Internal Medicine Of Southwest Florida Newsletter
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Featured Article
HDL Cholesterol
Weight Loss...What is Working
High Fiber Recipe
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Issue: # 12Feb/March/2011

Greetings!  

 

I have been reading a lot about HDL cholesterol these past few months. In fact, in October of 2010 the Journal of Clinical Lipidology presented a symposium dedicated to this topic.  The first article in this newsletter is dedicated to HDL cholesterol.  There is a significant amount of ongoing heart attack and stroke risk which can be attributed to low HDL cholesterol and thus awareness of this cholesterol type needs to be raised.
  
The desire to have a more ideal body weight is felt by most of us. The associated risk of numerous diseases occur when our Body Mass Index exceeds 27. A BMI of 27 or less should be our first goal for a healthy weight. A BMI of 25 is considered ideal body weight. There are many quick fix weight loss programs and unproven or undisclosed products being used to help people lose weight quickly- these programs do not work long term.   These quick fixes don't teach you to permanently change how you eat in order to maintain a correct caloric balance (calories in vs. calories burned).  The second article will explore using Pure Encapsulations PureLean Protocol for healthy weight management. 
  
Lastly, I have made a recipe for another healthy, high fiber dish which I hope our readers will try out.

 

 

 

Is HDL Cholesterol Important?

High CholesterolLow HDL Cholesterol Raises Heart Attack Risk.

 

Cholesterol is one type of molecule that is included in a family of of molecules known as lipids.  Cholesterol is important for cell membrane integrity, a source for steroid production and bile salts and it is also a source of fatty acid/energy for our body and cells. Cholesterol along with triglycerides is moved (transported) from our digestive system to numerous cells and tissues through carrier  molecules known as lipoproteins.
  
Lipoproteins are complex structures in which cholesterol and other lipid substances are "dissolved" into a round shaped complex which due to its chemical properties allow the particle to move in a water solution. Anyone who has cooked knows that fat and water don't mix. Lipoproteins make it possible for our body to move cholesterol and fatty molecules through our mostly water blood circulation. Imagine the various lipoproteins being similar to "soap bubbles".  Lipoprotein subtypes include LDL and HDL.  There are other subtypes but doctors mostly discuss LDL and HDL cholesterol.  When you see and hear these terms we really are talking about LDL and HDL lipoproteins (the carrier forms that circulating cholesterol moves between). 
  
For the past few decades the scientific community has established that cholesterol (and especially elevated LDL cholesterol) drives the disease process known as atheroclerosis (hardening of the arteries).  Learning from this pathology, the medical and pharmaceutical community has developed different products to lower/modify primarily LDL cholesterol levels.  The most powerful drug class to lower LDL cholesterol are known as statins.  Over the past 2-3 decades statins have proven to significantly lower LDL cholesterol and this has translated to substantial reduction in heart attack rates (and all cause mortality I might add).  Stroke rates are lowered with statins but not nearly to the same degree as heart attacks.
  
A recently published article from the Annals of Internal Medicine looked at 20 randomized clinical trials involving statins which involved statin medications and reported and followed HDL levels both at baseline and on treatment.  The cumulative patient years experience when the studies were combined and analyzed was over 543 thousand years (that is a lot of power as it relates to data)!  What did they find?  Statins did lower heart attack and stroke risk regardless of HDL cholesterol levels.  Subjects with low HDL levels pretreatment still had significant recurrent events/ongoing risk relative to individuals with normal HDL levels.  According to the article's data each 10 mg/dl decrease in HDL was associated with 7 additional heart attacks and 4 additional cardiovascular events per 1000 patient years despite statin therapy. Statin therapy reduced events 4/1000 years (heart attack and other cardiovascular events were each reduced by 4).  The magnitude of statin-mediated reduction in heart attack and CVD events is about equal to the difference in events associated with a 5-10 mg/dl increase in HDL.  This means that for low HDL patients, if HDL is allowed to remain low the benefit of statin therapy is being equally offset by the low HDL.  The implication of this information is that physicians may need to target improving HDL in low HDL patients. 
  
What does HDL cholesterol do?

 

As it turns out our understanding of HDL lipoproteins remains incomplete.  At the basic science level we are learning a lot about HDL cholesterol.  The main function of HDL cholesterol is its involvement in what is called reverse cholesterol transport.  As stated at the top of the article cholesterol is utilized by our tissues and cells for a variety of purposes. Endocrine (hormone producing) cells can utilized cholesterol. Other cell types cannot utilize or breakdown cholesterol. If cholesterol is not used by a cell, it cannot be broken down-it either collects in the cell or it has to transferred back into the bloodstream to be recirculated. HDL lipoproteins are intimately involved in this movement from our cells back into the blood stream and ultimately to the liver for either elimination through bile and stool or repackaging to be taken to other tissues and cells. This recirculation of cholesterol by HDL lipoproteins is known as reverse cholesterol transport.
  
