which stabilizes TTR and prevents the formation of amyloid fibrils. Tafamidis slows the progression of cardiac amyloid in patients with congestive heart failure, but it is not known whether it does the same for calcific aortic stenosis. This too may be a promising area and ripe for future research. 

 

Another potential target is calcium. Since calcium is deposited in the aortic valve do calcium supplements increase the risk? A study of 2600 patients with mild to moderate aortic stenosis found the following. Aortic valve replacement was ultimately needed in 50% of patients taking calcium supplements versus only 11% in patients not taking supplements. It was concluded that long-term calcium supplementation should be avoided in calcific aortic stenosis. 

 

If you have calcific aortic stenosis, don’t despair. A newer and better treatment (TAVR) has already dramatically changed the life for many a patient with this disease.  Although we currently cannot stop calcific aortic stenosis or alter its progression, newer targets and newer treatments may be on the horizon offering similar dramatic medical options to improve the lives of patients. In the meantime, hold those calcium supplements. 

 

Tuesday, May 10, 2022

April Showers Bring May Green Prescriptions

 


As the rain in April turns into the beautiful trees, shrubs, grass and flowers of May, we can see that green is good!  As we sit gazing out of our window at the marvelous greenery, we wonder, “Is it better to exercise indoors in a gym or outdoors in nature? How else is green good for health?” The US Environmental Protection Agency has estimated that Americans spend 90% of their time indoors. Is this healthy? Should we heed our mothers’ advice and “Go outside and get some fresh air”?

 

It has been felt for a long time that getting back to nature, spending time in natural environments, had positive mental and physical effects.  Being outside supposedly lowered blood pressure, decreased obesity, helped with diabetes, reduced anxiety and depression, lessened stress, and promoted physical activity while combating sedentary leisure time. Because of these effects, doctors have given out nature prescriptions, essentially encouraging patients to get outside. There is even a Japanese practice called “forest bathing” (shinrin-yoku) whereby health benefits are obtained just by sitting in nature. Is there any data to support these health claims? One study of forest bathing showed that the practice increased natural killer cells and other cancer fighting proteins. Researchers theorize that the trees emit compounds that help plants fight disease, but apparently also help humans fight cancer as well. Another study showed that exercising in natural environments reduced stress, decreased anger, lessened depression and improved energy compared to exercising indoors. A different study compared a three-hour mountain hike with walking on treadmill indoors and with sedentary activities. Mountain hiking improved a variety of psychological parameters compared to the treadmill and sitting indoors.  A 2019 study looked at nearly 20,000 people in England and found that spending two hours per week in green spaces (parks or other natural environments) improved people’s health and psychological well-being.  The two hours could be all at once or spread over the week.  The two hours also held for those who were ill or disabled, suggesting the time in nature was the key rather the effect of healthier people outside exercising more often.  It seems that exercising outside, in a natural green space, is better than indoors. Even if the data isn’t entirely true, there is no downside risk to being outside except for encountering a few raindrops now and then.

 

How about living near green spaces? Is there a health benefit? One study looked at the green space of Toronto.  They found that people who live in areas with more trees had less hypertension, diabetes, heart attacks and stroke. They found that having 11 or more trees in a city block reduced the risk for cardiac disease.  In addition, researchers looked at NASA images of the United States and categorized each county’s greenness (a measure of trees, shrubs and grass). For every 0.1 unit increase in greenness, deaths from heart disease fell by 13 deaths per 100,00 people. This was confirmed in a study from Spain.  People who live near green spaces had a 16% reduction in their risk for stroke. The mechanism of benefit of green spaces may be the lower amount of air pollution and better air quality in general in these areas. Green is good!

 

Another type of green is good for overall health. Green leafy vegetables (for example, arugula, green beans, kale, spinach, asparagus, broccoli, zucchini) have significant health benefits.  Three servings a day reduced the risk of diabetes by 13% and lowered the risk for heart disease by 24%. Now there is new information about a different green. Add avocado to the list of healthy greens. People who ate two avocados per week had a 22% lower risk for developing cardiovascular events.

