Can heart disease be reversed?
By Dr Davis
According to conventional medical theory, coronary heart disease is an irreversible, progressive condition. That explains the many thousands of major heart procedures performed every year.
But we're on the dawn of a new age in which reversal of heart disease is rapidly becoming a reality for more and more people. What exactly happens when coronary heart disease is reversed? What does it look like and how do you know when you've achieved it? Is there a scientific rationale behind the Track Your Plaque approach? Here's our Special Report on everything you wanted to know about heart disease reversal.
Coronary heart disease is the cause of death of half of all males, a third of all women. Beyond the toll in human life, it's also the costliest disease in financial terms, far outstripping cancer and other human scourges. Reversal of coronary heart disease—essentially a "cure"—should be the holy grail of medicine.
But you'd never think so, listening to physicians, hospital marketing, or media reports. The focus is the next new stent, defibrillator, robotic surgery, heart transplantation, etc. The whole business of conventional heart care is based on a disease that is unstoppable without procedures. Coronary disease is so relentless that a 10" long chest incision is required. Rarely does a single stent or bypass provide the final solution. Multiple procedures over several years are the rule.
"Modern cardiology has given up on curing heart disease."
Caldwell B. Esselstyn, M.D.
Cleveland Clinic
But if you have a CT heart scan score greater than zero and your coronary arteries thereby contain atherosclerotic plaque, it's natural to ask: Can my plaque be reduced? Can heart disease be reversed?
Studies first hinting that coronary disease regression was possible date as far back as the 1970's. Back then, however, shrinkage was spotty and inconsistent. With treatment approaches available then, rapid progression was much more common, and a modest slowing of plaque growth was regarded as a success.
There's also no shortage of misinformation about heart disease reversal. Enter the search phrase "heart disease reversal" into Google and you'll get over 2 million citations. Countless programs make extravagant claims of "reversing" coronary heart disease with everything from high dose vitamin C, low-fat diets, meditation, to chelation.
How much can you believe? If somebody claims to achieve shrinkage of plaque using treatment X, how can it be proven? How do you really know whether coronary disease is reversed? Does surviving until your next birthday suffice? Does the absence of symptoms mean anything? Does losing 10 lbs tell you whether coronary plaque has shrunk? Should we just follow a treatment program and assume that atherosclerotic plaque has shrunk? How can you know if you have reversed plaque, not just statistical likelihood but actual reversal?
Dr. Ornish had it right—for his time!
The long-time favorite book, Dr. Dean Ornish's Program for Reversal of Heart Disease, was released in 1995. Ornish details a super low-fat (<10% of calories from fat) approach for "reversal" of heart disease. To achieve this extreme level of fat deprivation, meat, eggs, cheese, cooking oil, butter and other full-fat dairy products, and margarine are completely eliminated. Only vegetables, fruits, and whole grains are included.
In 1985, when Americans were indulging in hamburgers, cheese, sausage, French fries, and discovering the joys of fast-food, the Ornish low-fat diet represented an improvement. Eliminate all sources of fats and total and LDL cholesterol drop 30%.
However, as more and more people followed the Ornish program, it became clear that an extreme low-fat diet is also a high-carbohydrate diet. Carbohydrates expand to fill 60–70% of calories to take up the slack left by slashing fat. Most people experience lower healthy HDL and higher triglycerides, both undesirable effects. Hidden patterns like small LDL and VLDL emerge. Many people develop a constellation of abnormalities called the metabolic syndrome, or pre-diabetes (Krauss RM et al 1995). The net effect in many is not reversal, but worsening—more rapid growth of coronary plaque.
How do you know if you've reversed coronary plaque on the Ornish program? Is reducing LDL cholesterol sufficient to know that plaque has shrunk? You won't know. That is the fundamental problem with the Ornish program and others like it. You will not know if you have or have not reversed heart disease. Lowering cholesterol by itself, in fact, is not sufficient to shrink plaque in most people.
The Ornish program was a good solution for its time, just like the 1957 Chevy was a great car for its era. But the time for this program is now long past.
How do we prove that plaque is growing or shrinking?