Another set of functions that HDL lipoproteins are involved in include the inflammation pathway.  Inflammation in biological tissues increases cellular death.  Inflammation is involved in the disease process of arteriosclerosis.  If HDL is functioning properly it helps the movement of unneeded cholesterol out of cells and it reduces inflammation while promoting healing.  If our arterial cells (endothelial cells) become over-burdened with cholesterol then the cells excrete inflammation signals to try to get a special group of white killer cells known as macrophages to come and scavenge the cholesterol up (imagine a packman eating cholesterol).  HDL lipoproteins secrete chemical signals which allow the macrophages (packmen) to release some of that accumulated cholesterol back to the HDL lipoprotein and thus allow the cholesterol to be moved back to the liver and other tissues for clearance.  A recent chemical technique using a chemical analysis called mass spectrometry has allowed us to understand protein expression in HDL lipoproteins.  This information has revealed 2 families of protein reside in HDL lipoproteins.  These protein classes are involved in regulating inflammation and specifically the clotting of ruptured plaque.  Ruptured plaque and the ensuing clotting reaction to it is what an acute heart attack really is.
  
How can HDL be increased?

 

Firstly there are things we can do in the behavior department to help optimize our bodies own production of HDL.  Don't smoke. Smoking lowers HDL levels.  Don't get heavy and if you are heavy, lose weight.  Being overweight or obese results in numerous adverse affects on lipoprotein metabolism that give an individual, high total cholesterol, elevated triglycerides, elevated glucose and low HDL cholesterol.  Often low HDL cholesterol is in the company of these other findings.  The more lipoprotein abnormalities a person has the higher the risk and rate of heart attack in the future.  Exercise more often.  Aerobic and even more aggressive anaerobic exercise raises HDL levels.  As stated earlier even a mild improvement in HDL of 5-10 mg/dl can significantly alter you risk for heart attack and other cardiovascular events.
  
Niacin is both a vitamin and a drug. It positively benefits all aspects of the lipoprotein profile and even raises adiponectin levels (which might translate to less body fat).  In high doses niacin becomes a drug.  Niacin has proven benefit for reducing cardiovascular disease and improving survival from coronary artery disease, starting with the Coronary Drug Project but includes favorable data in several combination therapy trials including the CLAS, FATS and HATS trials.  To date, in my opinion, Niacin is the best HDL medication and while its mechanism of action is yet to be fully understood, it modifies all of the lipoprotein classes beneficially.  Its side effects have limited its use and due to the nasty and predictable side effect of flushing, many physicians don't offer it to patients who are potential candidates.  The flushing problem usually goes away with ongoing use.  If I have a patient with low HDL cholesterol and an established history of a prior heart attack and or vascular intervention such as an angioplasty or aneurysm repair, I will definitely recommend this compound.  There are two ongoing trials looking at using Niaspan (a name brand formulation of niacin) in conjunction with statin therapy to evaluated for effectiveness.  These trials are known under the abbreviated names AIM-HIGH and HPS2-THRIVE .  The latter trial involves a special combination medication of Niaspan and laropiprant. The laropiprant compound is designed to improve the flushing side effects and thus improve compliance with higher dose niacin.

Not all over the counter niacin is the same.  Specifically no-flush niacin preparations do not work in people.  The no-flush products have niacinamide hexanoate as the active ingredient. This molecule works great in rabbits but humans cannot metabolize/use it into the active niacin- this is why we don't flush when it is taken.  Two name brand slow release niacin preparations that do give results include ENDUR-ACINŽ and Slo-Niacin.  Regular release true niacin will work well. It is the cheapest form of niacin but also has the most flushing associated with it. It also has a very short activity level and thus is usually dosed 2-3 times a day which makes it more inconvenient.
  
Another class of medications known as fibrates have been extensively studied as well.  Examples of fibrates currently available in the US include gemfibrozil (Lopid) and fenofibrate (Tricor and others).  Gemfibrozil has shown definite improvement in outcomes and survival but its use has fallen out of favor due to the proven benefits of statins (and better outcomes with statins). Gemfibrozil is more risky to use when combined with statins and this too has resulted in far less prescribing than in the past. Fenofibrate is safe in combination with statins and thus this is written for more than gemfibrozil.  It's benefit for low HDL across the board has not shown statistically significant benefit and thus it isn't written for very much either.  There is a caveat to this medication however.  Sub analysis data does show that if a patient has significantly elevated triglycerides and low HDL then fenofibrate does offer significant additional benefit. 
  
What is in the future to treat low HDL cholesterol?
  
