Saturday, June 30, 2012

Preserve your Beta Cells, Its hard to find new ones

Diabetes Care -  July 2012 volume 35 Page 1406-1412

Beta cell Function Preserved after 3.5 years of intensive Diabetes Therapy

This study demonstrates  Beta cell function can be preserved with early aggressive therapy for patients with type 2 Diabetes

Current approaches to Diabetes management usually go in a step wise method starting with one drug metformin and then adding other medications as needed depending on the progression of the disease.This approach leads to some thing called treatment inertia and a continuous progression of Beta cell failure. The progressive Beta Cell failure was best demonstrated in a classic study, UK Prospective Study ( UKPDS ) , one of the first studies to demonstrate that achieving an A1c of 7 reduced the risk of developing Eye , nerve and kidney damage.

Study design
Patients were 21 to 70 years old treatment Naive type 2 Diabetes diagnosed within the previous 2 months.
All patients were initially treated with metformin and insulin  ( Novolog mix/ their protocal )for 3 months  and then divided into 2 groups and followed for 3.5 years

Group 1 continue Metformin and Insulin
Group 2  switched to Triple therapy Metformin , Glyburide and pioglitzone

The medications in both groups were adjusted to attain excellent A1c results
Group 1 average A1c  6.3 at the end of the study
Group 2 average A1c  6.59 at the end of the study

 Beta cell function was preserved for 3.5 years in both groups

 This study demonstrated that intensive therapy with insulin and metformin at the time of diagnosis of Type 2 Diabetes  followed by multiple oral agents or insulin can preserve Beta cell function. Treatment inertia fostered by by the stepwise approach to glucose control may not be the best thing for your Beta cells.

Have fun , Be smart , Avoid treatment inertia and preserve your Beta Cells
David Calder, MD

Friday, June 29, 2012

Dental floss, Teeth Cleaning and Your Heart

one more article from the June issue of the American Journal of Medicine, Page 568

The Association of Tooth scaling and decreased cardiovascular Disease: A nationwide population based Study  (Taiwan )

The article reports that 30 % of all deaths in Taiwan are cardiovascular related.They point out that atherosclerosis is not just  a cholesterol storage problem but is "a sustained dynamic and inflammatory process in vasculature".  Their study was to evaluate the role of poor oral hygiene and peridontal disease and cardiovascular disease.
Their study included 21,878 persons > age 50  who had at least 1 tooth scaling in 2000 and compared them to a age and risk group who did not have tooth scaling.The study groups decreased to 10,877 people who had tooth scaling and 10,989 people who did not receive tooth scaling and were then followed for 7 years.

   Tooth scaling was associated with a decreased risk of myocardial infarction and stroke
       * People with poor oral hygiene had a 24% to 35% increased risk of heart disease
          and a 1.2% to 3% increased risk of stroke
       * Greater risk reduction was obtained with higher frequency of tooth scaling

These finding support tooth scaling in addition to daily brushing may reduce the risk of vascular disease

  I always try to look at absolute numbers along with the relative % risk reduction used in research to compare treatment and non treatment groups. The absolute numbers adds a little more reality to the results. I have included the absolute numbers below if you are interested.
                                                   Total #           no tooth scaling                        tooth scaling
Acute Myocardial infarct            408                     239                                           169  
Stroke                                         2062                   1099                                          963

Have fun , Be Smart  Brush Your Teeth  twice a day, Use Dental Floss and have your teeth inspected
                                   and cleaned at least twice a year
David Calder,MD

Confession -  My poor Dental flossing -- >Techniology to the rescue , I hope.
 I  have never been good with the teeth flossing process . I just never got into the routine until now. My dental hygienist  suggested I try the Phillips Sonicare device.  This device uses compressed air mixed with mouth wash to clean my teeth along with brushing. I  use it at least once daily now. I am eager for my visit next month to see if it has made a difference.

Tuesday, June 26, 2012

AMR101 , a new medication for lowering Triglycerides

 AMR101,  the moment of truth is approaching. The FDA will make a decision within the next few weeks on whether to approve or not approve this medications for the treatment of high triglycerides.

AMR101 is a prescription grade omega -3 -fatty acid that will hopefully be approved for the treatment of very high triglyceride levels over 500 mg/dl and the first in this class of medications approved for treating triglycerides in the 200 to <500 mg/dl range.