 

How can we put all this greenness to work for us? With a Green Prescription. The prescription itself is more than just a ticket to get medication at the pharmacy. It is a contract between the doctor and the patient. With that in mind, here is your contract with your doctor and with nature, the Green Prescription: 

1) Spend 120 minutes per week outdoors in nature

2) Eat 3-4 servings of green leafy vegetables per day

3) Have 2 avocados per week

Munching on an avocado and some celery sticks while hiking through the forest is optional.

 

Tuesday, April 5, 2022

The Intersection of Breast Cancer and Heart Disease

(Google Images)

A 69-year-old woman presents to her cardiologist with shortness of breath.  She was diagnosed with congestive heart failure (CHF).  An echocardiogram showed an ejection fraction (a measure of the pumping function of the heart) of 25%, representing a severe weakness of the heart muscle. Her past medical history is remarkable for left sided breast cancer diagnosed in 2000. She was treated with lumpectomy and chemotherapy.  She was felt to be cancer free in 2008. What caused her CHF and her weak heart?

 

Breast cancer is the most common form of cancer in woman in the United States. Approximately 1 in 8 women will develop breast cancer.  Breast cancer does occur in men as well, although it is rare, accounting for only a few cases per year.  Breast cancer is treated with surgery, radiation therapy and chemotherapy.  Fortunately, cancer treatments are curing more and more breast cancer. Unfortunately, those same treatments can cause heart disease, often years later.  Radiation, especially to the left side, can affect all of the layers of the heart. It can affect the outer layer of the heart causing inflammation and chest pain (pericarditis). Radiation can damage the heart muscle and cause it to weaken. Lastly, radiation can cause blockage in the heart arteries. Studies have shown that patients who had radiation for left-sided breast cancer are twice as likely to have heart artery disease as patients with right-sided cancer.  Radiation can accelerate blockage starting about 5 years after therapy and the effect may persist for up to 30 years. Chemotherapy agents are very good at inducing cures, but two agents in particular can cause significant heart damage. Adriamycin acts as a toxin to the heart muscle. It causes weakening and a reduction in the ejection fraction, leading to CHF, often 10 to 20 years after the chemotherapy is given. Unfortunately, Adriamycin’s effect is irreversible. Another agent, Herceptin (Trastuzumab) also causes a weak heart muscle and CHF. However, stopping the agent does allow the heart to recover function, so vigilance is needed during its administration. 

 

Breast cancer and heart disease share a number of risk factors including: older age, poor diet, alcohol use, obesity, sedentary lifestyle and smoking. In a two for one deal, exercising, keeping weight down, not smoking and limiting alcohol not only reduces the risk for heart disease, but also lowers the chance of getting breast cancer. This advice is valid for both women and men (remember, men can get breast cancer as well). Two strategies in particular are worth noting for their reduction in both heart disease and breast cancer: exercise and taking a statin for cholesterol.  Exercise capacity has shown to be a prognostic factor in breast cancer.  Patients with higher levels of physical activity have a lower risk of developing breast cancer and dying from the disease.  Patients with better cardiorespiratory reserve, developed from years of exercising, can tolerate the toxic effect of chemotherapy. These patients suffer less cardiac side effects during treatment. In addition, these patients are more likely to stay active during chemotherapy, thus lessening their risk further. Statins may be protective as well. Women who were taking a statin during chemotherapy had a lower risk for CHF. This may be because, beyond lowering cholesterol, statins decrease inflammation and stress in heart cells. 

 

Screening for breast cancer may be a useful tool for screening for heart disease too. The mammogram (an X-ray of the breast) is the standard test for screening for and detecting breast cancer.  If a suspicious area is seen on mammography, then a biopsy is done to confirm or rule out cancer.  Breast artery calcification may also be seen on mammography. Breast artery calcification, like heart artery calcification, signifies the presence of plaque or blockage in the arterial wall.  Heart artery calcification on CT scan is associated with a higher risk for heart attack and heart death and a reason to intensify preventive treatments.  Does breast artery calcification have the same prognostic significance? In a study of 5000 women (all over age 60) who did not have breast cancer or heart disease, 26% were found to have breast artery calcification. Those with calcification were twice as likely to have heart disease or stroke. In another two for one deal, it looks like mammography can screen for bother breast cancer and heart disease. 

