The American Society for Preventive Cardiology 30 Years and Counting

ASPC CVD PREVENTION

July 30, 2015 marks the start of the ASPC’s Annual meeting, taking place once again at the spectacular Boca Raton Resort. This year, in addition to our world-class faculty, new elements will be added to the meeting – poster presentations to be published in Clinical Cardiology as well as a Level 1 Expert’s Course in Preventive Cardiology. Over the next three months I will certainly write more about the conference and I hope many of you will avail yourselves of its offerings. (For more complete information please visit www.aspconline.org).

Today however, on the heels of the Dallas Cardio-Metabolic Health Congress (CMHC) I am compelled to write this brief note about the ASPC. The reason is simple. As I sat in the speaker’s row with my friends and colleagues Drs. Jamie Underberg, Amit Khera, and Michael Miller it became clear that the thirty-year-old organization is now firmly entrenched in mainstream education. You see, Dr. Underberg sits on the ASPC’s Board of Directors while Dr. Khera is the Secretary; I am the President Elect, and Dr. Miller is a Past President. It was truly heartwarming to have us all gathered together for the sole purpose of helping to educate our colleagues about issues such as Familial Hypercholesterolemia (FH), Hypertriglyceridemia, Lipid and Cholesterol Guidelines, and the future of HDL research and therapies.  The ASPC is growing at a gratifyingly rapid rate, as more and more physicians, ARNPs, and other healthcare practitioners embrace the doctrine that cardiovascular disease prevention must preempt intervention in order for our nation and the world at large to be able to truly enjoy optimal health. If you are not already a member of the ASPC, please consider becoming one. Also, I encourage everyone interested in prevention to join us in July. I promise you will not be disappointed.

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

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

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More Evidence that the Hallowed RCT is Just a Demigod

I know I’ve written about this issue before – and I guarantee I will write about it again – but I assure you it is important enough to be discussed until even after it has been resolved. The Randomized Controlled Trial (RCT) has become something greater than life. It is the foundation of all Guidelines; it is the subject of Board test questions; it is the trump card in all roundmanship controversies. RCTs have taken on a power beyond all other aspects of medical knowledge. And I am sure this fact represents one of Medicine’s most perilous errors. Instilling RCTs with veto power across all lines of medical debate has relegated such things as clinical acumen, understanding of pathophysiology, and good old-fashioned common sense to second-rate skills. Endowing the RCT with omnipotence has all but eliminated the need for doctors and other health care practitioners to read extensively and understand the fundamental principals of medicine. Two recent examples plainly illuminate this problem.

In one case, a woman with a history of breast cancer as well as ASCVD finished her fifth year of Arimidex. Should she continue was the question, even though the medication might have been making it more difficult to effectively manage her lipids. No study had resolved this issue and so she decided to discontinue the medication. Troubled by her decision I contacted her oncologist and asked him what his gut suggested we do. He favored continuation of the medication. We listened to his well-honed instinct and simply fought a bit harder to control her cholesterol. Last week she was one of the first to have a test to predict the value of Arimidex continuation beyond year five. It turns out that she has a very high risk of breast cancer recurrence in the absence of drug. In other words, the oncologist’s gut was spot on. Perhaps the decision saved her life.

In another case, a friend recently told me that since our conversation regarding his atrial fibrillation four years ago – when I had suggested he stop drinking seltzer and also increase his magnesium intake – he completely stopped experiencing episodes of Afib. At the time he was having such frequent bouts of arrhythmias that radiofrequency ablation was strongly advised by all his physicians. Fortunately he tried an unproved treatment (which I, an electrophysiologist, had seen work in other patients) and it was entirely effective.  By trying something safe yet unproved, he was spared a potentially life-threatening procedure.

Reflecting on how we all practice medicine, I cannot but acknowledge the fact that most of our decisions are based upon data distinct from what can be found in the RCT. The bottom line: let’s respect and honor that which makes doctors more than just a commodity – our knowledge, instinct, clinical acumen, common sense, and sometimes our depth of caring.