Cholesteryl Ester Transfer Protein plays an important role in HDL lipoprotein metabolism.  One medication that showed significant promise, known as torcetrapib was found to increase cardiovascular events and mortality when added to high dose Lipitor in patients with established coronary artery disease.  There is some ongoing debate as to why this happened.  One off-target effect of this medication was that it elevated blood pressure and thus it is felt this blunted the benefit of targeting this protein.  On astute scientist- author Bela F. Asztalos PHD has pointed out that the blood pressure effect alone doesn't explain the unfavorable outcome difference as the amount of blood pressure elevation didn't account for the amount of unfavorable outcomes observed.  Cancer, infection and sepsis rates were substantially higher in the torcetrapib group.  It is possible that while inhibiting CETP increased HDL (and it really did by an average of 50%), the HDL might not have been functioning.  There are genetic linked cases of very high HDL in animals and humans that show increased (nonprotective HDL benefit) of athersclerosis.  The idea is that while these individuals are genetically producing high HDL levels it appears that the HDL is not functioning in the removal of cholesterol from cells/tissues.  There are two other compounds in this drug class currently being studied for clinical use. One is in a therapeutic trial and will be completed in approximately 3 years.
  
Infusion of HDL lipoprotein is another area of ongoing research/study.  The day may come when clinicians will be able to literally intravenously deliver lipid poor HDL lipoprotein and this substance would sop up cholesterol from unstable plaque and macrophages (remember the packmen?). There was already a small study done to look at this principle.  A genetic variant of HDL called Apo1 Milano was mixed in a complex of phopholipids and given weekly x 5 infusions within 2 weeks of a patient presenting with instable angina or heart attack.  Using intravascular ultrasound techniques it was shown that atheroma volume was significantly reduced in the treatment group. This product was purchased by Pfizer in the hopes of bringing it to market but manufacturing difficulties complicated this.  Pfizer has subsequently sold this compound to another company (The Medicines Company) in 2009.   A different infusion compound is being researched in Canada.  It is a modification of a different substance which while showing promise resulted in an unacceptably higher incidence of liver inflammation.  This substance contains a apo A-1 protein which when combined with soybean derived phosphtidylcholine resembles natural human HDL cholesterol.
  
By mouth drugs which include small molecules that can increase the Apo A-1 protein are also in the pipeline.  Apo A-1 if increased should result in a higher production of HDL lipoprotein related cholesterol.
  
What about diagnostic testing that might improve who would benefit from HDL targeted therapy?

 

Suffice it to say that with ongoing deeper understanding of the complex protein carriers and broader function of HDL lipoprotein there will likely be commercially available tests to help physicians know whether a persons HDL cholesterol is functioning normally or not.  Assays that potentially could be developed include measuring the activity of certain parts of the reverse cholesterol transport process.  Perhaps we will be able to develop a nuclear test that literally "lights up" the reversible cholesterol transport system.  We may also be able to take very high HDL people and analyze their HDL function to see if they have higher risk of disease instead of the assumed lower risk. As stated earlier high HDL does always translate to protection (especially when very high). 
  
Currently we can analyze lipoprotein sub-fractions using advance lipoprotein analysis techniques and potentially interpret unforeseen risk and/or protection that simple HDL measurements might miss. For instance, a low alpha-1 HDL level is one of the most significant predictors for recurrent cardiovascular disease events when analyzing subjects in the Veteran's Affairs HDL Intervention Trial (VA-HIT).
Weight Loss/Management

WeightlossWhat Is Working

 

Internal Medicine of Southwest Florida has had the benefit of a dietitian on staff for approximately 2 years.  Ms. Russo and I have been striving to help overweight persons safely lose weight in order to derive the benefits of optimal weight. 
  
Recently my son told me how on an flight back from the Northeast he overheard a very zealous salesman touting the benefits of his "magical weight management program".  The sales pitch emphasized how we are being poisoned by the food industry with genetically modified foods and toxic chemicals. Really we are poisoning ourselves with too many calories and poor nutritional choices. His product line apparently involved various toxin removers and a cycle of cleansing programs.  From my son's reiteration (he was simply a fly on the wall) there was a several week program involved.  Basically if you purchased all the supplements and various toxin cleansers and followed the program you would lose significant amounts of weight.  The salesman made a point that there wasn't any dieting involved.  By the description provided, however, that is exactly what the program did.  The customer was so involved in following various cathartic regimens along with manufactured meals, etc that resulted in some artificial weight loss through fluid loss and some real weight loss through caloric deprivation.  This story simply leads me to the main message: In order to effectively lose weight one must eat less calories than used. This is not easy to do and that is manifest in the unprecedented epidemic of obesity in the developed world.  
  
