Homocysteine and Folic Acid Supplementation: Another Medical “About Face”

On March 15, 2015 JAMA published on line the results of a superbly designed and potentially practice changing trial. The China Stroke Primary Prevention Trial (CSPPT), tested whether or not the addition of folic acid to anti-hypertension medication could reduce the occurrence of a first stroke. As three quarters of all strokes are “first strokes” and as strokes are a leading cause of death and disability worldwide, the question posed by this trial had far reaching implications. The trial met its endpoint so quickly and incontrovertibly that for ethical reasons it was prematurely terminated. Folic acid can reduce the risk of stroke. Those of us who have open-mindedly interpreted prior studies expected this finding; many others found the results to be shocking.

Important homocysteine related trials like HOPE 2 and others had already demonstrated either statistically significant reductions in stroke with folic acid supplementation or at least signals toward such an outcome. Yet many of the most “vocal” researchers, physicians, and reporters proclaimed that since heart attacks were not reduced with folic acid, “the homocysteine hypothesis was dead.” This perspective always bothered me. We had observational and even interventional trial data supporting the use of folic acid in certain settings. And stroke, the disorder we could impact with a simple vitamin, is horrific. Strokes are terrifying, disabling, and deadly. They are also extraordinarily common. So why would these doctors, scientists, and media members snub data supporting a simple and safe vitamin treatment to potentially reduce such events? It would be helpful to know the reason, as the same phenomenon is currently occurring in relation to omega-3 fish oils.

Plenty of data support fish oil supplementation yet a few trials do not. And as with homocysteine, it seems that the media and many scientists/doctors have chosen to focus their attention on the limited neutral – and oftentimes overtly flawed – data rather than supportive experimental, biologic, physiologic, clinical trial, and common sense evidence. Interestingly, one of the vital lessons gleaned from CSPPT is that those individuals with either specific genetic mutations or very low levels of folic acid received the greatest benefit (reduction of stroke) from taking folic acid. In parallel fashion, one of the key trial limitations of fish oil studies has been the persistent failure to measure blood levels of the omega-3 fatty acids DHA and EPA. It certainly stands to reason that those with lower levels of these critical fats will also gain the greatest advantage from their supplementation. So why not simply measure them? Well, in clinical practice, some of us do. And some of us even advise correcting abnormally low levels with simple and safe fish and fish oil pill consumption.

I am at once elated and disturbed by the CSPPT findings. They prove the efficacy of a simple therapy; yet, they broadcast the hubris of many in my field. Time and again we have had to make an about face in our opinions and recommendations. I see nothing inherently wrong in changing our position as more data emerge. What I struggle with is the egg on our face, the about face that occurs far too late, long after adequate data have told us what to do. Perhaps we will learn though. Maybe as more trials like CSPPT emerge, as more scientists and doctors with the conviction and devotion to finding a greater truth push tirelessly along their paths we will finally learn to be more open minded and accepting of ideas and findings even when they go against our grain.

For more information about the supplements and vitamins critical to your everyday health visit www.vitalremedymd.com.

Learn more about preventive cardiology at www.preventivecardiologyinc.com.

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Our “Guardian Genes”: The Modern Doctor’s Holy Grail

Any doctor worth his salt recognizes that patients don’t always respond the way we anticipate they will. For example, utilizing the best of our scientific methodologies we know LDL is causally related to vascular disease. High LDL causes disease while low LDL mitigates it.  Yet, we occasionally see patients with extraordinarily high LDL and no disease, as well as those with very low LDL and severe disease. In some circumstances, patients with a vascular disease promoting mutation – as in Familial Hypercholesterolemia – will have severe and premature heart disease while their relatives with the same mutation somehow remain unscathed. How can this be? What we’ve all come to believe is that there must be protective genes that somehow offset the detrimental aspects of other genes. Let’s dub these desired genes “Guardian Genes”.