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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LDL Cholesterol: Sometimes the Simple Questions are the Most Revealing

Recently, after participating in a meeting attended by a few high-powered CVD researchers I returned home plagued by a most simplistic question: What is the purpose of LDL cholesterol? Please refrain from bursting into uncontrollable spasms of laughter; I am well aware that as a clinical lipidologist I never imagined such a question would have the capacity to keep me up at night. And yet it did. And so I called my faithful counsel, upon whom I can always rely to extricate me from any lipid conundrum. Tom Dayspring responded to my query unflustered, promptly sending me articles to help me find my way. I read them and this is what I realized. LDL cholesterol is essentially garbage. The story goes something like this.

Our livers manufacture triglyceride – (TG) and cholesterol – containing lipoprotein particles called VLDLs. This is old news. VLDL contains about 80% TG and 20% cholesterol. Its purpose is to nourish our organs. As these particles pass through the tiny capillaries of our various organs, enzymes called Lipoprotein Lipase (LPL) snip the fatty acids from their TG backbone, Glycerol. This too is old news. These released fatty acids are either used for energy or stored by our organs for future needs. The shrunken down VLDL particles, devoid of most of their TG energy content, are now re-dubbed. They have become LDL particles. They are cholesterol-rich. Their content represents what most people speak about after visiting their doctors – LDL-C or LDL cholesterol. Here’s where it gets intriguing. Although any lipid specialist can tell you that every single cell in our body has the capacity to make cholesterol, most believe that the cholesterol contained in LDL particles has some greater purpose. Our cells however do not need the cholesterol contained in LDL particles; nonetheless, most of us believe they use it. This belief is untrue. LDL-C is actually not utilized to any significant degree by any organ systems in human beings. Other animals may use some of it here and there, but not us. We just don’t need it. In fact, the goal of LDL particles is to get to the liver ASAP for disposal. Otherwise, these particles tend to land in places where we do not want or need them, our blood vessel walls to be more specific. You know how that story goes – plaque forms; plaque ruptures; heart attacks or strokes ensue…

So when people tell you not to worry about your high LDL-C levels, please reconsider abandoning your doctor’s LDL-C-lowering advice. And definitely don’t worry that low LDL-C levels will deprive your cells of their much-needed cholesterol. It won’t. Your cells are quite capable of making their own supply of cholesterol. On a somewhat esoteric note, it is true that the surface of LDL particles transports some vital nutrients around the body (vitamin E for one). This fact however does not imply that more LDL is better than less. We need just a tiny bit for non-cholesterol purposes. Excess does us no good, and in truth it does us a good deal of harm.

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

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

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Mayo Clinic Cardiovascular Disease Prevention Conference – a Testament to the Dedication of Healthcare Practitioners

Okay. You read the title and immediately imagined a bunch of doctors and scientists lounging on the spectacular Mexican beaches while you – if you live pretty much anywhere in the US – dig yourself out from yet another snowfall. It is true that the beach is pristine. And yes, the weather is unbeatable. But, truth be told, every speaker and attendee spent days and evenings continually holed up in a windowless conference room discussing issues ranging from exercise and diet, to Familial Hypercholesterolemia (FH), to even the impact of COPD on CVD. The meeting was excellent. Great discussions, proposals for future collaborations, some colleagues reuniting while others being introduced to a new group of associates. The ACC/AHA Cholesterol and Risk Assessment Guidelines as well as the new BP Guidelines were hotly debated.

In all, it was a wonderful weekend that enabled us to exchange ideas, consider alternate approaches to our patients, and simply grow as doctors, nutritionists, and scientists. So while American Medicine continues to be a target of mostly criticism, rest assured there are many who continue to do their part to ensure the viability and continuation of truly top-notch healthcare and research.