In a past newsletter, I have reviewed and described the present (and now one not available) medications that may be used to assist in weight management. I am sorry to tell you folks again- there is presently no medication safe and effective for long term use in weight management.  There are some options for short term, medically supervised therapy (3 months FDA approval).
  
As many readers know, we can measure a persons actual resting metabolic rate by breathing into a tube which quantifies carbon dioxide production (and thus infer calories being burned).  Knowing a person's metabolic rate helps us to know with good precision what limit in calories will be needed to affect weight loss/change.  In order to have sustained weight loss a person who is overweight must be willing to permanently alter their diet either through different food choices or altered portion size.  Seeing Marcy Russo will result in an expert education on how a person's personal diet is perhaps less than ideal.  She can inform you and this can result in personal decisions about how to permanently modify your diet. 
  
I personally had to make permanent changes in my diet (and reinforce my exercise habits) in order to successfully achieve and maintain appx 25 lbs of weight loss.  One among many changes I made was to incorporate a meal replacement into my dietary plan.  Specifically, I have used Pure Encapsulations PureWeigh Meal beverage, their PureLean protein replacement and their ProBasics formulation (all at various times).  My strategy is to use their products in the morning in about 6 oz of skim milk.  I also supplement with fiber, either in the form of ground flax seed or lately I have discovered their PureLean Fiber product which I am using 2-3 times daily before meals. For weight maintenance I have this "shake" each weekday along with appx 6-8 walnuts and 1/2 piece of fruit (usually apple).  I have plenty of water especially in the morning.  Additionally I usually arrange my own lunches which are high in fiber sources while avoiding deserts.  If a large amount of weight loss is needed the PureEncapsulations products can be used with each main meal along with much smaller portioned meal plans (significant calorie restriction).
  
I encourage those readers who are overweight or obese to consider a visit with Mrs. Russo to review your current diet history and preferences. Let her assist you in making permanent fixes to your meal planning. Perhaps knowing your exact metabolic rate will help get weight loss off with a minimum of discomfort. If, like me, you find it simplifies the process to use a highly nutritious, protein enhanced meal replacement/supplement in a convenient and pre-meaured product to help you keep your total calories down, I would submit this is far safer and more sane than trying to chase the latest medication or other gimmick that will be offered in the newspaper or commercials.
  
If you are on Coumadin (warfarin) there will be some concerns using some of these products due to interaction potential with some of the nutrients/food sources (such as green tea extract and low doses of vitamin measured in some of the products). If this applies to you, discuss your concerns with your attending physician before using any of the products.
A High Fiber Recipe
White BeansI keep trying to find new ways to make nutritious meals.
  
This recipe is a result of experimentation in the kitchen.  Feel free to alter the recipe to suit your palate. Perhaps more water with a "soupier" texture would be preferable. Quinoa is a high protein containing grain that most of us haven't eaten. It is also high in fiber.
  
Northern White Beans with Quinoa and Barley  
  
Ingredients: Northern White Beans 1/2 cup. One medium/small onion. 1-2 cloves of minced garlic. One-two carrots. 2-3 tablespoons olive oil. 3-4 cubes/teaspoons chicken, beef bullion or vegetable stock. 1/2 cup quinoa. 1/4 barley (pearled or precooked/5 minute). 1/8 red pepper flakes. 4 cups of water. Fresh green onions chopped (optional).
  
Soak overnight: 1/2 cup northern white beans, rinse and drain when ready to prepare dish.
  
Dice- one small to medium onion. Mince garlic cloves.
Cut-one to two carrots.
  
In a 4-5 quart saucepan add 2-3 tablespoons of olive oil over medium heat. Add the carrots, garlic and onion and saute until onions clear. Add the presoaked beans.  Add 3-4 cubes of chicken or beef bullion (dehydrated vegetable stock could be replaced at 3-4 tsp). Add 1/8 red pepper flakes and combine until vegetables and beans are coated.
  
Add 4 cups of water and bring to a boil.  Simmer, covered appx 20-25 minutes.  If uncooked barley is used add it when boil begins (1/4 cup).

After 20-25 minutes simmering add 1/2 cup quinoa.  Simmer another 20 minutes. If precooked barley is used add it (1/4 cup) 5 minutes before simmer is finished. Beans should be tender at this point and the quinoa will have expanded to a light fluffy grain.  Serve as a side dish/carbohydrate exchange. Add some chopped green onions at time of serving for additional flavor (optional).
Thanks for your continued patronage to Internal Medicine of Southwest Florida.  I hope the information in this newsletter was informative and useful. If readers which to have specific topics or diseases covered in future newsletters, please let us know.
  
  
Sincerely,

 


Raymond Kordonowy MD
Internal Medicine Of Southwest Florida

 
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