We know that just feeling good cannot signify whether plaque is growing or shrinking. We also know that indirect measures of risk like cholesterol do not reflect plaque growth. Plaque can grow like wildfire with low cholesterol. Eating healthy and exercise without symptoms? It tells us nothing about plaque growth.
There are several basic requirements for a program for reversing heart disease, i.e., reducing coronary atherosclerotic plaque. They are:
1. We need a method to measure atherosclerotic plaque.
The method should be precise, easy to obtain, and safe. We don't want a measurement tool that is inaccurate, expensive, or dangerous. Intracoronary ultrasound, or ICUS, is an accurate tool for measuring coronary plaque. But it involves invasive methods inserting catheters, a 2–3% risk of heart attack and stroke (because catheters are threaded deeply into arteries), and is costly ($10,000–$15,000). Repeating it every year is an even tougher prospect.
Stress testing won't do because stress tests (stress thallium or other nuclear material, stress echo, etc.) are too crude as measures of plaque. Stress tests are really tests of coronary blood flow. They show abnormalities in the most advanced phases of disease, such that the majority of people at risk for heart attack have normal stress tests. Former President Bill Clinton provides a good example: five stress tests (thallium nuclear tests which were thought to be the "gold standard" for detecting heart disease)) over five years, all normal—until he needed urgent bypass surgery because of severe blockage in all three coronary arteries. In fact, the majority of people destined for future heart attacks have normal stress tests. Stress tests are therefore useless for tracking heart disease reversal.
2. The measurement we choose should reflect the amount of plaque present.
This seems obvious, but in years past, many studies were performed using measuring tools that were poor reflectors of the disease. For instance, researchers used stress tests to gauge whether coronary disease had progressed or not. They reasoned that, if blood flow measured by a stress test improved, then plaque must be shrinking. At first blush, this seems to make sense. Unfortunately, it's not true: blood flow can improve simply because the artery dilates, or enlarges. It tells you nothing about the amount of plaque in the artery wall. Blood pressure medications were initially thought to reverse plaque because they dilated arteries and thereby improved flow, even while plaque grew. Plaque can grow substantially yet not result in any drop in blood flow.
Likewise, images obtained through heart catheterization can appear to show shrinkage of plaque if the artery enlarges. Dozens of studies suggesting 1,2, or 3% plaque shrinkage really proved very little because of artery dilatation.
Another reason both stress tests and catheterization can yield misleading information is because of the "Glagov phenomenon": as plaque grows within an artery, the total diameter of the artery enlarges with it. This means that any test that relies on measuring the internal diameter of the artery, like stress tests and catheterization, can be fooled. Plaque can grow yet not reveal itself by reducing the diameter of the path for blood flow.
The Glagov Phenomenon
There are tests that fit our criteria of safety and accuracy, but don't reflect coronary plaque very well. Ultrasound of the carotid arteries, and ultrasound and ankle-brachial index (blood pressure measurement) in the legs, i.e., tests of arteries outside the heart, do indeed identify risk for heart attack, but are poor measures of actual coronary plaque—they're simply too indirect. One level of plaque in a leg artery, for instance, does not necessarily correlate well with plaque in the coronaries.
There's only one way to accurately and safely measure coronary plaque that meets all our requirements: CT heart scans for coronary calcium scoring. Year to year, they accurately reflect plaque growth or reversal, don't rely on artery diameter measures and are not fooled by the Glagov phenomenon. CT heart scans are also performed with only modest radiation exposure, meet our criterion for safety, and are available at a cost within reach for most people.
What happens when plaque "reverses"
If plaque reverses, it obviously should shrink in size. But what actual changes occur in the plaque?
Most of this information has been obtained from observations in animals, since we are unable to extract plaque from living humans just to assess composition. Among the changes that have been documented include:
* Removal of inflammatory blood cells from within plaque.
* Reduction of lipids (fats) from inflammatory cells within plaque.
* Reduction of the "lipid core", a pool of fatty material that often accumulates within plaque.
* Replacement of fatty tissue with more stable fibrous tissue.
* Reduction of adhesive and inflammatory proteins (Gotto AM 1995).