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From the Ivory Tower to the Trenches: A Practical Approach to the 2013 ACC/AHA Cholesterol and Risk Assessment Guidelines

The distillation of well over one hundred pages of two guidelines into a pragmatic and accessible tool for the practicing clinician is of course a monumental task. It is essential to do so though. Clinicians require clear guidance in helping them manage patients in harmony with scientific developments. To think though that science is simply and solely a regurgitation of large randomized double blind placebo-controlled trials would be foolhardy to say the least. Science – especially medical science – is so much more. The fast-paced evolution of science keeps us all on our toes. And there are so many levels to consider: clinical trials of all forms, basic science of multiple disciplines, clinical acumen borne of clinical experience, and of course good old-fashioned common sense. So the Guidelines’ authors’ use of just a single facet of science, the Randomized Clinical Trial (RCT), a priori limits the utility of the recent guidelines. Still, they must be addressed and reckoned with. Indeed like most other things in life, they are not “all bad.” Before distilling the Guideline’s into a practical approach that I personally intend to follow, let’s first put the premise of the RCT as “King” in a real-world context by examining a typical doctor’s approach to patients.

In medical schools, residencies, and fellowships all physicians are trained how to diagnose and manage patients. Take a hypothetical case. A new patient awaits your expertise as you enter the exam room. The patient has dutifully completed a multi-page questionnaire, the modern-day equivalent of a Review of Systems (ROS), Past Surgical History (PSH), Past Medical History (PMH), List of Allergies and Current Medications, and History of Present Illness (HPI). You’ve read the document prior to entering the room but you spend time clarifying the issues and creating this patient’s cohesive medical story. Then you examine him; from his right, just as you were taught in medical school. Your exam has morphed of course, emphasizing those aspects relevant to your particular specialty but still incorporating features from other areas of interest. After all, it is a whole person you are seeing, and ailments oftentimes breach systems’ boundaries as they are not constrained by artificial barriers. You examine his blood work as well as any other pertinent tests that have been performed prior to the visit. Then you think. You place the pieces of his particular puzzle in an orderly fashion; you make diagnoses; and then you create a plan. Reflecting on every single aspect of this fundamental, age-old doctor-patient interaction, consider how much of it is truly based upon solid RCT evidence. I will spare you the agony of this exercise as I’ve already done it countless times. The answer is essentially none. Where are the RCTs validating our ROS, HPI, examination from the right…? They simply do not exist. Yet, this is how we all practice medicine. And, it has worked out rather well for our patients. None of us should be handcuffed by RCTs when we evaluate and treat patients; we are all free to use any and all of the countless tools at our disposal. And frankly, the more tools in our chest, the better off are our patients. So, rule number one in addressing the guidelines is, “Remember that they are not rules.” Guidelines are not a part of the Ten Commandments. Even the authors of the 2013 ACC/AHA Guidelines acknowledge this when they state, “Guidelines attempt to define practices that meet the needs in most circumstances and are not a replacement for clinical judgment. The ultimate decision about care of a particular patient must be made by the healthcare provider and patient in light of the circumstances presented by that patient.” Translation: You the doctor should treat each and every individual patient in the manner you deem most appropriate. You must not feel shackled by these or any other “Guidelines.” With this in mind, I will now review the Cholesterol and Risk Assessment Guidelines to present an approach I will utilize in my practice. The views that follow emanate from experience garnered through practicing Clinical Lipidology and Preventive Cardiology, in addition to my personal interpretation of the literature as a whole.

Four groups qualify for statin therapy in the new guidelines, and I agree; they should all be treated. They are:

  1.  Patients with clinical atherosclerotic cardiovascular disease (ASCVD), defined as acute coronary syndromes (ACS), myocardial infarction (MI), stable or unstable angina pectoris, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease (PAD) presumed to be of atherosclerotic origin. These patients are to receive high-intensity statins.
  2. Primary elevations of LDL-C > 190 mg/dL (consistent with Familial Hypercholesterolemia, or FH). These patients are to receive high-intensity statins.
  3. Diabetic patients between the ages of 40 and 75 with LDL-C 70 to 189 mg/dL and no history of ASCVD. Patients with 10 year risk > 7.5% receive high-intensity statins while others receive moderate-intensity statins.
  4. Patients without clinical ASCVD or Diabetes Mellitus between the ages of 40 and 75, having an LDL-C 70 to 189 mg/dL and 10 year ASCVD risk of > 7.5%. These patients are to receive moderate-to-high intensity statins.