AMR101 is ultra pure 96 % EPA( ecosapentaenoic acid )
They have 2 studies documenting effectiveness and safety of this medication in reducing triglycerides with out elevating LDL levels. they also demonstrated favorable results with Apo b , Non - HDL cholesterol and inflammatory markers. the safety profile was comparable to placebo. ( Anchor trial and Marine trial ) another trial ( REDUCE-It ) to demonstrate the effectiveness in reducing the risk of cardiovascular disease  will be started soon.
Another study , Jellis study , using AMR101 was done in Japan and demonstrated effectiveness of 1.8 grams of purified EPA in reducing the risk of cardiovascular disease. Please see my Blogs from Jan.
 2012 for more details.
I believe this medication will be approved by the FDA and will be a useful addition in managing elevated triglycerides.

Have Fun , Be Smart and review the articles below and my other  omega 3 Fatty acid blogs from Feb..
David Calder, MD

Diabetes ,Triglycerides, Fish Oil and Heart Disease

Yesterday we discussed why the ACCORD study failed to demonstrate a reduction in the risk of heart disease with combination of simvastatin and fenofibrate .

For those of you who just want a quick summary of todays blog , just read the bold print.

Lowering Triglyceride levels and raising HDL Cholesterol is a continuing challenge. 
Life style changes with weight loss and increased exercise and correcting high glucose levels work to a certain degree .  Our choices of medications have been limited primarily to fibrates such as fenofibrate  , Niacin and Omega -3 -fatty acids ( fish oil ) .

 I was always reluctant to use fibrates because of the increased risk of Rhabdomylosis when combined with a Statin and Niacin was difficult to use because of site effects.   This left me with Omega -3-fatty acids that had its on set of problems. It was only recently that we had an FDA approved source of purified fish oil with each capsule  containing 840 mg of EPA =DHA. ( Lovaza). Cost became a factor because of the number of pills required to be effective.  All of the above resulted in my having patients use over the counter  brands of fish oil. Using over the counter medications made me uncomfortable but I did find that the results were good . I was encourage by a  recent article in Consumer Report  ( January 2012 page11) verifying that most of the over the counter brands did actually contain the amounts of EPA ad DHA found on the label.

 There is an article in the January 2012 Internal Medicine News that  is reviews more good news for us Fish Oil lovers. There may be another FDA approved source of fish oil available soon.

Fish Oil Works to lower Triglycerides
 AMR101 is pure EPA. There initial study (ANCHOR Trial ) was in a group of patients with high cardiovascular risk on Statins with LDL cholesterols of 100 mg/dl  or less and Triglyceride levels between 200 and 500 mg/dlAMR 101 2 gms/day and 4 gms/ day reduced triglycerides 10.1% and 
22 % respectively. 

 Another study  using the same medication was done in patients with fasting triglyceride levels of at least 500mg/dl .This study , MARINE Study, reported in the American J. Of Cardiology 2011;108:682-90 found that 2 and 4 gms/day of AMR101 reduced Triglyceride levels 20 % and 33 % respectively. 

These two studies provide more evidence that Omega 3 fatty acids work and seem to be more effective in patients with higher triglyceride levels.

Will Fish oil reduce my risk of developing heart disease ?
        stay tuned
                                                                       Have Fun , be Smart and Defeat Diabetes
                                                                       David Calder,MD


Omega -3 - fatty acids and Heart Disease

            Hint ; save 39.2 seconds of your time by just reading the highlighted area

We know that Omega 3 fatty Acids , EPA and DHA, in Fish Oil  reduce triglyceride levels but do they reduce the risk of having heart disease. 

There is one study done in Japan, Jelis Study (Japan EPA Lipid intervention Study) reported in Lancet 2007;369: 1090-8

 This study was included 18,000 patients with and without heart disease with total cholesterol of 251 mg/dl (6.5 mmol/L ) and LDL of 171 ( 4.4 mmol/L ) and randomized to a low dose statin alone or a statin plus 1.8 grams of EPA purified from omega - 3- fatty acids in fish oil and followed for an average of 4.6 years.
 Results ;
       Statin only group  --- ------------     3.5%  had a major coronary event
       Statin  plus 1.8 grams of EPA --   2.8%  had a major coronary event

A 19% relative risk reduction in the group receiving 1.8 gms of EPA

 There was a followup analysis of this study reported in Artherosclerosis 2009 may:204(1):233.
 This analysis looked at people in the Jelis study with elevated Triglycerides > 150 mg/dl and
  HDL < 40 mg/dl. In this higher risk group, EPA treatment resulted in a 53% relative risk reduction.