Recently, further observations have been provided by the tissue-characterizing and precise measurement power of ICUS. ICUS studies have shown that, when plaque shrinks, the overall diameter of the artery is also reduced ("reverse remodeling"), but the lumen (the path for blood to flow) changes very little (Tardif JC et al 2006). In other words, ICUS has revealed that it's not the size of the lumen nor the percent "blockage" that changes significantly, but the volume of atherosclerotic plaque. Plaque volume is therefore what we would like to measure. It's also what is measured using CT heart scans.
A short history of coronary plaque reversal
One of the first observations of atherosclerotic plaque reversal was made nearly 40 years ago by Scandinavian researchers. In their small trial, of 31 patients were treated with niacin, 3 showed reduction of plaque in the leg (femoral) arteries (Ost CR et al 1967). This study went relatively unnoticed for years, though several reports corroborated similar experiences in animals.
Nearly all subsequent studies focused on reducing LDL cholesterol to achieve regression. The first large experience was the Cholesterol-Lowering Atherosclerosis Study (CLAS), conducted by researcher Dr. David Blankenhorn at the University of Southern California, in which the effects of colestipol (an old cholesterol-reducing medication) and niacin on coronary arteries were studied using catheterization (angiograms); LDL was reduced by 43%. 17% of participants achieved slight degrees of "regression" over 4 years of colestipol-niacin treatment (Blankenhorn DH et al 1987).
The CLAS experience triggered a series of similar studies over the next 20 years, all relying on angiograms obtained via catheterization. The majority of studies involved various cholesterol-reducing medications. This list includes the St. Thomas Atherosclerosis Regression Study (STARS) using cholestyramine (an old cholesterol-reducing drug) and a low-fat diet; the Familial Atherosclerosis Treatment Study (FATS) using colestipol and niacin; the Stanford Coronary Risk Intervention Project (SCRIP) using colestipol and niacin along with smoking cessation, weight loss, exercise, and low-fat diet. Like CLAS, these studies all showed "regression" in a few percent of participants, though the majority of participants experienced significant plaque growth (progression) on treatment. The Monitored Atherosclerosis Regression Study (MARS) was the first trial of this design to use then new statin drug, lovastatin (Vigen C et al 2005). Lovastatin, 40 mg per day, along with a low-fat diet, did not achieve overall regression but did achieve less progression: 1.6% progression on lovastatin vs. 2.2% on placebo, though there were more scattered plaques that did regress on lovastatin.
Among the studies that used catheterization was Dr. Dean Ornish's Lifestyle Heart Trial, unique for its time because it used only a very low-fat diet (<10% of calories), exercise, and stress management techniques. This approach achieved an average 2% "regression", compared with 3% progression in the control group not participating in the lifestyle program (Ornish D et al 1990).
But things have changed…
More recently, there has been a trend away from angiograms to measure plaque, since its flaws and limitations have become apparent. A number of studies have been performed using carotid ultrasound measures of plaque. However, these studies have not held up well to deeper scrutiny. Many early studies, for instance, showing carotid plaque regression with treatments like vitamin E, low-fat diet, etc. have crumbled under further study. It could be because carotid ultrasound is an imperfect measure of coronary plaque. Carotid plaque may also be considerably easier to reverse compared to coronary plaque.
Intracoronary ultrasound, or ICUS, has become the gold standard to assess plaque growth or regression. Though it's cumbersome, expensive, carries risk, it can be used effectively in clinical trials involving smaller numbers of patients.
The drugs tested have also become more potent, most notably the cholesterol reducing statin drugs atorvastatin (Lipitor®) and rosuvastatin (Crestor®). The starting doses of these drugs reduce LDL cholesterol more than the maximum doses of the earlier agents, raising hopes for more powerful and consistent plaque reversal.
In 2001, the German Atorvastatin Intravascular Ultrasound Study Investigators (GAIN) reported on an experience with 131 patients, 65 given atorvastatin (Lipitor®) to achieve LDL =100 mg/dl, or placebo. By ICUS, atorvastatin treated patients showed 1.2 mm3 progression of a selected area of plaque, compared to 9.6 mm3 without atorvastatin (Schartl M et al 2001).