 

The index case and the three intersections between breast cancer and heart disease teach us the following lessons. Patients who have had breast cancer and who had radiation or certain types of chemotherapy must remain vigilant about heart symptoms and see their doctor if symptoms do occur.  With common risk factors, following a healthy lifestyle reaps rewards in numerous ways. Lastly, artery calcification anywhere in the body must be taken seriously and preventive medications must be initiated.  Following these measures can help avoid two deadly diseases: breast cancer and cardiovascular disease.



 

Tuesday, March 8, 2022

Cholesterol-Years


Let’s evaluate the cardiovascular risk for three hypothetical scenarios. 

A 50-year-old office worker who, prior to the pandemic, was not overweight and had normal cholesterol levels. He has no family history for heart disease. During the pandemic, he worked from home, stopped exercising, did not watch his diet and gained 25 pounds. 

A 50-year-old construction worker who has had high cholesterol all of his life, but has not been on medication. His father and brother both had heart attacks in their fifties. During the pandemic, he was active at work, exercised on the weekends and didn’t gain any weight. 

A 65-year-old woman who did not have high cholesterol until menopause. She has no family history of heart disease, is active and eats a Mediterranean diet. 

All three recently had blood work and the results are the same; cholesterol 250, HDL cholesterol 30, LDL cholesterol 135. All three are nonsmokers, do not have diabetes or high blood pressure and are not taking a statin. Entering their information into the American College of Cardiology (ACC) risk calculator yields similar results: they each have a 7.2% risk for a heart attack or stroke over the next ten years. Even though their cholesterol numbers and their risk levels are the same, is the risk for heart disease the same for all three people?

 

Unfortunately, the ACC risk calculator does not factor in family history of heart disease.  It has been known for quite some time that having a first degree relative with heart disease at an early age is a strong risk factor for heart disease.  One of the reasons for premature heart disease in families is a genetic tendency for high cholesterol, especially elevated levels at an early age (a condition known as familial hyperlipidemia). Premature heart disease is a major consequence of familial hyperlipidemia.  Familial hyperlipidemia is suspected in a patient who has: 1) heart or vascular disease at a young age (for men under the age of 55, for women under 60); 2) a family history of vascular disease at a young age;  3) tendon xanthomas (cholesterol deposits on tendons - pictured above); 4) a very high LDL cholesterol (over 155 and often in the 200 to 300 range).  Why do people with familial hyperlipidemia develop blockage in heart arteries earlier than those who don’t have this condition? The answer is that the plaque forming effect of LDL cholesterol is dependent on both the level of LDL and the duration of elevation. The risk for heart artery disease can be expressed in “cholesterol-years” or the average LDL level times the number of years of exposure (this is similar to a core concept in cardiology, pack years, the average number of packs of cigarettes smoked times the number of years smoked). Plaque begins to form in the heart arteries after a certain threshold of LDL exposure is reached.  For example, a person can have an average LDL level of 100 mg/dl for 70 years resulting in 7 grams/dl cholesterol-years. If 7 grams/dl is the threshold for developing plaque then they will manifest heart artery disease at age 70. On the other hand, a person with familial hyperlipidemia may have an average LDL of 200 mg/dl, reach 7 grams/dl cholesterol-years and develop heart issues at 35 years old. The theoretic threshold for developing disease is lower if there is hypertension or diabetes. The threshold will be higher if a healthy lifestyle keeps LDL lower for longer.

 

The concept of cholesterol-years may explain why women manifest heart disease at later ages than their male counterparts.  It is well know that women have low levels of heart disease (compared to men) until they hit menopause. After menopause, the rate of cardiac disease accelerates exponentially. This is because total cholesterol and LDL go up dramatically in the year after the onset of menopause. Due to the protection afforded women by their hormones before menopause, their cholesterol-years or their years of LDL exposure are less than men (especially in their teens, twenties and thirties) and therefore heart disease is shifted towards older age (when their cholesterol-years catch up to men).

 

With this information in mind, let’s rank the scenarios. The 50-year-old office worker has the lowest risk for heart artery disease. His cholesterol only went up over the past two years. He has a low number of cholesterol-years and a lower lifetime exposure to LDL than his counterparts.  He should initiate lifestyle changes immediately. The 65-year-old woman has the next lowest risk. Her cholesterol was low until menopause, rising to high levels over the past 10 years. She has been following a good diet and exercising, so she may need to be started on a statin. The 50-year-old construction worker with familial hyperlipidemia has the highest risk. He has about 6.7 grams/dl cholesterol-years (average LDL 135 mg/dl over 50 years) and should also be started on medications immediately. 