A few problems with this construct are:

  1. The Risk calculator is still shrouded in uncertainty. Many issues remain to be resolved, not the least of which is the fact that a strong Family History of premature ASCVD fails to impact risk in this system. Also, only 24,000 patients were evaluated to construct this tool which sits at the center of these guidelines and is meant to be used to determine therapy for hundreds of millions of people. Therefore, for now, when I opt to do a 10 year risk assessment I will still use Framingham Risk Scoring. I do so with the understanding of the limitations of this scoring system and the concomitant need for methods to further risk reclassify patients.
  2. The intention is to treat patients with high-intensity statins and assume an LDL-C reduction of > 50%, and moderate intensity statins to achieve a reduction of 30 to 50%. LDL-C goals are now passé in this paradigm. However, we all know that each patient is unique. Some respond very well to statin therapy; others do not. I will therefore continue to measure LDL-C (as well as LDL-P) on drug and I will continue to get my patients to goals at least as stringent as those in ATP3. There are ample data supporting the “lower is better” hypothesis. For example, the Cholesterol Treatment Trialists (CTT) study showed in both phases one and two that lower is better. The fact that we do not have RCTs that have used titration of statins to LDL goals as a primary endpoint in no way negates the overwhelming body of literature showing better outcomes at lower LDL-C , apo B, and LDL-P levels across a range of different statins. I will continue treat to targets.
  3. The high-dose-statin-absent-adjunctive-therapy (or-even lipid/lipoprotein-follow-up) concept is to me “pie in the sky.” We all know that from an LDL-C – but even more so LDL-P or apo B – standpoint by prescribing statins alone we will fall woefully short of what we have been accustomed to achieve. We also know that lower is better. Thus, by adhering to the guidelines’ advice we will very possibly see worse future outcomes. Additionally, we know from several trials that statin-related Diabetes Mellitus is dose related. JUPITER found that 20 mg of Rosuvastatin reduced 2.5 ASCVD events or deaths for every one excess in DM. Thus there is a trade-off for uptitration of statins. For me, I will use statins as a base and other therapies such as cholesterol absorption inhibition and bile acid sequestration as adjunctive therapy.
  4. ASCVD includes the presence of PAD but it does not include the presence of subclinical disease in the coronary or carotid arterial trees. This is counterintuitive. There is ample evidence that the presence of a high Coronary Artery Calcium score (CAC) or age-and sex-inappropriate Carotid Intimal Media Thickness (CIMT) predicts higher risk of ASCVD events. Even absent the copious data we have accumulated, doesn’t it make physiologic sense to ascribe as much value to disease in the vascular beds that are direct culprits for the very events we are attempting to thwart as we do to distant arteries in the legs? I will continue to use CIMT and CAC (and coronary CT angiography) in intermediate risk patients as tools to risk reclassify patients.
  5. The age limits of 40 to 75 are problematic. What do we do with a 35 year old woman with no other ASCVD risks except an LDL-C of 180 mg/dL and a powerful family history of premature ASCVD? Her 10 year risk is only 1.6% but she is too young to be treated by the new guidelines regardless of her risk score. I would unequivocally treat this woman.
  6. The absence of a significant lipoprotein and triglyceride discussion relegates the guidelines to be strictly statin/LDL-C documents. They do not attempt to be comprehensive and the authors acknowledge this fact. Thus, we should not be misled to believe that lipoproteins and triglycerides are suddenly unimportant. They are not. I will continue to assess them and manage them in a patient-centric, individualized manner. Again, every patient is different. Each one deserves his or her unique assessment and management. “One size fits all” has no place in modern medicine.
  7. Biological markers like Lipoprotein Associated Phospholipase A2 (LpPLA2), myeloperoxidase (MPO), oxidized LDL, Lp(a), and urine microalbumin have numerous studies either validating their position as ASCVD risk factors or at least implicating them in ASCVD. Though de-emphasized in these guidelines, biological markers are helpful tools in understanding our patients’ risks as well as motivating our patients to adjust their lifestyles and take their medications. I will continue to utilize them in my practice of “Interventional Prevention.”

