Promoting Hunter-Gatherer Fitness in the 21st Century
James H. O’Keefe, MD

Clinical Innovators | Interview by Katlyn Nemani, MD

James H O’Keefe, MD, FACC, is a cardiologist and Medical Director of the Charles and Barbara Duboc Cardio Health & Wellness Center at Saint Luke’s Mid America Heart Institute. He is a Professor of Medicine at the University of Missouri-Kansas City. He has been listed among USA Today’s Most Influential Doctors. In addition to contributing to more than 300 articles of medical literature and authoring best-selling cardiovascular books for health professionals, including The Complete Guide to ECGs, which has become the ECG study guide of choice for American cardiology training programs. Dr. O’Keefe has also co-authored, with his wife Joan O’Keefe, consumer health books including The Forever Young Diet and Lifestyle and Let Me Tell You a Story.

How did you become interested in preventive cardiology? What was your path like to becoming a leader in the field?

By age 15, I had become fascinated with the heart and wanted to be a cardiologist. After completing Internal Medicine and Cardiology at Mayo Clinic, I did a 4th year of CV training as an Interventional Fellow under Dr. Geoffrey Hartzler, the visionary genius who invented primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and who also pioneered multivessel PCI. During my 4th year, Dr. Greg Stone (the other interventional fellow at the Mid America Heart Institute from1988-89) and I scrubbed in with Dr. Hartzler as he labored through diffuse multivessel coronary artery disease (CAD) with nothing but balloon catheters and wires. It was emotionally and physically exhausting work even for our energetic, irrepressible, and controversial mentor.

Patients with stable but extensive CAD flew into Kansas City from all over the world for elective multivessel PCI, and usually developed diffuse restenosis in the ensuing months. It became clear to me that atherosclerosis is a systemic inflammatory disease, and thus its definitive cure would be a proactive preventive strategy not a reactive, invasive, and focal approach. After one long and especially grueling case, Dr. Hartzler looked at me and asked, “Are you sure you want to do this for a living?”

I have the utmost respect for my interventional colleagues and their field is light years beyond where it was 27 years ago. Still, my heart wasn’t in the cath lab; cardiac prevention is my passion. I think we may be entering a new era in cardiology where CAD, except for ACS, is going to be largely managed with conservative noninvasive measures, including the potentially revolutionary PCSK9 inhibitors. The dawning age of U.S. cardiology will be increasingly focused on the rising epidemics of atrial fibrillation, structural heart disease, and heart failure—and prevention will evolve to be important in these arenas as well.

You have promoted exercising “like a hunter-gatherer” to optimize health. What does this pattern of activity look like, and how does it affect gene expression?
Nothing makes an organism flourish like placing it back in the environment for which it’s adapted. Through the marvels of epigenetics, the right types of physical activities can drastically alter gene expression and improve health and wellness. We humans, via natural selection, are the ultimate cross-trainers. I encourage people to mix it up: run, walk, swim, climb, yoga, tai-chi, weight lifting, high-intensity intervals, etc.

Outdoor exercise is particularly exhilarating and relaxing, and it’s great to have an always-eager exercise pal. Humans and canine genes have co-evolved together for tens of thousands of years. We are descendants of dog-lovers, and dogs are designed to be our perfect outdoor exercise companions. Take note, the dog owners and their canine best friends are generally outside exercising regardless of the weather. I often write out a prescription: one dog, taken once or twice daily for a walk or run. Substitution permitted.

Gardening is another ideal exercise for CV health and longevity. An ancient Chinese proverb goes something like this: “If you want to be happy for an hour, have a drink or two. If you want to be happy for a weekend, get married. If you want to be happy for a week, butcher your pig. But if you want to be happy for a lifetime, become a gardener.” Sunshine and fresh air, forager-gatherer style exercise, probiotics from the dirt, and the satisfaction of nurturing life (that doesn’t talk back) is therapeutic. The food and flowers that you grow yourself will improve your health and happiness long before the plants ever, or even if they never, make it to your table. Finally, I also remind people that sexual activity, at the very least, is light-to-moderate exercise, and is a very natural and healthy form of physical activity.

How can we integrate this pattern of activity into our modern-day lifestyles?
I am a huge fan of wearable activity monitors such as FitBit and the new Apple Watch to track things such as steps taken, floors of stairs climbed, sleep quality/quantity. The first step in making effective change is measuring the parameter—when we know better we do better. If you are wearing a fitness monitor, you feel like you ‘get credit’ for your efforts to follow a healthy lifestyle. For example, a fitness tracker will train you so that when you are on the phone you can also be pacing, or stair climbing, or even stepping outside for a stroll during longer calls.