An interesting experience was reported by another German group using ICUS of the left mainstem coronary artery (the shared stem of the left anterior descending and the circumflex arteries). Over 18 months of treatment with statin drugs, participants who achieved LDL cholesterol =75 mg/dl showed no progression of plaque, while those with LDL =120 mg/dl showed the most plaque growth (von Birgelen et al 2003). In addition, participants with HDL cholesterol values of 60 mg/dl were more likely to experience no plaque growth, and HDL>60 mg/dl tended to be associated with regression.
The efforts of Cleveland Clinic cardiologist, Dr. Steve Nissen, have yielded several recent studies that shed additional light on plaque reversal. The Reversal Study compared high-potency statin treatment (Lipitor®, 80 mg; LDL reduced to 79 mg/dl), to a low-potency treatment (Pravachol®, 40 mg; LDL reduced to 110 mg/dl), High-potency treatment shrunk plaque a modest 1%; low-potency treatment, on the other hand, allowed plaque growth (Nissen SE et al 2004). A similar study, the Asteroid Trial, demonstrated 7% reduction in plaque volume after two years of Crestor®, 40 mg per day, which resulted in LDL cholesterol of 61mg/dl and HDL of 49 mg/dl (Nissen SE et al 2006).
Unfortunately, the high doses of atorvastatin and rosuvastatin used in these recent studies are very poorly tolerated in real life, with most people developing intolerable muscle aches and weakness within a few weeks or months of starting. We also remain highly skeptical that a strategy focused solely on reducing LDL is sufficient to reverse coronary plaque in most people. In fact, in our experience, reducing LDL to =60 mg/dl is an important factor, but it rarely is the only factor that results in completely halting plaque growth. Nonetheless, these experiences have opened the door for more research into the question of atherosclerotic plaque reversal and add to our overall understanding of the phenomenon.
Beyond LDL cholesterol…
Have strategies beyond LDL cholesterol reduction achieved plaque reversal? The above experiences have proven that, while reduction of LDL may achieve regression, it does so incompletely and inconsistently. Are there strategies for treatment beyond LDL cholesterol that may provide more powerful strategies? Unfortunately, this area is not as well sorted out as LDL reduction.
Most of the studies discussed above that focused on LDL cholesterol also showed that, while the treatments used did not increase HDL more than a few points, the more HDL was raised, the more likely regression developed. This has been supported, though with carotid ultrasound, by the 1,952 participant Tromso Study, in which people with higher HDL cholesterol experienced less plaque growth than those with low HDLs (Johnsen SH et al 2005). For this reason, raising HDL has been explored as another strategy to regress plaque. HDL may, in fact, be the factor that is largely responsible for many of the phenomena that are required to reduce plaque.
One study worth special note is the HATS Study, in which simvastatin (Zocor®), 40 mg, was combined with niacin. The HATS Study was the first to combine a statin drug with niacin. Patients treated with the combination experienced 0.4% plaque regression; participants taking placebo experienced 3.6% progression over three years (Brown G 2001). In addition, 24% of placebo participants experienced heart attack or other events, compared to 3% in the simvastatin/niacin group—a remarkable near total elimination of events over the three year period.
The ARBITER Study showed that niacin, 1000 mg, added to statin therapy halted carotid plaque growth completely (though not in all participants), compared to statin therapy without niacin (Taylor AJ 2004). This was achieved with an HDL of 47 mg/dl.
Another study that adds support to HDL's role in plaque regression was a study in which an experimental intravenous infusion of an HDL-related protein, ApoA1 Milano, was administered. The preparation was given to patients who experienced a recent heart attack. Images of a selected coronary artery region were obtained with ICUS before treatment and then again after five intravenous treatments over five weeks. Participants who received ApoA1 Milano regressed 5.4%, while participants receiving placebo regressed only 1.7%. With only 41 participants, this study is small and needs to be validated in a larger trial which is underway (Nissen SE et al 2003). (For more on ApoA1 Milano, see the Track Your Plaque Special Report ApoA-1 Milano: Hope for a Cure or Hype for Profit?) Unfortunately, this agent will likely be limited in usefulness by its intravenous administration and high cost (since it's a product of recombinant gene technology).