There is another planned study - REDUCE IT ( Reduction of Cardiovascular Events with EPA intervention trial ) that will specifically look at the effects of Triglyceride reduction  and cardiovascular risk. Hopefully this study , to be completed in 6 years ,will provide us with a more definitive answer .

For now , Omega 3 fatty acids , are still my first choice.

Have fun , Be Smart and Defeat Diabetes
David Calder,MD

Monday, June 25, 2012

Diabetes, Dealing with residual risk

Diabetes , dealing with residual cardiovascular risk

Dysfunctional lipids is primarily a problem for people with type 2 Diabetes however no one with or without diabetes is immune from the risk associated with elevated LDL Cholesterol , Triglycerides and low HDL .

Helping myself and my patients deal with lipid problems has been an interest of mine for many years.Multiple guidelines are available from the American Diabetes Association , Endocrine society and others. These guidelines are continually updated as more information becomes available. My initial plan was to reproduce and discuss the new guidelines . I reviewed some guidelines and decided that you can look up and read the guide lines yourself. I decided instead, to share my in the office approach to lipid management  that also evolved over years.

 I am not recommending my approach to you. Do not make any changes in your treatment.Your doctor knows you and is the best person to guide your treatment. My discussion below is help you  become more aware of treatment options to discuss with your physician.

Most of us
 To start with, most younger people ( < 40 years old )with type 1 Diabetes did not have  significant lipid problems . I tried to follow their lipid profile each year and managed any lipid problems that developed.
People with type 2 Diabetes were more of a challenge and presented a number of treatment challenges. Most presented with mild abnormalities  with LDL in 130 to 150  mg/dl ranges , HDL is the high 30's range and triglycerides 200 to 400 mg/dl range. These people responded to correcting their A1c to  7,  Mediterranean style low fat diet ,weight loss and adding a statin if necessary.  I recommended the newer more potent statins such as Lipitor ( atorvastatin) and later Crestor ( rosuvastatin )when it became available . Cost was often a problem and zocor ( simvastatin ) was my choice. The initial dose of these medications was the most effective at lowering cardiovascular risk with the lowest number of side effects. Subsequent dose increases were less effective ( see my recent discussion on the rule of 7 ) and were associated with more side effect , muscle complaints.
 The initial dose along with diet and glucose management often resulted in dramatic drops in LDL and Triglyceride levels . HDL levels did not usually respond well to treatment.

My recommended target goal for LDL in this group is 70 mg/dl and Triglycerides of <150 mg/dl.
For those people with triglycerides  not responding to the above approach I usually started with a trial of Omega 3 fatty acids .  Initially over the counter omega 3 FA were available and the usual effective dose was 4 grams . I was always concerned about the over the counter medications but they seem to work. Finally a FDA approved omega 3 FA was approved , Lovaza and help relieve my concerns about the over the counter drug. A new formulation of purified EPA made by Amarin will hopefully be approved by the FDA in July .  My reasons for chosing Omega 3  fatty acids was simple. They worked and had less side effects. I was reluctant to use Tricor ( Fenofibrate ) because of the added risk  of myopathy and Niacins were just to difficult to tolerate.

The small percent
Their was a small percent of patients with  higher  LDL cholesterol and very high triglycerides  that did not respond to the above initial approach. This group requires a more aggressive approach and adjustment of the target goals.  These people have a higher risk from their disease than the risk of medicine side effects.

 Persistent elevation of triglycerides in the 800 to 1000mg/dl range increases the risk for pancreatitis.  In these patients , lowering the triglycerides to reduce the risk of pancreatitis is the initial goal. this may require combinations of medications including , Zetia ( ezetimibe ),Tricor( fenofibrates ) and Niacin.
 Achieving Triglycerides levels in the 200 to 300 range may be the best result they can do.

The person with a LDL Cholesterol of 190 mg/dl is not likely to achieve a target goal of 70 . They can expect and average LDL reduction of 38 mg/dl reduction with the initial Statin dose and about a 25 % reduction in the risk for heart disease. Each subsequent doubling of the Statin dose lowers LDL by about another 7 % ( the rule of 7 ) . Combination of other medications including some of the above and Questran ( cholestyramine ) may be needed.