 

The cholesterol-years approach is a measure of exposure over time and better than relying on a single measurement of LDL. This concept also favors intervening to lower cholesterol at an earlier age, say ages 18 to 30, with lifestyle alterations or medications to protect against cardiac disease later in life. 

Tuesday, February 15, 2022

The Sunshine Vitamin and the Heart


A 65-year-old woman is seeing her cardiologist for follow up of an elevated heart artery calcium score on CT scan.  They discuss various treatment options including starting a statin. She asks, “Should I continue to take my Vitamin D and calcium supplements since there is higher than normal calcium seen in my heart arteries?” How do vitamin D, calcium and their supplements affect the heart?

 

Vitamin D is necessary to maintain bone health and strength.  Vitamin D is also an integral part of normal cell metabolism.  Vitamin D receptors are present in almost every tissue in the body and vitamin D plays a role in regulating cell growth. Vitamin D is obtained by the body through 2 avenues: external sources (food and supplements) and internal sources (produced by the body). Vitamin D can be obtained from the diet (there are a few food sources that naturally contain vitamin D such as oily fish, liver, egg yolks, and vitamin D fortified milk) or by supplements. Vitamin D supplementation is becoming more and more widespread. Between 2011 and 2014, about 37% of the US population took a vitamin D supplement. In the same time period, 61% of adults over age 65 used a vitamin D supplement. Vitamin D can also be produced by the body. The skin turns ultraviolet rays from the sun into vitamin D (thus the name, “The Sunshine Vitamin”). The skin production of vitamin D depends on climate, skin pigmentation, sun exposure and age. Risk factors for low vitamin D levels include older age, colder climates, reduced outdoor activity, and sunscreen use. 

 

Vitamin D levels in the blood can be measured. Vitamin D deficiency is defined as a vitamin D concentration of < 20 ng/ml. Levels of vitamin D between 20 and 29 ng/ml is considered insufficient. The optimal vitamin D level is > 30 ng/ml.  Vitamin D deficiency can cause weak bones and fractures. It is associated with diabetes, autoimmune disorders and rheumatoid arthritis. Vitamin D deficiency can also cause heart problems by increasing inflammation, increasing blood pressure and causing arteries to stiffen. Studies have shown that low levels of vitamin D can increase the risk for heart artery disease, heart attack, stroke and congestive heart failure. Do vitamin D supplements mitigate the risk of low vitamin D levels? The effects of vitamin D on fractures and bone health is uncertain. A recent review showed that vitamin D supplementation does not prevent fractures or improve bone mineral density.  In addition, well-designed trials show that vitamin D supplements do not benefit heart health.  Lastly, vitamin D supplementation does not reduce the risk for cancer, stroke, high blood pressure or dying. Vitamin D supplementation is safe at levels up to 2000 IU/day, however at 4000 IU/day or more toxicity can occur. Vitamin D supplementation does not appear to be harmful to the heart, even at higher levels. 

 

Calcium is the most abundant mineral in the body, with 99% of the body’s calcium stored in the bones and teeth. Adequate calcium intake is essential for bone development and maintenance. Because of their effects on bone health calcium and vitamin D are intricately intertwined. Like vitamin D, calcium can be obtained either in the diet or via supplementation (it is not naturally produced by the body).  Food sources of calcium include leafy green vegetables, low-fat diary products, beans and almonds. The recommended dietary intake of calcium for adults 19 to 50 years old and men 51 to 70 years old is 1000 mg/day. For women 51 to 70 years old and for men and women older than 70 it is 1200 mg/day. Age, vitamin D and other factors influence calcium absorption by the body. People at risk for inadequate calcium intake include those with lactose intolerance and postmenopausal women.  Calcium supplementation is very common with use by 40% of the general US population and more than 65% of postmenopausal women. Calcium supplementation does reduce the risk for bone fractures.  Unfortunately, calcium supplements do appear to increase the risk for cardiovascular events, such as heart attack and stroke, especially at levels over 1400 mg/day. Calcium supplement users also had an increased risk for heart artery calcification compared to those not on supplements.  Of note is the fact that higher intake of calcium in the diet was not associated with increased heart risks. 

