Landmark Results Achieved in Aging and Chronic Disease: Danish Group Extends Disease-free Life by 8 Years

By | July 12, 2019

By WILLIAM H. BESTERMANN JR., MD

New Scientific Breakthroughs Can Provide a Longer Healthier Life

Twenty-one years of follow-up comparing usual care with a protocol-driven team-based intervention in diabetes proved that healthy life in humans can be prolonged by 8 years. These results were achieved at a lower per patient per year cost. Aging researchers have been confident that we will soon be able to prolong healthy life. This landmark study shows this ambitious goal can be achieved now with lifestyle intervention and a few highly effective proven medications. These medications interfere with the core molecular biology that causes chronic disease and aging. These same medications will likely produce similar results in patients with congestive heart failure, chronic kidney disease, arterial disease, history of heart attack, hypertension, and angina. Simple medical interventions can extend healthy lifespan today.

Better Chronic Disease Management Can Improve Health and Lower Costs

90% of health care costs come from chronic diseases and aging which are both related. The same biochemistry that causes aging causes chronic disease. Eating processed food, gaining weight, smoking cigarettes, and sitting on the couch accelerate aging and chronic condition development. Those activities switch on genes that should be quiet. Eating real food, avoiding cigarettes, activity, lisinopril, losartan, atorvastatin, metformin, (and spironolactone) are now proven to extend healthy life by 8 years in patients who are at high risk of health catastrophes and early death! These medications all cost $ 4 a month except for atorvastatin which is $ 9 a month. The benefits continue even when best practice treatment stops probably because these treatments block signaling from dangerous genes that are inappropriately and persistently turned on.

Progress Will Require Extensive Health System Reengineering

Having better health and reducing health care costs can happen today. Surprisingly, the biggest barrier to progress is our current health care system. It is arranged around catastrophes, organ systems, and hospitals. These concepts are 100 years old. Chronic disease begins decades before the catastrophe, and it is related to aging. Age is the greatest risk factor for a heart attack. The same biochemistry that causes accelerated aging also causes heart attack and strokes. It makes little sense to see a cardiologist for a heart attack and a neurologist for a stroke. They are caused by the same molecular biology. The leading health care systems are beginning to recognize that. The interventions that slow aging and chronic diseases development impact every cell in the body. Every young person who is overweight or smokes has activated genes that make accelerated aging and chronic disease more likely. If these genes are switched on prior to having children, that risk is passed on to the next two generations.

Primary care teams organized to address chronic conditions and more rapid aging will provide lifestyle advice and medication that interfere directly with the biology that is causing the problem. The further upstream these individuals are when identified, the easier it is to slow aging and delay chronic disease onset. The path to better health at lower cost lies in the outpatient setting with primary care teams that are well-versed in molecular biology.

Tactics Lag Technology

Medical education and science are in some ways like fundamentalist theology. There is a body of thought that is established dogma and it is very difficult to dislodge. Another way to say it is tactics lag technology. Generals get their soldiers killed by fighting with methods that were appropriate for the last war. It is no different in medicine. There is a 17-year delay between new medical research in its broad application in medical practice. Even then there is substantial variation. Putting stents in patients with stable angina is like marching soldiers shoulder to shoulder into machine gun fire. There are many scientists developing new medications and devices. There are very few working to figure out how to combine the best medical and lifestyle tactics to develop evidence-based care processes consistent with best practices. Perverse financial incentives are also a huge barrier. The winners under the current system that is designed around organ systems, specialists, and big hospital systems are afraid of change that may impact their income, prestige, power, and influence. You can have a longer healthier life, but these barriers must be overcome to make that possible. When that happens, the new system will serve everyone much better and there will be plenty of money to care for those who are less fortunate. Here is an example of the care that we could have.

Prominent Scientists are Working on Extending Healthy Life

Prominent scientists have been working intensely to slow aging and delay disease. They have been optimistic that answers are right around the corner. These leaders met in a 2015 workshop, and concluded: “There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age.” Most of those scientists have been looking for new drugs and similar answers and they have been making progress, but a new study shows that we can have those benefits now.

Healthy Life Extended 8 Years in High-risk Patients in Denmark

A team providing evidence-based care consistent with best practices prolonged healthy life. A Danish group just reported a 21-year follow-up of the randomized, controlled Steno-2 trial which compared usual care with an intensified multifactorial intervention in patients with type 2 diabetes and small amounts of protein in the urine. These patients were chosen because they have a very high risk of heart attacks, strokes, and other expensive diabetic complications. The protocol for the intensive intervention included metformin, atorvastatin, angiotensin converting enzyme (ACE) inhibitors and aspirin. Control targets for blood pressure, LDL cholesterol, and glucose were aggressive. This medical protocol coupled with life style advice produced a “disease-free life extension of 8 years.” At the 13-year mark there was a 4-fold reduction in heart attack, a 5-fold reduction in stroke, a 6-fold reduction in dialysis, a 3-fold reduction in amputation, and a 3-fold reduction in blindness. That is the holy grail. That is not just extending lifespan, that is extending healthspan.