Have fun Be smart Talk to your doctor about your treatment goals
David Calder, MD

 Tomorrow the new Omega 3 fatty acid waiting for FDA approval

Sunday, June 24, 2012

Diabetes, Residual Risk and Dysfunctional triglycerides

Diabetes, Dysfunctional Triglycerides and Residual risk
A lady  ,who is taking a statin , ask if she was completely protected from having a heart attack or stroke.
The answer is no.

Taking statin medications have been very effective at reducing  but not eliminating the risk of developing cardiovascular disease. This leaves some thing called Residual Risk.
This Residual risk is an area of active research and is focused on correcting low HDL cholesterol and/or elevated triglycerides levels. We have discussed low HDL previously and the problems associated with efforts to increase it.
See the June 4 , 2012 post

HDL Cholesterol - Is More Better ?

Please review the two previous post below and we will start discussing the hope of reducing Triglycerides and reducing the problem of Residual Risk.

Have fun , be Smart and improve your under standing of Triglycerides
David Calder,MD

*Elevated Triglyceride levels increase the risk of Stroke in postmenopausal
 women     April 12 , 2012

Dyslipidemia , especially elevated Total cholesterol ,LDL cholesterol  and decreased HDL, are well  established risk factors for the development of atherosclerotic heart disease .

They have not served as well as a marker of increased risk for ischemic stroke.

 However  medications such as Statins , which primarily lower LDL and total cholesterol , have demonstrated a significant reduction in stroke risk. This was well demonstrated in the CARDS study( lancet364(Aug.21,2004):685-696 ) which found a 48% reduction in stroke in patients with Type 2 diabetes taking 10 mg of atorvastatin ( lipitor).

I read an article this morning in the April issue of * STROKE that may help in our understanding of some of the risk factors for ischemic stroke in women. This article has a complicated title, Lipid and Lipoprotein Biomarkers and the Risk of Ischemic Stroke in Postmenopausal Women , and was  also not a quick easy read. This study was a prospective case study comparing 972 women with ischemic stroke to 972 matched control subjects.

Bottom line
  Elevated baseline triglyceride levels above the mean Triglyceride level of 140 mg/dl was a significant marker of increase risk of ischemic stroke in post menopausal women.

 Two other associated risk markers involve precursors to LDL cholesterol ;
  VLDL particle Size and IDL number,

Our liver produces VLDL ( very low density lipoprotein ) which is altered to IDL ( intermediate density lipoprotein ) and to the end product LDL( low density lipoprotein ) . Elevated triglyceride levels have an unfavorable effect on this process resulting in smaller more dense higher risk LDL particles.

 LIVER  produces ----------------> VLDL ------> IDL------> LDL
 Elevated Triglycerides effect- ->  size of             number of         smaller dense  higher risk LDL particles

     This article helps point the finger at elevated Triglyceride levels as being a risk factor for 
       stroke in postmenopausal women 

       It  also helps explain how elevated triglycerides effect the size and  and possible the 
       number of  LDL particles to increase someones increased risk for stroke and heart disease . 

       It also improves our understanding of the benefits of Statins , like lipitor and others , in 
       reducing stroke risk.

 Have fun, be smart and pay attention to your Triglyceride test results
 David Calder,MD


What is Non-HDL cholesterol ? Why should I care ?

We have discussed using LDL cholesterol and Apo b test  to help evaluate  our risk for developing heart disease. Today we are discussing another tool  that is gaining in popularity , Non-HDL Cholesterol .

 Non -HDL Cholesterol  is based on a simple idea . Elevated levels of any thing other than HDL is not in our best interest.

 Calculation is easy;
      Total cholesterol - HDL  =  Non - HDL Cholesterol

 Recommended  Target Goals by;    ADA ( American Diabetes association )
                                                          ACC ( American college of cardiology )

                              LDL            Apo b          Non-HDL cholesterol
                                mg/dl           mg/dl               mg/dl

no risk factors        <100            <90                 <130
+ 1 risk factor         <70             <80                 < 100

  risk factors include High Blood Pressure ,smoking , family history of premature heart disease.

  This is an easy test to do on your own lab.  and may help you and you physician make management decisions
                          Have  fun      Dr. Calder

Friday, June 22, 2012

Diabetes and Dysfunctional Triglycerides

Hypertriglyceridemia is recognized as a causal risk factor for cardiovascular disease. Elevated triglycerides drives a dysfunctional family of lipid problems that increase the risk for developing cardiovascular disease and contribute to the residual risk associated with Statin use. 