Fish oil's great usefulness is to reduce triglyceride-rich lipoproteins that cause coronary plaque like VLDL and IDL, postprandial (after eating) lipoproteins, and to stabilize plaque structure by inserting omega-3 fatty acids into plaque. In the MARS and CLAS trials (above), triglyceride-rich lipoproteins were associated with plaque growth. Fish oil may therefore be expected to exert plaque-reducing benefits, as well. A German catheterization study in 223 participants showed modestly greater regression in those taking fish oil for 21 months compared to placebo (von Schacky et al 1999). More impressive was the reduction in heart attack and death in those taking fish oil, similar to that observed in the much larger GISSI-Prevenzione Trial. Fish oil is, therefore, not terribly powerful for regression by itself, but more useful as an adjunct to a broader effort of plaque reversal.
The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was a European trial that used the fibrate drug, bezafibrate (unavailable in the U.S.) which, like fish oil, reduces triglyceride-containing lipoproteins (triglycerides reduced 46%; VLDL reduced 53%. This trial also used catheterization to compare participants on the drug or placebo; those taking bezafibrate showed significantly less progression (Ruotolo G et al 1998). Similar observations have been made with the related drug, gemfibrozil (Lopid®) (Karpe F et al 2001).
Lessons we can learn
The clinical trial experience is insufficiently developed to advise us precisely how to reduce coronary plaque. No one strategy emerges from trials that guarantees plaque reversal. The degree of plaque reversal reported in clinical trials is also rather modest, usually amounting to a few percent. Total reversal remains elusive. One weakness of most of the trials is that they explore the power of a single treatment strategy, e.g., a statin drug.
Combination therapy appears to hold greater promise. The most powerful evidence of regression comes from experiences like the HATS Trial, in which a statin drug was combined with niacin. Combination treatment has been the most powerful for both reversing plaque as well as dramatically reducing "events" like heart attack (85–90% reduction).
How the Track Your Plaque program fits in
Track Your Plaque takes the lessons learned from previous efforts and combines the most powerful strategies together in a program that heavily stacks the odds in favor of achieving heart disease reversal.
First, we use CT heart scan technology to quantify plaque. CT heart scanning offers a combination of precision, safety, and cost-effectiveness unmatched by any other procedure or technology. Keep in mind that each person responds differently and uniquely to each heart disease reversal strategy. Without the capability to precisely measure plaque growth and regression, it would be practically impossible to evaluate the effectiveness of multi-regimen therapies and make the any needed changes, updates, or additions.
Second, all causes of coronary plaque need to be identified. The Track Your Plaque program relies on new breakthroughs in lipoprotein analysis to uncover previously hidden causes of plaque growth. If hidden causes remain unknown and therefore uncorrected, plaque growth will continue. On the other hand, if as many causes as possible are identified and corrected, then you've got the best possible chance of reversing plaque.
Third, all abnormalities are treated and corrected. Since no single medication, supplement, or lifestyle change corrects all contributors to plaque, a combination treatment program is nearly always necessary. Thus, the crucial components of the Track Your Plaque strategy for plaque reversal and slowing, halting, or reversing your heart scan score includes (but may not be limited to):
* Reduction of LDL to 60 mg/dl
* Reduction of triglycerides to 60 mg/dl
* Raising HDL to 60 mg/dl
* Correction of hidden causes like small LDL, IDL, Lp(a), and others.
* Achieving normal blood pressure (<130/80)
* Achieving normal blood sugar (=100 mg/dl)
* Reduction of C-reactive protein to <1 mg/l
* Addition of fish oil
* Normalization of vitamin D blood levels
This approach is not 100% successful. But it is, by far, the best and most powerful approach available to us with present day knowledge. While it can't guarantee success in reversal, it tips the scales heavily in your favor. We are currently witnessing 10–30% reductions in heart scan scores commonly in our participants in the first year. We're also actively investigating all new strategies that may promise to increase our success even further.
Coronary plaque shows as a
white area on a CT Heart Scan
Note reduction in area (18%) after one
year on the Track Your Plaque Program
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