In the case of vascular disease promoting disorders, Guardian genes cause the exception, not the rule. They Teflon coat individuals who under normal circumstances should develop heart attacks and strokes. This wonderful rarity can unfortunately lead to a misunderstanding of disease processes as well as their cures. When someone speaks of grandma whose LDL was 300 and yet lived to the ripe old age of 100, sans MI or stroke, the take-home message often is, “Those doctors don’t know what they’re talking about. LDL is not the cause of heart disease. My LDL is only 200 and as grandma lived to 100 and with worse numbers, why should I take that statin medicine. Just look at the Internet and you can see how terrible those medicines are.” Unfortunately the Guardian genes are currently merely speculative. As such we cannot identify them. And, we know that intra-family variability in development of vascular disease supports the notion that theses guardian genes are inherited entirely separately from the disease promoting genes. What that means is just because grandma won the lottery, don’t bet your life (literally) that you did as well. In my own practice I’ve seen 70-year-old parents mourn the deaths of their 40-year-old sons and daughters who died of MIs. Though they shared the same bad genes, the parents did not suffer the unfortunate (and more predictable fate) of their children.

The bottom line here is that we doctors must base our treatment recommendations on the odds. We weigh and measure the pros and cons of therapeutic options (like the statins) against the likelihood that an individual patient will develop a serious event such as a heart attack, stroke, or even death. We use our best judgment based upon many facets of knowledge and understanding. We then make our recommendations hoping to stave off future adverse cardiovascular events. We never risk a patient’s life hoping he or she has inherited a guardian gene. Until we identify the elusive lifesaver guardian genes they will remain relegated to being the modern day Holy Grail of genetics. We all pray we will find them, but until that day we must continue to practice within the limits of our understanding. And while we do, we hope our patients understand that our suggestions and recommendations are born of both a deep understanding of the science of medicine and the burning desire to help our patients live the longest and best lives possible.

Learn more about preventive cardiology at www.preventivecardiologyinc.com.

For more information more about essential vitamins and supplements visit www.vitalremedymd.com.

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The Approaching Medical Maelstrom

The AHA 2014 Scientific Sessions are over and I have already written twice about IMPROVE IT but I feel compelled to write again. Although the media has been oddly silent about the trial (why is that I wonder???), I predict its fallout will greatly impact the disciplines of Cardiovascular Disease Prevention, Clinical Lipidology, and even the essence of clinical practice. The reasons are manifold. First, the trial proved two critical theories: a lower LDL cholesterol level is better, and statins are not the only way to achieve a clinically relevant LDL reduction. Additional key considerations from IMPROVE IT include:

  •  Lower LDL in properly chosen patients (and probably almost everyone) yields lower rates of stroke and heart attack, the two most formidable foes of modern man. For example, in the trial, an LDL of 53 was significantly better than an LDL of 70. Should we doctors then aim for 40, or perhaps even 25?
  • In our high-risk patients should we consistently and continuously add medications to statins in order to drive cholesterol levels lower and lower? For example, in a patient with a prior heart attack is it now fair to accept 70 for an LDL when we know that 53 would decrease our patient’s chance of having a recurrent and potentially life-threatening event?
  • What do we do with the hotly debated 2013 ACC/AHA Cholesterol Guidelines? They eliminated LDL goals and allowed for the use of Zetia only with individualized – and typically time-prohibitive – clinician/patient discourse, but they did NOT encourage driving LDL lower than 70. The Guidelines advocated for an LDL response to therapy of > 50%. So where does that leave our heart patients who start with LDLs of 180, for example. If they achieve the intended LDL reduction of 50% and thereby remain with an LDL of 90 mg/dL the guidelines surely say all is well – job well done. They state there is no indication to go further. Well now there is an indication. Now we can say with certainty that an LDL of 53 is a far better goal than 90. Having an LDL of 90 leaves significant and now manageable residual risk. So then how can a health care provider in good conscience advocate keeping such a patient at an LDL that clearly conveys greater risk?
  • The Guidelines also strongly advocate our utilization of maximum statin doses prior to adding an agent like Zetia. Knowing that higher dose statins produce more side effects while yielding a diminishing return on cholesterol lowering, wouldn’t it now be more prudent for doctors to prescribe low dose statins in combination with Zetia? This would limit side effects while yielding lower LDL levels than would the Guideline recommended approach. More food for thought.
  • How will insurance providers respond to Improve-It’s results? After the ACC/AHA Guidelines’ release, with lightening speed they downgraded access to add-on therapies such as Zetia. Of course that saved them money. So what now? Will they respond in kind, follow the science, and quickly allow patients access to these medications? We shall see but I have my doubts. Profits it seems oftentimes take precedence over science and health.
  • One more crack at the Guidelines for now: It is true that we do not know what represents the optimal LDL cholesterol level in human beings. Based upon our ever-expanding understanding of lipids including our body’s limited need for extraneous cholesterol however, it is safe to say that that level is probably quite low, perhaps even as low as 25 or 30 mg/dL. And, given the fact that many of us are goal-oriented, wouldn’t it now make sense to join our friends across the pond as well as our very learned friends here at home in the National Lipid Association and simply reinstate LDL goals?
  • As I sit at my desk tapping these keys I am clearly frustrated by the politics and economics woven inextricably into the fabric of medical practice. But I am also comforted and encouraged by the knowledge that many of us have already spent the last decade and beyond practicing the way we felt the science dictated. And by so doing, in the matter of LDL-lowering with Zetia, for every 120 patients we’ve treated in an Improve-It style, we’ve saved 3 from enduring a stroke or heart attack. This fact renders all our struggles worthwhile.

