More Feathers in the Cap of Icosapent Ethyl

I am reminded of my late mentor, Dr. Peter O. Kwiterovich, Jr. who used to say when we published new research findings that “this is another feather in your cap”! Well, this expression could not be truer than what we have been witnessing with icosapent ethyl (IPE), the highly purified omega-3 fatty acid, EPA. First there was the landmark study, REDUCE-IT where IPE reduced the risk of cardiovascular death, heart attack, stroke, bypass/stent placement and rehospitalization for unstable by an astounding 25% in statin treated men and women with high triglycerides and cardiovascular risk. To date, IPE remains the best treatment for patients at similar underlying risk.

Last week, 2 new feathers were added to the IPE cap during presentations at the European Society of Cardiology (ESC), one of medicine’s premier international meetings. The first paper presented by my colleague, Dr. Deepak Bhatt found IPE to reduce the risk of the 2 types of heart attacks (ST and non-ST elevation) by 40% and 27%, respectively. The second feather was the result of another analysis showing that IPE eradicated the excess risk of cardiovascular events attributable to cigarette smoking; the manuscript is published in the European Heart Journal Cardiovascular Pharmacotherapy. For a comprehensive review of other IPE “feathers”, check out the excellent new review by Dr. Prakriti Gaba published in JCL.

During an ESC presentation, the prominent Danish Professor and Lipid Expert, Dr. Borge Nordestgaard, commented to me that every analysis performed for IPE has shown strikingly positive results. Could the reason for IPEs success be that the compound has unique characteristics that other fatty acids don’t? In fact, my colleague Dr. Preston Mason has performed a number of elegant studies demonstrating that to be the case. Specifically, IPE reduces inflammation and oxidative stress while improving endothelial function.

You certainly don’t have to convince me that IPE acts different fatty acids. Decades ago, we examined the role of purified EPA in human cells and found favorable effects that were not observed with other fatty acids- perhaps a presage of good things to come for IPE.

Michael Miller, MD is a cardiologist and Chief of Medicine at the Corporal Michael J Crescenz VA Medical Center and Vice Chair of Medicine at the Hospital of the University of Pennsylvania. Prior to his arrival in Philadelphia, he was Professor of Cardiovascular Medicine, Epidemiology and Public Health at the University of Maryland School of Medicine. He is the author of numerous scientific publications and several books, including Heal Your Heart published by Penguin Random House. Check him out on twitter: @mmillermd1

30 Years of Heart-Related Discoveries/Advances at the University of Maryland School of Medicine

As my 30-plus years as a faculty member at the University of Maryland School of Medicine and Medical Center has drawn to a close, I fondly recall 10 heart-related findings/discoveries and newsworthy events that gained worldwide attention, ending with the first genetically altered pig heart transplanted at UMMS last week.  Here they are in no special order.

1.         Poe likely died of rabies, doctor’s review shows: https://www.baltimoresun.com/news/bs-xpm-1996-09-11-1996255015-story.html

2.         Having high cholesterol levels early in life leads to heart problems by middle age: https://www.eurekalert.org/news-releases/823756

3.         Air Pollution and Diabetes: https://www.loe.org/shows/segments.html?programID=14-P13-00002&segmentID=5#:~:text=We’ve%20long%20known%20that,fatty%20diet%20can%20promote%20diabetes.

4. U.S. Amish gene trait may inspire heart protection: https://www.reuters.com/article/us-heart-gene/u-s-amish-gene-trait-may-inspire-heart-protection-idUKTRE4BA6JQ20081211

https://www.loe.org/shows/segments.html?programID=14-P13-00002&segmentID=5

5.         Want a McMuffin? Take your McVitamins: https://greensboro.com/want-a-mcmuffin-take-your-mcvitamins/article_20be3661-d342-549f-9118-a2e355f4175a.html

6.         UMMC Implants the World’s Smallest Pacemaker: https://www.umms.org/ummc/news/2017/ummc-implants-the-worlds-smallest-pacemaker

7.         University Of Maryland School of Medicine Study Shows Laughter Helps Blood Vessels Function Better: https://www.sciencedaily.com/releases/2005/03/050309111444.htm

8.         Study finds no value in heart supplement: CoQ10 not shown to relieve symptoms, UM cardiologist says: https://www.baltimoresun.com/news/bs-xpm-1999-09-27-9909270293-story.html

9.         Secondhand Smoke Ups Heart Disease in Unique Group of Female Nonsmokers – Amish Women: https://www.umms.org/ummc/news/2017/amish-secondhand-smoke

10.       In a First, Man Receives a Heart from a Genetically Altered Pig https://www.nytimes.com/2022/01/10/health/heart-transplant-pig-bennett.html?smtyp=cur&smid=tw-nytimes

Dr. Michael Miller is Chief of Medicine, Corporal Michael J Crescenz VAMC in Philadelphia, PA   Check him out on twitter: @mmillermd1

Natural Foods to Combat Depression During the Holiday Season

While the holiday season is jovial and celebratory for the majority of Americans, it can also be a source of despondency and despair for others. This is especially true for those afflicted with seasonal affective disorder or have great fear and anxiety leading to self-imposed travel restrictions in the midst of the COVID pandemic.