 

What are the recommendations for vitamin D and calcium as well as the use of their supplements?  For the general population, obtain vitamin D from food sources and from sunlight. If vitamin D insufficiency persists despite diet and outdoor activity, then supplementation can be used. Calcium recommendations are similar; obtain calcium through the diet and increased physical activity. If calcium deficiency persists or there are increased needs, calcium supplements can be used, keeping in mind that there is a possibility of cardiovascular harm. For both vitamin D and calcium, pill-based supplements may not be better than a healthy life style, including a prudent diet and physical activity.

 

What should we tell our postmenopausal woman with an elevated coronary calcium score about her supplement use? There should be a frank risk/benefit, shared decision making conversation.  Vitamin D supplements are neutral; they don’t seem to confer any benefit for heart health, but they are not harmful either.  Calcium supplements help with bone health, but may come with added cardiac risks, including the possibility of worsening her coronary calcium.  The supplements can cautiously continue as long as there is an understanding of the risks and benefits and with close monitoring. 

Tuesday, January 11, 2022

The Eyes Have It



William Shakespeare once said, “The eyes are the window to your soul.” This is poetic and philosophical, but can the eyes be more practical and be a window on the heart as well? A cataract is a common eye disorder that occurs as people get older. Are cataracts associated with heart disease or a higher risk of dying? Could a cataract be a new risk factor for cardiac disease?

 

A cataract is a clouding of the lens in the eye.  The eye uses a natural lens to alter the light coming into the eye to help us see.  With aging, the proteins in the lens start to break down, causing vision to become cloudy, like looking through a foggy or dusty windshield.  Aging is the most the common cause of a cataract. People over 60 years old may start to have clouding, although severe symptoms may not develop for years.  Aside from older age, other risk factors for cataracts include diabetes, smoking, heavy alcohol use, hypertension, working in direct sunlight, certain medications such as corticosteroids and a family history of cataract. Once symptoms become severe, the treatment is surgery. An eye doctor can replace the cloudy lens with a clear artificial lens and restore sight. Cataracts are quite common and a major cause of visual impairment worldwide.  Approximately 90% of Americans over age 65 will develop cataracts and 4 million cataract surgeries are performed each year in the United States.  

 

Are cataracts associated with heart disease or a higher risk of dying? Many studies have been done to try to answer these questions, with conflicting results.  More recent data points to an association between these processes. The Nurses Health Study followed 60,000 women, aged 45 to 63, for 10 years. The study found that cataract extraction significantly increased the risk of dying from heart disease. A recently published study looked at 15,000 Americans over the age of 40 with a follow up of 10 years.  This study found significant associations with cataract surgery and the risk of dying. Patients who have had cataract surgery had a 13% higher risk of dying from any cause and a 36% higher risk of dying from heart disease. Lastly, a study from Israel showed that cardiovascular disease was significantly more prevalent in cataract patients undergoing surgery. 

 

How are cataracts and heart disease connected? There are several possible unifying mechanisms. Cataracts and heart artery disease share some common risk factors, such as older age, hypertension, diabetes and smoking. Oxidative stress causes damage and break down of the proteins in the lens. Of course, stress also causes plaque and blockage in the heart arteries. Another mechanism involves proteins in the lens called crystallins. These proteins are present throughout the body and help regulate the body’s response to inflammation and ischemia (low blood flow). The break down of these proteins in the eye and throughout the body may a more widespread systemic disorder rather than a localized problem involving just the eye. Lastly, both cataract and heart patients are more prone to depression.

 

Does this mean that cataracts are a new risk factor for cardiac disease? Not necessarily. Both cataracts and heart disease are common problems and both occur as we get older. It is possible that the both conditions are a consequence of ageing or some other systemic process and not causally related. The research doesn’t show that cataracts cause heart disease. Even so, it seems prudent for patients with cataracts to keep an eye out for symptoms of heart disease and see their doctor quickly if symptoms develop.

Tuesday, December 7, 2021

NASH


Candy is dandy, but liquor is quicker

 

How easy for those who do not bulge, to not overindulge

- Ogden Nash

 

Ogden Nash was a famous American poet and humorist.  Unfortunately the NASH to be discussed in this column is not as well known and certainly is not humorous. 