On a final note let us not forget that doctors have NO financial incentive to prescribe these medications. Our only “dog in the fight” is protecting our patients from harm. Insurance providers often do have a financial incentive to preclude doctors from prescribing some medicines (typically those that cost them more money). So whom do you, the patients, want to be in control of your medication regimen – the more highly educated and clearly non-conflicted physicians, or the less knowledgeable and often-conflicted insurance carriers? The answer to me seems pretty clear.

Learn more about preventive cardiology at www.preventivecardiologyinc.com.

For more information more about essential vitamins and supplements visit www.vitalremedymd.com.

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The Glory of Gum – A Smoker’s Tale

Recently, on a medical sojourn, I was met at the airport by a garrulous woman driver. She was a young-appearing fifty year old who as it turns out had recently sustained a TIA, or “mini-stroke.” Although my first thought was atrial fibrillation, she actually had developed a near occlusion of her left carotid artery. Her right carotid artery, she informed me, had a mere 40% stenosis. Our discussion continued and I gleaned that she had a very strong family history of early onset vascular disease, several close relatives even dying quite young from their events. So my next thought was Familial Hypercholesterolemia. But no, her LDL was apparently normal. Then she fessed up. She had been – and continued to be – a smoker. Just like everyone else in her family! Shocking.

To smoke cigarettes nowadays is something I simply cannot wrap my head around. Cancer, stroke, heart disease, lung disease, wrinkles… Tobacco is devoid of any redeeming quality. It’s just plain bad. So why would anyone smoke in the first place? But, once an individual has experienced a near death event that is a direct consequence of tobacco, how in the world could she continue to smoke. My 40-minute drive took on a mission. I was going to get her to quit. I asked about her children and even grandchildren. We spoke about loss of limbs, dependence upon an oxygen tank, facial cancers and their attendant disfigurement, another stroke – the next one of course placing her in a wheel chair, unable to speak or care for herself. Then she dropped me at my destination. She was to pick me up several hours later. Before stepping out of the car I told her with stern authority that a cigarette should never again cross her lips. Chew gum I said. Gain weight if you must, but please don’t ever come near another cigarette. (I must confess; my tone was intentionally severe and perhaps even paternal. The impact I hoped would justify my behavior.)

I went through my day, completed my tasks, and eagerly awaited her return. Upon her arrival she stepped from the car and proudly and loudly through a mouthful of gum intoned that she had done it. She quit smoking. I am not certain whether her resolution will last an hour or a lifetime. For that moment though she was no longer a smoker. A gum chewer yes, but not a smoker.

Learn more about preventive cardiology at www.preventivecardiologyinc.com.

For more information more about essential vitamins and supplements visit www.vitalremedymd.com.

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Familial Hypercholesterolemia – a Common Yet Life-Threatening Genetic Disorder

This article was originally published on HomeCareforYou.com.