Better Care Is Cheaper Care

Even though aggressively treated patients in this study were healthier longer, their medical care was less expensive. Usual care patients cost €10,091 per year while aggressively treated patients cost €8,725. The overall cost for the two groups was the same, but that was because half the usual care patients were dead at the 13-year mark. The main cost in the aggressive treatment group was brand-name medication. The excellent drugs used during the first 8 years of the trial were very expensive and still under patent. Now these disease-modifying medications are much less expensive and the difference in cost between intensive and usual care should be greater. It is also very likely that the overall results can be improved. New science tells us that spironolactone is another disease-modifying drug that should be added to the protocol. Cutting back on sugar and carbohydrate intake can also make a big difference.

The Same Interventions Produce Dramatic Results in Heart Attack Patients

Heart muscle dies in a heart attack and it is replaced by scar tissue. That injury activates the healing process. Once activated, those genes stay switched on. As a result, scar tissue forms in the entire heart, more heart muscle cells die, the heart becomes larger, and then weaker. It is unable to pump blood adequately and congestive heart failure develops. That whole process becomes a vicious cycle. Without proper treatment, heart failure patients die within five years. ACE inhibitors, angiotensin receptor blockers, spironolactone, metformin, and beta blockers interfere with the molecular signaling that causes progressive deterioration and can even reverse it. High-intensity statin therapy has a beneficial effect. These factors come into play every time a heart attack occurs, and these interventions interfere with the biology that is causing the disease. Our current system is not designed to make sure that every patient gets those interventions every time. As a result, a comparison of intensive management (getting the right $ 4 drug every time) vs usual care (628 patients in each group) showed huge differences. 98 people died of cardiac causes in usual care and 12 in aggressive care. Death from all causes was even more impressive with 188 deaths in usual care and 16 in aggressive care. If these interventions aimed at cardiovascular disease also dramatically reduce all-cause mortality, there are other diseases in play. The right care saved $ 21,900 dollars a year or $ 60 dollars a day. Sixty dollars a day! Just for doing a better job with controlling blood pressure, glucose and cholesterol with the right medication. Just for making sure that every patient gets the right care every time.

Why Does this Approach Work Better?

These interventions work better because they impact central signaling pathways that seem to be involved in aging and all chronic diseases. Rapamycin is the acting ingredient in the more modern drug eluting coronary artery stent. Placing a stent in a coronary artery damages the artery and activates inflammation and scarring. Rapamycin acts on the Target of Rapamycin (TOR) to inhibit stent blockage with scar growth, inflammation, and ongoing atherosclerotic disease. Metformin blocks that same signaling directly. Lisinopril, losartan, atorvastatin and spironolactone block it indirectly. Rapamycin has a local effect in the stent. The other medications impact it in the entire arterial system. Oncologists use rapamycin in cancer treatment. Common gene networks link the causes of cardiovascular diseases and cancer. Rapamycin slows aging in multiple animals. Metformin does the same thing. These disease-modifying medications don’t just impact cardiovascular disease and cancer. They slow progress to blindness and dialysis. TOR is a master metabolic switch that coordinates nutrient supply and growth factor signaling with normal growth in children. It is inappropriately reactivated in later life contributed to cardiometabolic disease development and cancer.

The active ingredient in nitroglycerin is nitric oxide (NO). When a stable angina patient places nitroglycerin under his tongue, nitric oxide quickly moves into the bloodstream and dilates the arteries. That reduces heart work and provides more blood supply. Viagra also provides more available nitric oxide to dilate another important artery. Every one of the disease-modifying agents mentioned in the two studies above increases nitric oxide availability to improve function.

This science and these medical effects show that chronic conditions and aging are related. Taken together, we can begin to talk about a unified hypothesis of chronic disease and aging.

What Would the New Health Care System Look Like?

The new health system would provide access to outpatient primary care services without deductibles or copays. It would provide free access to the proven disease-modifying medications listed above. The demand for facilities can be reduced because blood pressure and sugar can be monitored at home and adjusted over the phone. Care can be more convenient with fewer face to face visits. Protocols, primary care teams, and population health tools are essential. The population health tool helps the team identify patients who have not been seen, have not had a test within the appropriate time frame, are not at goal, or are missing a disease-modifying medication. Without protocols and systems there is no way to know how you produced excellent results and there is certainly no way to standardize and scale it. The new science described here is producing dramatically better results than usual care. It can be standardized, scaled and industrialized. Until someone shows better financial and clinical outcomes, that has to be the standard of care.

We Can Have Better Health Now-But It Isn’t Just Going to Happen

The health care system in the United States could provide better care for all people and save money doing it, but that is not just going to happen. Thousands of people are dying, becoming disabled, and going bankrupt because leaders have not done what they need to do at every level. There has been a roadmap to progress since 2001, but in spite of calls for change, there has been little progress. You need to hold leaders accountable at every level.

Dr. Bestermann is the founder and president of Epigenex Health, Inc that provides a comprehensive solution to improve health and lower cost for patients with cardiometabolic conditions.

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