 

NASH (or non-alcoholic steatohepatitis) is a subcategory of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common chronic liver disease, affecting about 25% of adults worldwide.  It occurs when fat builds up in the liver, without associated liver damage. It can progress to NASH, which is a fatty liver but with inflammation, liver injury and scarring (fibrosis).  NASH is quite serious and can lead to cirrhosis (liver failure) or liver cancer. NASH is the most common reason for liver transplantation. About 20-30% of patients with NASH progress to cirrhosis or cancer.  NASH is seen in about 3-5% of people around the world. NAFLD is the liver manifestation of the metabolic syndrome (a systemic condition characterized by obesity, diabetes, high blood pressure and abnormal lipids, especially high triglycerides and low HDL).  Because of this association, NAFLD is linked to cardiovascular disease and both conditions are considered the end-organ damage of the metabolic syndrome.  NAFLD is diagnosed by liver ultrasound or liver biopsy, both methods show the fatty infiltration of the liver. Liver enzymes in the blood (alanine transaminase, ALT, and aspartate transaminase, AST) are mildly elevated. To make the diagnosis, daily alcohol consumption must be less than 30 grams in men and 20 grams in women per day (for perspective one glass of wine is about 17 grams).

 

There are several mechanisms linking NAFLD and cardiovascular disease.  In NAFLD, a diet high in cholesterol and saturated fat leads to high triglycerides in the blood and fat deposition in the liver. The same high triglycerides and low HDL cholesterol cause plaque build up in the heart arteries and blockage.  In diabetic patients with metabolic syndrome, persistently high sugar levels lead to vascular inflammation and coronary artery disease. Fat is present in the liver, but is also deposited around the heart.  The heart arteries run through this fatty tissue, exposing them to inflammation and subsequent blockage.

 

NAFLD is associated with higher mortality compared to the general population.  With more advanced disease (more fibrosis, cirrhosis, cancer) the higher the death rate.  Patients with NAFLD are also at higher risk for developing heart attack, stroke, angina (heart related chest pain) or cardiac death.  Patients with more advanced disease (especially more severe liver fibrosis) are at higher risk for developing cardiovascular disease. Because of this, all NAFLD patients should be evaluated for their risk for heart disease. 

 

NAFLD is treated with weight loss, exercise, diet and medication. A total body weight loss of about 10% is needed to reverse the liver fibrosis. However, weight loss alone is not sufficient to reduce the cardiac risk for NAFLD patients, other lifestyle modifications are necessary. Exercise is needed and the recommended amount is 150-200 minutes per week of moderate exercise. This includes both aerobic activity (“cardio”) and resistance (weight training).  Following a diet high in calories, saturated fats, and refined carbohydrates can lead to obesity, type two diabetes, NAFLD, metabolic syndrome and cardiovascular disease. In addition, consuming sugar-sweetened beverages that are high in fructose (a type of sugar) produces the metabolic syndrome.  Patients with NAFLD should restrict foods high in fructose, saturated fats and simple carbohydrates. Following a Mediterranean diet was shown to reduce the fat in the liver. In addition, the timing of food consumption is a factor. Intermittent fasting, with no food intake for 10 to 16 hours, helps reduce unhealthy metabolic abnormalities. This strategy involves eating during the day with nothing consumed after 6 PM.  Medications may also be beneficial for reversing NAFLD. In patients with concomitant diabetes, metformin and sodium glucose linked transport inhibitors (SGLT2 agents, such as Jardiance or Farxiga) reduce fat accumulation and decrease inflammation. These agents also reduce the risk for heart attack and congestive heart failure in diabetics. All patients with NAFLD should have their cholesterol lowered with statins. This has been proven to be safe and effective in NAFLD (despite the mild liver enzyme elevation).  Lastly, new agents that block key metabolic, inflammation and fibrosis pathways in NAFLD are being developed.

 

So, the cardiologist’s retort to Ogden Nash is that liquor may be quicker, but candy is not benign. Enjoy the holiday season, but try to limit the candy, fatty foods and sugar-sweetened beverages.  And no matter what your weight, try not to overindulge. Your heart and your liver will thank you.