You or someone you love might be harboring an undetected threat called Familial Hypercholesterolemia (FH). As genetic disorders go, FH is quite common. In fact, the condition occurs five times as frequently as Cystic Fibrosis. FH victims typically have severely elevated cholesterol; their disorder frequently remains undetected; and most patients develop vascular disease very early in life. These people often die from heart attacks in their forties and fifties. One consequence of the explosion in our understanding of genetics has been the discovery of more than 1600 genetic mishaps that can lead to FH. In the general population this disorder occurs in one out of every 500 people. Specific populations called founder groups (groups of people who are descendants of a genetically similar small population) such as French Canadians, Christian Lebanese, and South African Ashkenazi Jews have a prevalence of this malady that can be as high as one in sixty-seven people.

So what is FH and how does it harm so many?
cholesterol meterIn order to understand this ailment we must first review a few basic elements regarding cholesterol and its main transporter, LDL (Low Density Lipoprotein). Cholesterol is the building block for many key components in our body. LDL is a spherical lipoprotein particle that carries cholesterol. Think of it as a floating bubble that carries its freight— cholesterol and triglycerides—from one part of our body to another. This LDL “bubble” serves as a barrier “protecting” us from what would otherwise be the consequence of cholesterol floating freely in the blood. The result of that scenario would be instant death; free cholesterol would form razor-sharp crystals shredding anything in its path. LDL particles obviously provide a valuable function as our body’s dominant cholesterol transporters, but they have been dubbed the “bad cholesterol” because overly-abundant levels of these lipoproteins clearly lead to heart attacks and strokes. Thousands of studies have proved this; it is one of the few “facts” we have in modern medicine. As a result of our understanding of the detrimental consequences of high LDL, medications such as the statins have been created to lower LDL levels and in turn diminish our chances of experiencing a heart attack or stroke.

Lowering LDL with statins
Most of us know that the fundamental medication in cholesterol management is the statin. Statins work by blocking a critical enzyme in the multi-stepped process of cholesterol synthesis. This enzyme is present in every cell in the body. In response to the statin-induced cholesterol decline within our cells, affected cells deliver a greater number of LDL receptors to their surface. Think of receptors as adhesive-coated indentations in the cell membrane. These receptors capture the LDL “bubbles” as they float by in the blood. The receptor with its bonded LDL particle is then brought inside the cell. Within the cell, the cholesterol contained within the LDL particle can be utilized in any way the cell deems fit. For instance, it can be a building block for Vitamin D in the skin, bile acids in the liver, or testosterone in the testes. Once a cell has acquired enough cholesterol to serve its manufacturing needs, it stops overproducing LDL receptors. All cells engage in this process, but our liver is the organ that manufactures the majority of LDL receptors, thereby most meaningfully diminishing the content of LDL within our blood. To maintain a healthy balance of LDL within our bodies it is essential for our cells – particularly within our liver – to be able to produce LDL receptors, position them on their surface, and capture their prey—LDL particles.

The Malady of FH
Patients with Familial Hypercholesterolemia possess a genetic defect that disrupts their LDL receptors. In some cases the patient manufactures too few receptors; in others, the receptors themselves are defective. Even though they capture LDL, faulty receptors are unable to successfully bring their cargo into the cell. This defect results in a situation wherein the cell “effectively” lacks LDL receptors. There are two types of FH patients, those who have inherited one faulty gene from one parent (the common variety – 1 in 500) and those who have inherited one faulty gene from both parents (the extraordinarily rare form – 1 in 1,000,000). When an individual receives an abnormal gene from only one parent, he or she is known as heterozygous for the particular genetic flaw involved. An individual is homozygous for a disorder when both parents contribute abnormal genes. Because of the nature of the FH genetic defect, heterozygous individuals–those possessing only one genetic error from one parent–will experience the disorder, albeit in a less aggressive form than their homozygous counterparts. As this defect causes suboptimal LDL receptors, patients develop extraordinarily high LDL cholesterol levels. A typical heterozygous patient will have LDL cholesterol in the 200s. Homozygotes have LDL cholesterols over 500! So here is the problem. From conception on, FH patients’ bodies are bombarded with excess LDL cholesterol. Their arteries, tendons, eyes… everything is soaked in cholesterol. In contrast to patients who do not have this disorder, afflicted individuals have a markedly prolonged burden of high LDL. They bathe in cholesterol their entire life. That is why these individuals develop premature cardiovascular disease. In fact, patients with FH have a 12-fold higher risk of coronary artery disease compared with their own unaffected relatives. FH patients have a fifty percent mortality by the age of sixty if they are inadequately treated. And even more frightening, FH patients typically live their lives in the dark, undiagnosed and untreated. With- out being properly recognized, appropriate and life-saving care cannot possibly be rendered. Thus, our charge is crystal clear: Doctors must improve our ability to identify these patients early on in life and by so doing treat them appropriately and diminish their risk of dying young.