Fortunately, as of this writing, the most recent evidence suggests that if you’ve been vaccinated and “boosted”, the latter should be less of an overriding concern.

Nevertheless, as compared to the pre-COVID pandemic era, levels of depression and anxiety have also risen to unforseen heights.  With the Holiday Season upon us, presented below is a heart healthy selection of foods/drinks proven to enhance mood and combat/limit depression and make your holiday season a more enjoyable one.

1. Mushrooms: A new study of nearly 25,000 men and women found that compared to non-consumers, those who ate mushrooms on a regular basis were less likely to experience signs of depression.  Mushrooms are an excellent source of ergothioneine (ERGO), an amino acid with antioxidant properties shown (in rodent studies) to alleviate symptoms of depression.  Other good food sources of ERGO are beans (black, kidney) and oat bran.
2. Cranberries:  Cranberries are also rich in antioxidants and in the brain protective and anti-inflammatory compound ursolic acid.  Ursolic acid not only reduces growth of certain tumors but has also been shown to improve memory and reduce mood disorders, especially anxiety and depression. Try a handful of cranberries or 4 ounces of pure cranberry juice each day to reap the benefits.
3. Prebiotics: Non-digestible carbohydrate foods (prebiotics) such as garlic, Jerusalem artichokes, leeks and onions, promote the growth of healthy gut bacteria to reduce neuroinflammation and improve symptoms of anxiety and depression.
4. Dark chocolate: A study of ~13,600 adults found that compared to non-consumers, daily consumption of dark chocolate (3.5 ounces) was associated with ~60% lower risk of depression.
5. Coffee: Compared to minimal or no consumption, coffee drinkers have a 25% lower risk of depression. The most favorable results were observed with an average amount of 13.5 ounces consumed daily.
6. Mediterranean Style Diet: A Mediterranean style diet (vegetables, fruits, legumes, nuts, whole grains, fish) is associated with improved mental health in men and women with depression.
7. Kiwi: A recent study found that consuming a kiwifruit daily was associated with improved mood and overall well-being that was attributable to more than the high Vitamin C content.
8. Bivalves: Mussels, oysters, clams and scallops are good/excellent sources of selenium associated with reduced depression and improved mood.
9. Bananas: Bananas are an excellent source of Vitamin B6 with anti-anxiety, antidepressant properties. A banana a day may keep the psychiatrist away!
10. Pumpkin Seeds: Try a small handful of pumpkin seeds daily. The rich content of tryptophan, zinc and magnesium may reduce anxiety and combat depression.

Dr. Michael Miller is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland.  Check him out on twitter: @mmillermd1

Does a High Fat Diet Promote Memory Loss and Cognitive Decline?

A new study out this week and published in iScience found that fat cells play a major role in advancing brain aging and cognitive decline through Na,K+ATPase signaling.  Recent studies have suggested that this pathway is also responsible for conditions that accelerate cardiovascular disease risk including, metabolic syndrome and fatty liver (nonalcoholic steatohepatitis).

The new study was conducted in mice that were genetically modified to release the peptide, NaKtide, in fat cells.  NaKtide is a direct inhibitor of Na,K+ATPase signaling.  The authors found that compared to a control diet, a Western diet (greater than 40% of calories derived from fat) resulted in Na,K+ATPase -mediated cellular inflammation and altered levels of brain biomarkers that affect memory and cognition. These proinflammatory effects were abolished when NaKtide was activated, thereby resulting in improved function of regions that include the brain’s memory center (hippocampus).

The bottom line is that in a mouse model, Na,K+ATPase signaling in fat cells promotes memory loss and neurodegenerative changes.  They raise the possibility that a similarly operative signaling -pathway in humans might lead to adverse long-term neurologic consequences under certain conditions (such as repeated exposure to a high fat diet).  Finally, they suggest that effective therapies directed against this proinflammatory signaling pathway could offset cognitive decline.

Of course, the most effective and currently available approach to reduce cognitive decline as related to this pathway would consist of reducing daily intake of highly saturated, processed and deep-fried foods!

Listed below are additional features related to diet, physical activity, obesity and brain health.