Elevated triglycerides also serve as a trigger for assessing other components of of the lipid profile such as non HDL-cholesterol ,Apo B , and small dense LDL measurements .

 I will review components  and treatment of hypertriglyceridemia over the next week and will start by asking you review some of my previous blogs on this subject.

 What is Apo-B ?                                                                                        May 10 2012

     Apo-b is an integral part of each LDL cholesterol particle made in the liver . LDL is responsible for carrying cholesterol to tissues in our body. Apo -b is the key opening the door to various cells in those tissues.

   LDL cholesterol  is the primary tool used to evaluate risk for heart disease. I have discussed some of the problems with LDL measurements in previous post. Dec,11,2011

 Basically LDL Cholesterol is produced in our liver in a spectrum of sizes, from small dense particles to large fatty particles. The size of the LDL particle is effected by Triglyceride levels . Triglyceride levels above  150 mg/dl is associated with an increase in small dense LDL putting a person at  higher risk of cardiovascular disease . 

I will ask you now to find your last lipid panel and do a little math.

 * calculate your LDL by subtracting your HDL and 1/5 of your triglycerides  from your total cholesterol

 * Now add  200 to your triglyceride test result and repeat the calculation. What effect did that have on your LDL cholesterol result ?
contact me at if you have a question

Have Fun , be Smart , do your math
David Calder,MD

May 11. 2012

A better way to evaluate LDL cholesterol

This is a follow up of yesterday post and request that you calculate your LDL cholesterol from your own test results.  My reason for asking you to do the math exercise was to put attention on the fickle nature of the LDL test result  used to evaluate our risk for Cardiovascular disease.

Some of the points to keep in mind are:
   * LDL is usually a calculated number
   * any increase in triglycerides results in a lower appearing LDL and a false sense  of security
   * any increase in triglycerides actually starting at about 100mg/dl is associated with an increase in small
      dense LDL and increased risk of cardiovascular disease.

Is there a better way of evaluating LDL cholesterol ?    Yes
  * Measuring  ApoB is the the easiest, least expensive most consistent way to evaluate LDL Cholesterol.
  * there is one ApoB for each LDL particle regardless of the LDL parcel size.

Treatment guidelines goals
  * American college of clinical endocrinologist ( AACE )
                                        ACCE  LIPID  and Athersclerosis Guidelines
                                        Endocr.Pract. 2012 ; 18 ( supplement 11: 1-78
          Apo B -    < 90 mg /dl in people at risk for cardiovascular disease
                           < 80 mg/dl for people with "established" cardiovascular disease 
                           < 80 mg/dl for patients with diabetes  plus one or more " risk factors "

  * American Diabetes Association  consensus statement on lipid management

          ApoB         < 90 mg/dl  - for people with diabetes  and no other risk factors
                                                - for people without diabetes without cardiovascular disease but with 2
                                                  "risk factors "
                             < 80 mg/dl  - people with "known" cardiovascular disease
                                                   people with diabetes plus one or more additional risk factors

   The official guidelines are catching up with what doctors have been doing for some time , using ApoB test to validate the the accuracy of LDL measurements in predicting risk for cardiovascular disease.

Who are those  "people at risk for cardiovascular disease " and what are those "risk factors" ?
 more tomorrow
Have Fun , Be smart and ask for an ApoB test with your next Lab. evaluation. You do not have to fast for this test.

David Calder, MD
email me at with questions or comments

THURSDAY, MAY 10, 2012

Have you checked your APO-b lately ?

Have fun Be smart look up your last Triglyceride  and LDL test results
David Calder, MD

Tuesday, June 19, 2012

Low -Dose Aspirin and Cancer mortality

Low- Dose aspirin and Cancer mortality: A Meta- Analysis of Randomized Trials
American Journal of Medicine June 2012 , 125 560-567

This study evaluated data from 11 trials reporting cancer mortality in patients taking low -dose aspirin
 ( 75 to 324 mg ). They compared cancer death among patients taking low dose aspirin and non aspirin users.
  Total number of patients -16,066                              
  cancer deaths in patients using aspirin- 162  of 7998 patients  ( 2.02% )
  cancer Deaths in non - aspirin users   -  210 of 8068 patients   ( 2.60 % )

Average followup 2.8 years

These studies demonstrate the effect of low dose aspirin for the prevention of cancer mortality can be realized over a  short  period of time.