The FH patient
Let’s truly “look at” the patient with FH. In order to be able to recognize and appropriately treat these individuals, doctors and patients must be familiar with what this disorder looks like. First it’s critical to know that LDL cholesterol levels fluctuate throughout our lifetimes. We are born with our lowest levels, and after puberty LDL steadily rises throughout the rest of our lives. So pediatricians must appreciate that an LDL cholesterol of 160 might indicate the presence of FH, whereas in an adult this same LDL cholesterol level would be considered only moderately elevated. It is also important to understand that men and women have very different cholesterol levels. Until menopause, women have lower total cholesterol, LDL cholesterol, and triglyceride levels; and higher HDL cholesterol levels than men. Unfortunately, after menopause each of their lipid parameters deteriorates. Thus, physicians need to have a solid grasp of the influence that gender and age have on all lipid values (my lecture on this can be found at (http://aspconline.org/resources/ highlights.php). You can see that there is often great complexity in interpreting lipid and lipoprotein values; it is therefore important at times for patients to see lipid specialists in order to receive more refined therapy (To find a lipid specialist near you, visit www.lipid.org). We know what FH patients’ lipids look like, and we know that their vascular tree is severely diseased by an overabundance of LDL, but what other manifestations result from such high lifetime LDL levels? In addition to vascular disease, there are also disfiguring non-arterial consequences of FH. A life-time of markedly elevated LDL cholesterol can lead to an accumulation of fat in unusual parts of our bodies. Our tendons are often affected where fatty deposition can lead to palpable lumps called xanthomas. The Achilles tendon is a frequent target of this aberrant fat accumulation. Tendon xanthomas can easily be seen by the naked eye. Our palms can also be affected, with an abnormal yellowish discoloration in their creases called palmar xanthomas. Another area for physicians to focus their attention is our eyes. In the corner of the eye, adjacent to the nose, we can at times see yellowish deposits called xanthelasmas. In the eye itself, we sometimes see light-toned fatty deposits called corneal arcus. These tend to occur on the bottom and top of the cornea at the edge of the iris (the-colored part of the eye) because that is where the density of blood vessels is greatest. Seeing tendon and palmar xanthomas, or corneal arcus in patients under the age of forty-five, essentially confirms the diagnosis of FH.

Treatment Options
In 2011, initiating an FH call to action, the National Lipid Association released guide- lines to improve the identification and treatment of these patients. The NLA guidelines emphasize early detection; we now know that under appropriate circumstances very young children (even two years old in some cases!) should be screened. Once a patient has been diagnosed with FH, it is important not to stop there, but to perform “cascade” testing. This is a rigorous search of the patient’s relatives to determine who among them might also have the disease. Through proper cascade testing, doctors can discover many additional patients who would otherwise have been left untreated. Along with the National Lipid Association, other organizations such as the American Society for Preventive Cardiology and The FH Foundation are doing their part to raise FH awareness. Pharmaceuti- cal companies such as Genzyme and Aegerion are also help- ing out. Pharmaceutical companies frequently sponsor scientific educational conferences, enabling doctors to remain current with the ever-changing landscape of medical knowledge. They build websites devoted strictly to educating the lay public, allowing all people to more effectively become their own advocates. And of course they also create the medications, such as statins, that lower our risk of heart attack and stroke. In the case of FH, Gen- zyme has fashioned a novel medication, Mipomerson, in order to more effectively manage patients with extraordinarily high LDL levels. Aegerion has created Lomitapide another unique LDL-lowering agent. Other innovative agents are in the works. Those of us who specialize in the management of severe lipid disorders are thrilled to have access to ground-breaking medications that will hopefully make an even greater dent in the damage inflicted by FH. Finally, let’s examine the state-of-the-art management of FH individuals.