1. Obesity promotes inflammation within the brain leading to cognitive decline and progression of neurodegenerative disorders.
2. Significant and rapid weight loss as a consequence of bariatric surgery has been associated with improvements in cognitive function including memory and executive function.
3. Adherence to the Mediterranean diet – high in vegetables, whole grains, fish, and olive oil – correlates with higher cognitive function.
4. Compared to a high fat, Atkins Diet, a low fat Ornish Diet is associated with low levels of TMAO, a gut metabolite predictive of increased cardiovascular disease risk and reduced cognitive function.
5. Replacement of saturated fat by polyunsaturated or monounsaturated fat is associated with lower rates of neurodegenerative disease.
6. Higher levels of physical activity are associated with a 35% reduced risk of cognitive decline and 14% reduced risk of dementia.
7. A diet containing at least one serving of green leafy vegetables each day is associated with slower age-related cognitive decline by approximately 10 years.
8. Metabolic Syndrome is associated with increased risk of developing cognitive impairment and premature dementia.
9. Chronic exposure to stress confers a higher risk of developing neurodegenerative disorders including Alzheimer’s disease.
10. Chronic insomnia is associated with a 30-35% increased risk of progressive dementia.
11. Musicians are 64% less likely to develop mild cognitive impairment or dementia, even after adjusting for physical activity and education.
12. Drinking 3-5 cups of coffee per day at midlife was associated with a decreased risk of dementia and Alzheimer’s Disease by about 65% at late-life.
13. Speaking at least 2 languages has been shown to delay the onset of dementia by 4-5 years.

Dr. Michael Miller is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland.  Check him out on twitter: @mmillermd1

Let’s Shake on It: Surprising Clues to Heart Disease & Overall Health

Observant physicians can identify important clues about the heart (and overall) health of their patients simply by being attentive to physical appearance and interactions.   While telemedicine has provided an invaluable service during the COVID19 pandemic, many, if not most of us have missed the informative “personal touch”  we have with our patients.

Perhaps the first clue we receive when patients walk through the door is through a simple handshake.  While some of my patients continue to feel more comfortable with a fist/elbow bump greeting since COVID-19, a sizeable proportion have returned to handshakes following vaccination.

As it turns out, grip strength is a strong predictor of cardiovascular and all-cause mortality.

Grip strength can be measured using a hand dynamometer that is relatively inexpensive and readily commercially available. One study found that for each 11% decrease in grip strength, there was a 17% increased risk of death from heart disease. Another study showed that in men and women aged 60 and over, reduced grip strength was also associated with reduced mobility, functional status and cognitive function.

A third study of 500,000 men and women conducted in the United Kingdom also found reduced grip strength to be associated with a 15-30% higher risk of lung and heart disease as well as certain cancers (breast, colon, lung) over the 7 year follow-up period.  Finally, a more recent UK study in 68,000 middle aged men and women (average age, 63.8 years) found greater grip strength to be associated with a diet enriched in omega-3 fats (oily fish such as salmon and sardines) and magnesium (greens, nuts, seeds, whole grains, dark chocolate).

Listed below are several other physical signs that provide important clues when it comes to increased risk of cardiovascular disease.

1. Progressive skin tanning: In the absence of sun exposure, progressive skin tanning may be indicative of acquired hemochromatosis, a condition of iron overload due to excessive intake of iron or multiple blood transfusions.  In this condition tanning may be seen throughout the body, including the face and upper eyelids. Affected individuals should avoid Vitamin C supplementation because of increased iron availability that in turn, may promote disease progression.
2. Bilateral carpel tunnel syndrome:  While carpel tunnel syndrome can occur with repetitive motion/ overuse of a wrist such as from continuous typing/surfing the internet, the development of carpel tunnel syndrome in both hands especially in the absence of repetitive motion/overuse may be due to transthyretin cardiac (hATTR) amyloidosis. This disorder results from the accumulation of abnormal (amyloid) proteins that deposit in various organs and tissues.  Fortunately, treatment is now available for this condition.
3. Blueish Tint of Eye Whites (sclera): In adults, the appearance of blue sclera may be indicative of Ehlers Danlos Syndrome, a connective tissue disorder characterized by joint hypermobility (“double jointed”), skin that is easily stretchable (and susceptible to bruising) and heart involvement (e.g., aortic dilation).
4. Brown discoloration on Neck and Armpits: Also known as Acanthosis Nigricans, dark velvety patches occur in the back of the neck, below the breasts, armpits and groin regions that occur in association with insulin resistance, metabolic syndrome and diabetes.
5. Premature Graying and Baldness: A study of nearly 1400 young men (under age 40) from South Asia found that premature thinning or graying of hair was also associated with a 5-6 fold increased likelihood of premature heart disease.
6. Poor Dentition: A recent study found that spending less than 2 minutes tooth brushing twice daily was associated with a greater than 2-fold increased risk of poor vascular health (as measured by endothelial function).
7. Painful Mouth Sores: Consider Behcet’s disease in someone with a history of recurrent (painful) mouth sores and new onset heart failure.
8. Large Tongue: In addition to amyloid, a large tongue (macroglossia) may be observed with an underactive thyroid (hypothyroidism) especially when accompanied by high levels of (LDL) cholesterol.
9. Split Uvula: A split or bifid uvula is seen in the Loeys-Dietz Syndrome, a disorder affecting connective tissue and associated with aortic enlargement/dissection. The disorder is named after Dr. Bart Loeys and my colleague, Dr. Hal Dietz.
10. Yellowish-Orange Tonsils: Yellowish-orange tonsils is a classic feature of Tangier Disease, a disorder characterized by extremely low levels (e.g., less than 10 mg/dL) of HDL (the good cholesterol).
11. Nodules on the legs: Clues to the diagnosis of sarcoidosis are tender raised reddish bumps (nodules) on the front of the lower legs (Erythema nodosum) combined with heart-related symptoms such as palpitations, dizziness or progressive shortness of breath.
12. Itchy Rash on Chest, Back & Arms:  Very high levels of triglycerides (e.g., greater than 1000 mg/dL) may be associated with a yellowish-red (papular) rash on the chest, back and arms and is often due to poorly controlled diabetes.