They mention another study;
This study reviewed data from 8 different trials and found that aspirin reduced the long term risk of cancer mortality . The effect was observed after only 5 years of observation regardless of aspirin dose or type of cancer.
Rothwell P. et al  Effect of Daily aspirin on long term risk of death due to cancer
Lancet 2011; 377: 31-41

Have Fun , Be  Smart and talk to your doctor about the pros and cons of aspirin use
David Calder, MD

Monday, June 18, 2012

Fish Consumption and Colorectal Cancer

I will share a few articles from the June issue of The American Journal of medicine Volume 125 #6

Page 551                  Fish consumption and Colorectal cancer

 A few interesting points
   #1  there are over 1 million cases of colorectal cancer  diagnosed each year and 655,000 deaths each
         year world wide
   #2  Life style plays a role in the risk of having colorectal cancer , smoking , alcohol  consumption , 
         low intake of Vit B6 and diet in general . Dietary factors are estimated to contribute to about
         one  half of all colorectal cancer cases.
   #3  Studies done in Finland and Sweden suggest that higher fish consumption is associated with 
         lower risk of colorectal cancer . Other studies have fail to show a relationship  between fish 
         consumption and colon cancer
   #4  rectal tissue and colon tissue are derived from different embryonic tissue and may not respond the
         same even though they are connected.
  This article is a Meta analysis of 41 different studies and they concluded that fish consumption has 
  preventative effects on colorectal cancer . They were unable to determine  if the  kind of fish, how it
  was prepared or the amount was important.

    Have you had a colonoscopy done  ?
    Do you know what the current recommendations are ?

  Tomorrow . More on colon cancer 

Have fun , Be Smart  ask your doctor about having a colonoscope.
David calder,MD


Friday, June 15, 2012

LDL cholesterol and the Pre-Statin era

The pre- Statin era
 I have had the privilege of practicing medicine before before Statins became available . I can tell you , the treatment results were not that good and patients had problems tolerating the  available medications.

Bile acid resins( Questran and colestid ) had problems with causing gastrointestinal distress especially constipation , they interfered with the absorption of other medications and increased triglyceride levels.

Niacin was not well tolerated because of itching and flushing and an underlying concern of liver toxicity and increasing blood glucose levels at higher doses . Most of my patients never stayed on niacin for very long. The recent AIM-HIGH study did not help the niacin cause. This study, as I recall , was designed to demonstrate the benefits of using Niacin in reducing the residual risk of cardiovascular disease in patients with well controlled LDL of 70 mg/dl . Niacin failed to show any added benefit and the study was stopped early because of increased deaths in the treatment group. There are older studies combining Niacin with bile acid resins that were effective in reducing the risk of cardiovascular disease.

Fibric acids( Lopid [gemfibrozil] , Tricor [ fenofibrate] )  This class of drugs  are better tolerated and have been effective in reducing triglycerides and raising HDL . Combining this class of drugs with Statins does increase the risk of muscle problems and should be used with caution.

In general I would not want to go back to the pre-Statin era.

The chart below is a summery published in a good review article . I suggest reading the article for more details.

Have Fun, Be Smart and take advantage of the wonderful advances in medicine
David Calder,MD


From Journal of the American Pharmacists Association

New Guidelines for Managing Hypercholesterolemia

James M. McKenney
Posted: 07/01/2001; J Am Pharm Assoc. 2001;41(4) © 2001 American Pharmaceutical Association

Drug Class, Agents, and Daily DosesAverage Lipid/Lipoprotein EffectsAdverse EffectsContraindicationsClinical Trial Results
Bile acid resins[a]LDL-C ↓15%-30%
HDL-C ↑ 3%-5%
TG -- no change or increase
GI distress, constipation, decreased absorption of other drugsAbsolute:
G > 400 mg/dL
TG > 200 mg/dL
Reduced major
coronary events and CHD death
HMG-CoA reductase inhibitors (statins)[b]LDL-C ↓18%-55%
HDL-C ↑5%-15%
TG ↓7%-30%
Myopathy, increased liver enzymesAbsolute:
Active or chronic liver disease
Concomitant use with certain drugs[c]
Reduced major coronary events, CHD deaths, and total mortality
Nicotinic acid[d]LDL-C ↓5%-25%
HDL-C ↑15%-35%
TG ↓20%-50%
Flushing, hyperglycemia (or gout), upper GI distress, hepatotoxicityAbsolute:
Chronic liver disease
Severe gout
Reduced major coronary events, and possibly total mortality
Fibric acids[e]LDL-C ↓5%-20%
(may be increased in patients with high TG)
HDL-C ↑10%-20%
TG ↓10%-50%
Dyspepsia, gallstones, myopathyAbsolute:
Severe renal disease
Severe hepatic disease
Reduced major coronary events, increased non-CHD mortality (2 of 5 clinical trials)