First and foremost, diet and exercise are always paramount in maintaining optimal cardiovascular health. For FH patients though, more aggressive treatment is always needed. To “get them to goal”, combination therapy is uniformly required, which means using a statin as the foundation and then adding two, three, or even four other medications. Novel agents such as Lomitapide (Aegerion) and Mipomerson (Genzyme) were recently FDA-approved for the treatment of severely afflicted FH patients. These medications represent a new and welcome addition to Lipidologists’ medical armamentarium. Even still, many of these patients require more aggressive interventions. One of the best modalities available is LDL-Apheresis. In a manner similar to dialysis (minus the fatigue and potential side-effects), patients are connected to a filtering machine through two IV lines. Blood is withdrawn from one IV, circulated through a series of filters, and returned to the body through the other IV. Typically the two-hour procedure is performed in an outpatient- setting once every other week. Each treatment results in a 60 percent to 80 percent reduction in LDL (other pro-atherogenic substances are also removed). Over the ensuing two weeks, the LDL rises steadily until it can be lowered once again with another treatment. Despite the fact that LDL gradually increases between treatments, studies have demonstrated a nearly 75 percent reduction in cardiovascular events when patients are treated with LDL-Apheresis. Thus, LDL-Apheresis is a viable option for difficult-to-treat heterozygotes and mandatory for all homozygotes. (To find a center near you, visit www.lipid. org) Familial Hypercholesterolemia is a frequently undiagnosed genetic disorder adversely affecting patients’ lipids and leading to premature heart attack, stroke, and death. A solid understanding of age and gender associated lipid fluctuations, physical signs of FH, and the nuances of cholesterol management is essential for doctors to diagnose and treat this disease. Somewhere between 600,000 and one million Americans suffer from FH. Consequently we must do our best to understand, manage, and perhaps most important of all, “spread the word” about this insidious but conquerable threat. It is a mission that can be accomplished only through the coordinated efforts of doctors, scientists, medical associations, industry, and patients themselves. Fortunately, this is what we find taking place today.

Please read more about preventive cardiology at www.preventivecardiologyinc.com.

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Freedom through the Eyes of a Preventive Cardiologist

As an Interventional Cardiologist turned Preventive Cardiologist I understand all too well how much better it is to prevent a disease before it ever has the opportunity to strike. After all, what would you rather experience – a heart attack, angioplasty, stroke, or bypass surgery – or simply a modification of your lifestyle – eating better, exercising regularly and perhaps taking a medicine or two? Most of us would opt for the latter. I’ve yet to meet anyone who has enjoyed the experience of a major cardiac event, but most everyone likes being lean, fit, and energetic. Recently I was struck by the application of “prevention” to politics.

Americans are in the throes of controversy regarding freedom. Daily I listen to my patients as they express their worries that we might be on the road to socialism. Most people would reject such a notion, saying, “it’s impossible; America will always be the land of the free.” Yet, the patients who fret the most are those who actually lived through times of dramatic social change – Cubans, concentration camp survivors, former Eastern Europeans… These individuals have had the misfortune of going from freedom to “captivity”. And what’s truly most terrifying is the unwavering commonality of their views. They all echo the same sentiment declaring, “This is exactly what it looked like before Castro, or Hitler”, or whomever it was that led the movement that ultimately stole their freedom. By “exactly what this looked like “ these patients tell me they mean gun control, governmental intervention in business, loss of certain freedoms of religious expression and the like. They uniformly speak of the insidious nature of freedom’s ebb. Citizens of their former nations had decried the possibility that terrible social change was in the winds believing such a thing could not possibly occur. Listening to them intently I have concluded that freedom is much easier to lose than it is to gain.

Now I understand the need for us all to listen closely to what is happening in Washington as well as wherever we live. We must critically evaluate what we hear on the news, and steadfastly maintain open and circumspect eyes. Everyone would agree our country is in the midst of dramatic change. The question of course remains as to what direction we will take. As in the case of medical prevention it is time for us all to make perhaps our most important decision. Are we willing to do what it takes to prevent the loss of something our forefathers fought so bravely to attain? Will we sit back lazily and let the chips fall where they may? Or, will we get in the game, keep up with national and international events, maintain open but cautious minds, and speak loudly if we believe our freedom to be in jeopardy?  Remember the example of medicine – no one wants a bypass. The best way to avoid a bypass is to be proactive. The same, I believe holds true for remaining free.

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