While physical inactivity is well recognized as one of the greatest threats to health in the 21st century, your research has shown that excessive endurance exercise may also cause cardiovascular damage. What are the structural changes involved in “cardiac overuse injury,” and how much exercise is too much?
Overdoing exercise may induce pathological structural remodelling of the heart and large arteries. During extreme endurance efforts such as marathons, ultra-marathons, and long-distance triathlons, the sustained increases in cardiac output, oxidant stress and catecholamines can cause transient stunning and/or micro-injury, particularly in the pliable cardiac chambers as evidenced by elevations of cardiac biomarkers including troponin and BNP. Eventually, this repetitive cycle of micro-injury and repair can lead to patchy myocardial fibrosis, most commonly seen in the atria, right ventricle, and interventricular septum, thus creating a substrate for atrial and ventricular arrhythmias. Additionally, excessive strenuous endurance exercise has been associated with coronary calcification, diastolic dysfunction, and arterial stiffening.

Most long-term studies show a recurring pattern of reverse-J or U-curves whereby light to moderate doses of physical activity, such as walking or jogging, gardening, and leisurely bicycling reduce premature death rates by 30% to 50%; however, partial or complete loss of these benefits are noted with chronic very high doses of exercise. Admittedly, the larger public health issue is that over half of the U.S. adult population is not doing enough physical activity. In contrast, perhaps 2% to 3% of Americans may be overdoing exercise. The cardiac overuse concept is still hypothetical and based largely on observational evidence, but I tell my patients that if they are exercising to improve long-term CV health and longevity, they should aim for moderate instead of extreme efforts, and be sure to take at least 1 day per week off of strenuous exercise.

Your research has shown that vitamin D deficiency may have a direct correlation with cardiovascular disease, diabetes, hypertension, and inflammation. What is the evidence for vitamin D supplementation for cardiovascular risk prevention?
An impressive body of evidence indicates that vitamin D deficiency is an independent risk factor for myocardial infarction, heart failure, stroke, hypertension, inflammation, and diabetes. What we don’t yet know is whether normalizing deficient vitamin D levels will lower these risks. Several large randomized clinical trials that are now underway should help to settle this issue in the coming years. In the meanwhile, I routinely measure serum 25-OH vitamin D levels in my patients with or at risk for CV disease, and supplement deficient levels back into the normal range. Randomized studies have already proven that bringing deficient vitamin D levels back to normal can improve musculoskeletal strength and reduce falls.

You have spoken about coffee and tea as health-promoting additions to an adult diet. What are the cardiovascular benefits? How does coffee affect risk of arrhythmias? 
Coffee and tea, respectively, are first and second richest dietary sources of antioxidants for the average American adult—not only because they are loaded with potent antioxidants, but also because a large proportion of us choose to drink these naturally calorie-free beverages. For the caffeine-naïve, coffee and tea can acutely raise blood pressure and blood sugar and cause palpitations. Yet paradoxically, chronic intake of coffee and tea is associated with lower risks for diabetes, stroke, cardiovascular death, and even atrial fibrillation. As with exercise and alcohol, a U-curve may exist for coffee consumption, whereby moderate intake (2 to 4 cups/day) confers the most robust CV benefits, and excessive consumption may cause problems. Green tea is highest in antioxidant content among various teas, and is a great habit to develop—I make a point of drinking about four to five cups of green tea daily. Indeed, the tendency for caffeine intake to promote physical dependence might even be a plus—daily consumption of coffee and/or tea generally becomes a self-sustaining heart-healthy habit. Coffee and tea are also linked to better brain health, with lower rates of Parkinson’s disease, depression, and possibly even dementia among moderate users. Caffeine can cause sleep problems and anxiety, and takes several hours to metabolize, so it’s best to avoid coffee, in particular, within 6 to 8 hours of bedtime.

While coffee and tea drinking may be easy habits to promote, other dietary and lifestyle changes are sometimes more difficult. Providers often find it difficult to effect behavioral change. What tips do you have for clinicians who are trying to encourage healthy lifestyle changes in their patients?
Admittedly, it is often challenging to find time during our hurried patient encounters to fully address key lifestyle issues such as diet, exercise, stress, alcohol, tobacco and sleep. Still, a strong endorsement by the physician about the patient’s need to invest time and energy in lifestyle issues can make a huge difference. And it really helps if the doctor is setting a good example by ‘walking the talk.’ We refer many of our patients to our Cardio Wellness Clinic to see knowledgeable advanced practice providers and dieticians who follow the patients at least twice a year to provide guidance and feedback. This really helps with patient accountability and improves adherence to the program of diet, exercise, and lifestyle modifications.

Katlyn Nemani, MD, is a physician at New York University

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Sports and Exercise Cardiology, Exercise

Keywords: CardioSource WorldNews, ACC Publications, Primary Prevention, Secondary Prevention, Tertiary Prevention, Exercise, Physical Fitness, Gardening, Holistic Health, Health

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