In summation let us remember that these guidelines are not law. They are based entirely upon a mere 25 “highest level” clinical trials, ignoring thousands of “lower level” trials, human biology and physiology, and clinical acumen. To some extent I would say they are so limited in scope by inappropriately-stringent data-entry criteria that they have become Ivory Tower, clinically-blind advice. Their very construct diminishes their real world relevance.  Ironically the system suggested in the guidelines has itself never been validated by the very type of RCT evidence demanded by the guideline authors. Something is surely wrong with that. Yet on a positive note the new guidelines are simpler than ATP3. Reliance more upon Global (Total) Risk rather than individual risk factors makes it easier for clinicians to make recommendations. Still, simple is not always good. As outlined above, I intend to use the guidelines as a foundation upon which to build a more dynamic and plastic way to approach the patients in my clinical practice. I refuse to await trials that may never appear. Instead, I will continue to avidly follow the literature, eagerly learn from my colleagues, and diligently incorporate a wide gamut of data to render the well-considered recommendations I ultimately share with my patients.

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

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High Cholesterol Levels – Time is Plaque

In the initial days of thrombolytic therapy (potent blood thinners used to treat heart attack patients) we had a saying that, “Time is Muscle”. The intent was of course to get our patients treated as quickly as possible, understanding that the longer their arteries remained closed, the more heart muscle would be lost. More damage meant worse outcomes. And so we got faster and faster, ultimately treating our patients within minutes of their initial evaluation. This need for speed has been brought into the era of acute interventions, the stents. Now we speak of door to balloon times and all hospitals boasts of their superior swiftness. The faster we get our patients to the cardiac catheterization lab for definitive treatment to stop their heart attacks, the better they do.

Analogous to the situation with heart attack patients, individuals with extremely high LDL cholesterol are now known to develop plaques in their arteries in accord with the duration that they experience their high lipid levels. Some children have such high cholesterol levels starting even from when they’re in utero; they develop heart attacks before the age of five. This of course is quite rare, but it does illustrate the importance of both cholesterol levels and time in plaque formation. For proper prevention we need to adopt a greater sense of urgency, one that embodies our understanding that the longer one has high cholesterol levels, the more likely he or she is to develop vascular disease. In short, we ought to start declaring, “Time is plaque!”

Please read more about treating high cholesterol at www.preventivecardiologyinc.com.

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National Cholesterol Education Month – check your cholesterol levels

couple bike riding

Today September – National Cholesterol Education Month – comes to a close.

Two weeks ago I participated in the First International Familial Hypercholesterolemia (FH) Summit, hosted by the FH Foundation and attended by 120 cholesterol experts from around the world. It was an inspiring event. Katherine Wilemon, a young heart attack survivor and bearer of the not-so-uncommon and far-too-frequently deadly genetic cholesterol disorder FH, led the charge for FH awareness and concomitant therapy. We all left the meeting brimming with optimism.

Last week I had the privilege of delivering Grand Rounds at UCI, again on the subject of FH. The message was well received; if doctors fail to consider FH we will of course fail to identify it. Absent its identification, treatment cannot be rendered. Translation – we must put FH on our radar screen.

While many of us are working tirelessly to “spread the word”, naysayers blather uncensored on the internet and in the popular press about the dangers of cholesterol lowering drugs and the fallacy of the “cholesterol hypothesis”. Never before has medical science so clearly identified a culprit for heart disease and never before have we had such wonderful ways to mitigate the threat. Yet the gains we make are eroded daily by these adversaries. What are we to do? Somehow less knowledgeable but more vociferous folks have usurped our podium. Somehow the public has lost faith in medical science, instead choosing to believe oftentimes fork-tongued purveyors of “anti-science” spreading the paranoid perspective that drug companies and doctors conspire solely for their own advancement. How do we fight and win this battle? I believe that victory rests in patients once again understanding why it is that doctors deliberately choose their arduous path. Doctors don’t whimsically decide to devote ten or more years of their post-college lives to incomparably hard work and abysmal pay. The decision to become a physician is always well-considered. It is also a choice that can be made by only the brightest and hardest working young men and women. So what is the common denominator that drives these people to enter an exhausting and oftentimes unappreciated profession? Simply put, it is to help others. Doctors become doctors because they care. This I can promise you to be true. So when your doctor offers advice about cholesterol (or other issues for that matter) please consider from whence the advice originates. Contrast that to the recommendations you may see or hear on the internet, through the media, or even from an ostensibly well-meaning friend.  Doctors have their patients’ best interests at heart. The same is not so clear about the naysayers.

