Healthy Life Extended by Eight Years in a Landmark Study

By: William H. Bestermann, Jr., MD

We know we can extend healthy life using readily available medications and a team-based, systematic approach. But, do we have the will to do it?

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A landmark study from Denmark demonstrated that simple medical interventions can extend healthy lifespan today. It compared usual care for diabetes to care delivered by a protocol-driven team-based intervention. The study had an impressive twenty-one years of follow-up. The results showed that healthy life in humans can be extended by eight years. Further, these results were achieved at a lower per patient per year cost.

Before diving into the details of the study, here is some background.


The investigators already knew that certain types of medications have a greater impact on cardiovascular events compared to other medications that are also able to lower the target risk factor to the same level. These medications include:

  • ACE inhibitors for slowing chronic kidney disease
  • statins for high cholesterol
  • metformin for diabetes

What they wanted to determine in this study was whether a multifactorial intervention with a protocol that included aspirin, smoking cessation and the types of medications described above more effective than usual care? Most doctors at the time believed that risk factor reduction was the critical intervention — not which drug you used to lower it.

Here’s what they did in the study

Patients chosen to participate in the study, called Steno-2, had type 2 diabetes and small amounts of protein in their urine. They all had a very high risk of heart attacks, strokes, and other expensive diabetic complications.

They were randomized to receive either an intensified multifactorial intervention or usual care. The intervention was team-based and consisted of protocol-driven, evidence-based care consistent with best practices.

Medications included metformin, atorvastatin, angiotensin-converting enzyme (ACE) inhibitors, and aspirin. It also included lifestyle advice. Control targets for blood pressure, LDL cholesterol, and glucose were aggressive.

In addition to reducing the level of the targeted risk factor, the medications they used (ACE inhibitors, statins, metformin) all interfere with the molecular biology that elevates the risk factor in the first place. They were getting at the root cause of the problem and not just lowering a number.

At the 13-year follow-up, they found:

  • 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.

At the 21-year follow-up, the researchers found that healthy life in the intervention group patients was extended by eight years.

Can aggressive treatment with the right drugs extend healthy life?

Aging researchers have expressed confidence that we will soon be able to prolong healthy lifespan. In fact, prominent scientists have been working intensely to slow aging and delay the onset of chronic disease. They have been optimistic that answers are right around the corner. Some of these leaders met in a 2015 workshop and reached the following conclusion:

“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, they have been making progress in this arena. However, decades-long Danish study provides strong evidence that we can extend healthy lifespan right now by employing lifestyle interventions and a few highly effective proven medications that we already know about.

Better chronic disease management improves health

Ninety percent of health care costs are related to 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.

The following lifestyle interventions and medications are now proven to extend healthy life.

Most of the prescription medications on the list cost $4 a month except for atorvastatin which is $9 a month.

As I mentioned, these medications interfere with the core molecular biology that causes chronic disease and aging. And, now they have been proven to extend healthy life in patients who are at high risk of health catastrophes and early death. Furthermore, the benefits of these interventions and treatments continue even when best practice treatment stops. This is probably because these treatments block signaling from dangerous genes that are inappropriately and persistently turned on

It is also less expensive

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. 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 at the time very expensive and still under patent.

Now, these disease-modifying medications are much less expensive. So, 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 produced dramatic results in heart attack patients

When heart muscle dies because of a heart attack, 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.

As the heart becomes larger, it becomes weaker. When it is no longer able to pump blood adequately, 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. These interventions interfere with the biology that is causing the disease.

Unfortunately, our current healthcare “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.

Ninety-eight people died of cardiac causes in the usual care group and twelve in the aggressive care group. 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 medications. Just for making sure that every patient gets the right care every time.

TOR and the central signaling pathways

These interventions work better because they impact central signaling pathways that seem to be involved in aging and all chronic diseases. TOR is a master metabolic switch that coordinates nutrient supply and growth factor signaling during normal growth in children. It is inappropriately reactivated in later life contributed to cardiometabolic disease development and cancer.

Rapamycin is the active ingredient in the more modern drug-eluting coronary artery stent. The drug acts on the Target of Rapamycin (TOR) proteins 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 works locally in the stent. However, the other medications impact the pathways throughout the entire arterial system. Of note, oncologists use rapamycin in cancer treatment because common gene networks link the causes of cardiovascular diseases and cancer.

Rapamycin slows aging in multiple animal models. Metformin does the same thing. These disease-modifying medications don’t just impact cardiovascular disease and cancer. They slow progress to blindness and dialysis.

The role of nitric oxide

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.

Extensive health system re-engineering needed to extend healthy life

These studies demonstrate that improving health while reducing health care costs can happen today. Surprisingly, the biggest barrier to progress is our current healthcare 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 healthcare 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.

What would the new health 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. Blood pressure and blood glucose can now easily be monitored at home and medications adjusted over the phone. This will likely reduce the need for care in very expensive facilities, such as hospitals and clinics. Care will be more convenient with fewer face-to-face visits.

Protocols, primary care teams, and population health tools are essential. The population health approaches help the team identify patients, including those who

  • have not been seen
  • are not at goal
  • have not had a test within the appropriate time frame
  • or are missing a disease-modifying medication

Without protocols and systems, there is no way to know if and 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.

The bottom line:

The health care system in the United States could provide better care and produce better health for all people now. And, it could save money doing it.

But let’s be clear, it 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.

We all need to hold leaders accountable at every level.

We need to demand the care that we want and deserve.

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William H. Bestermann Jr., MD is a board-certified internist who practiced preventive cardiology for 20 years. He has been heavily involved with health care reform and quality improvement during that same period. He wrote the first article on a systematic approach to the metabolic syndrome. He led an advanced cardiometabolic medical home that managed high-risk diabetic and hypertensive patients for a Fortune 100 company in Tennessee. He is a Senior Clinical Advisor for the Quality Blue Primary Care program at Blue Cross Blue Shield of Louisiana. That initiative saved $27 pmpm net at the 18 month mark while reducing hospitalizations, length of stay, and specialty referrals. He is currently the Chief Medical Officer at Epigenex Health Inc.

Originally published at on August 12, 2019.

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