Dr. Michael Miller is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland.  Check him out on twitter: @mmillermd1

 

Nutrition & Dietary Approaches to Prevent/Treat Cardiovascular Disease

This past week, I was delighted to receive my copy of “Prevention and Treatment of Cardiovascular Disease: Nutritional and Dietary Approaches” an important new book edited by my colleagues Drs. Michael Wilkinson, Michael Garshick and Pam Taub that focuses on lifestyle strategies for optimizing cardiovascular health.

There are numerous excellent contributions encompassing plant-based, Mediterranean and other popular diets, intermittent fasting/restrictive feeding, dietary recommendations for diabetes, metabolic syndrome, heart failure, atrial fibrillation and many other cardiovascular/inflammatory disorders.

Our contribution entitled, “Lifestyle Approaches to Lowering Triglycerides” was led by Dr. Stephen Hankinson (former University of Maryland medicine resident, currently affiliated with Brigham & Women’s Hospital).

Listed below are some of the numerous “pearls” throughout the book. It is a superb resource for anyone interested in evidence-based medicine as it relates to nutrition and cardiovascular risk reduction.

1. Overwhelmingly, consumption of whole foods enriched in dietary macronutrients have a more pronounced benefit on heart disease risk factors (such as high blood pressure/ cholesterol) than dietary supplements, for whom minimal if any such evidence exists.
2. Inadequate intake of selenium is associated with adverse effects on the cardiovascular system including oxidative stress and inflammation. Excellent sources of selenium include Brazil nuts, oysters and yellowfin tuna.
3. Low levels of magnesium may increase aortic valve calcification (due to buildup of calcium within cardiac and smooth muscle cells). Make sure to include green leafy vegetables, legumes, seeds and whole grains in your diet to maintain healthy magnesium levels.
4. A review of 50 studies evaluating more than 500,000 men and women found that adherence to a Mediterranean diet correlated with a 31% reduced risk of developing the Metabolic Syndrome over a 6-year period.
5. The DASH (Dietary Approaches to Stop Hypertension) is among the most effective non-pharmacologic treatment for high blood pressure with average reductions in systolic pressure (~11 mmHg) and similar to that observed with a single blood pressure medicine.
6. When controlled for total caloric intake, a ketogenic diet does not result in greater weight loss than other diets.
7. In the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, a primary plant based diet (vegetables, fruits, beans, fish) was associated with a 41% lower likelihood of developing heart failure over an approximate 9 year follow-up period.
8. In contrast to popular belief, corn oil has a more profound effect on lowering LDL levels than olive oil (11% vs 4%).
9. A mildly caloric restrictive diet (12% reduction in daily calories) was associated with significant weight loss (average, 16.5 lbs) as well as improvement in cholesterol, blood pressure, insulin sensitivity and inflammation over a 2-year period.
10. Time restrictive eating (6-10 hour window of eating followed by a 14-18 hour fast) reduces risk of cardiometabolic diseases by promoting weight loss and improving sleep.
11. In women with early-stage breast cancer, overnight fasting of 13 (or more) hours was associated with an improved cancer prognosis, longer sleep duration and better glycemic control.
12. In men and women with Metabolic Syndrome, 12-weeks of time restrictive eating (10 hour feeding window) resulted in significant reductions in waist circumference, blood pressure and LDL cholesterol.
13. In more than 1100 men and women with psoriasis, dietary intervention that included a structured exercise program to promote weight loss resulted in a 75% improvement in psoriatic skin lesion severity.
14. In obese men and women with a history of atrial fibrillation, 10% weight loss resulted in a 46% likelihood of sustained normal (sinus) rhythm without medication over ~5 years of follow-up.

Dr. Michael Miller is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland and author of multiple books and book chapters related to heart disease prevention and treatment.