So at the close of National Cholesterol Education Month, do yourself and your loved ones a favor. Check your cholesterol levels. Then speak with your doctor. Be sure you’re being treated as well as we can treat you. It really could save your life.

Learn more about comprehensive preventive cardiology at preventivecardiologyinc.com

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Cholesterol and Vascular Disease Part 6: LDL-Apheresis and Other Novel Cholesterol Strategies

September is National Cholesterol Education Month. In support of this important educational initiative we are republishing our six part series on cholesterol and the role it plays in cardiovascular disease.

Note: Seventy-one million American adults have high cholesterol, but it is estimated that only one-third of them have the condition under control.

Today’s final post in my six-part series on cholesterol examines one FDA approved non-medication treatment for severely elevated LDL cholesterol, and three novel medications on the horizon.

LDL-Apheresis is a non-drug therapy for patients with vascular disease and LDL-C > 200. It is reserved for patients with a genetic disorder called Familial Hypercholesterolemia (FH), or those individuals who cannot tolerate standard medications but still have very high LDL levels. Therefore, this treatment is clearly not for everyone. In a manner similar to dialysis, patients are connected to a filtering machine through two IV lines. Blood is withdrawn from one arm, circulated through a series of filters and returned to the body through the other arm. Typically the procedure is performed every other week. Each treatment results in a 60% to 80% reduction in LDL particles. After treatments, the LDL will rise steadily until it can be lowered once again with another therapy. Although LDLs do increase after a treatment, studies have demonstrated a nearly 75% reduction in cardiovascular events when patients are treated with LDL-Apheresis. Thus, LDL-Apheresis is a viable option for high risk patients. I am very fortunate to be able to run one of the forty or so centers in the USA, and I am happy to say that not only is the procedure extraordinarily well tolerated, but also the lipid effects are nothing short of remarkable.

As for the medications on the horizon, three deserve immediate recognition: Mipomersen, Lomitapide, and REGN727. These are all currently “experimental” but deserve mention not just because they will likely soon be on the market, but because each one represents a truly fresh way to lower LDL.

  • Mipomersen, licensed by Genzyme, is a second generation antisense oligonucleotide that is administered weekly by injection. It dramatically lowers LDL. The English translation is that this drug thwarts our body’s LDL production mechanism at the DNA level. DNA’s job is to produce mRNA in order to translate DNA’s protein-producing knowledge into the actual creation of proteins. Mipomerson binds and inactivates the mRNA that carries the code for the essential protein in every LDL particle, apoB. Without apoB, LDL cannot be created. Mipomerson does not block cholesterol production; it stops our body from producing too many LDL particles. Very different from the way statins work! Read More…

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Distortion of Scientific Findings: Here We Go Again!

“Baby’s Blocked Belly Tied to Low Cholesterol” is the headline of today’s Medscape article reporting on a just-released JAMA publication. Contrast this with the article’s actual title, “Plasma Lipids, Genetic Variants Near APOA1, and the Risk of Infantile Hypertrophic Pyloric Stenosis”. Notice a difference? Accurate headlines don’t sell papers, or blogs. Apparently our interest is peaked only by findings or events that have an immediate and preferably negative impact. One would infer from the headline that low cholesterol is bad, causing the “blocked bellies” in babies. In no way does this study actually come to such a conclusion. Instead it reveals that the genes causing pyloric stenosis reside near those controlling certain lipid levels. Both sets of genes can experience changes (polymorphisms) resulting in abnormalities. So, abnormal lipids in these children are more likely the result of being in the wrong place at the wrong time. It is likely that the two disorders occur concurrently not because of causality, but rather misfortune. Low cholesterol is not necessarily causing the pyloric stenosis even if it is associated with the disorder. Similarly, pyloric stenosis is likely not causing the abnormal cholesterol.  The bottom line again; read everything with cautious eyes.

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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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