Thursday, June 14, 2012

Statin safety- Your comment and mine " just give the facts "

Thanks for your comment.  I appreciate all the comments that I receive because they often lead to interesting and important discussions . I appreciate a comment from yesterday , " many health experts believe that statins only harm people "  , that I believe is incorrect and not backed up by the facts.

Documented Facts
Statin caused myopathy  , varying between mild and tolerable aches and pains to severe and intolerable, occurs in 1 person out of 10,000 taking a statin.  Rhabdomyolysis is rare and occurs in 0.15 per 1 million prescriptions written .

The primary cause of death for people with Diabetes is cardiovascular disease. A recent study reported in the June 2012 issue of Diabetes Care reported that 69% of diabetes deaths in the study had a cardiovascular cause listed on their death certificate .
Predictors of Mortality over 8 years in type 2 Diabetes   Diabetes Care  June 2012

The safety and benefits of Statins are well documented.  
I will review the data from a few of my favorite studies.

  The Heart Protection Study
This study demonstrated  substantial benefit to patients with Diabetes regardless of age or sex. Their conclusion was that taking 40 mg of simvastatin (Zocor ) daily would reduce their LDL cholesterol by 38.8 mg/dl and reduce their rates of developing heart attacks, strokes and heart revascularizations
by 25 %. Another way of looking at their data is, taking simvastatin daily for 5 years would prevent 55 people per 1000 from having a major vascular event.
* Heart Protection Study  Lancet 361 (June 14, 20013: 2005-2016

    CARDS study
This study involved 2838 patients with type 2 diabetes with no previous history of heart disease. The treatment group received 10 mg of atorvastatin (Lipitor ) daily and experienced significant benefit.
       Acute coronary events reduced by 36%
       Coronary revascularizations reduced by 31 %
       Strokes reduced by 48%
       Death rate reduced by 27%
       NO adverse events were reported in the treatment group. The placebo group had more complaints
       of muscle discomfort.
       Overall treatment with 10 mg of Atorvastatin (lipitor )would be expected to prevent 37 major
       vascular events per 1000 people treated for 4 years..
*Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin  Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.
Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH; CARDS investigators. Lancet 364 (August 21, 2004 ) 685-696

Tomorrows post - lowering cholesterol other options

Have fun , Be smart  and keep up your comments
David Calder,MD

Wednesday, June 13, 2012

Statins - alternate day dosing ?

Internal Medicine News  May 15, 2012
Alternate day dosing Mitigates Statin Muscle Pain  by Bruce Jancin
 (expert analysis from the annual meeting of the American college of physicians )

The author reviewed  2 articles using rosuvastatin ( Crestor ) but did point out that lipitor ( atorvastatin ) also has a long half life and would also work for alternate day use. The studies were all done on statin intolerant patients.
 #1  Alternate day Crestor 5 or 10 mg was studied in 51 patients .
       37 ( 73 % ) tolerated the regimen
       mean LDL lowering was 34.5 % half of them achieved their target LDL goal
            Ann. Pharmacology 2008;42: 341-6
#2   Once-weekly dose 2.5 to 20 mg was studied in 50 previously statin - intolerant patients
        base line LDL average 177mg/dl
       37 ( 74% ) tolerated the once weekly regimen
       The 5 mg group  lowered their LDL cholesterol by a mean of 75 mg/dl
        The 10 mg group lowered their mean  LDL cholesterol  by 79mg/dl
            clinical ther..2006;28: 933-42

   Alternate day doses is another option to consider for patients  who are intolerant to Statins.
Muscle problems associated with statins and any dose adjustments of medications need to be discussed and supervised by your physician.

Have fun Be smart ,  contact your physician if you have muscle complaints associated with Statins.
David Calder,MD

Monday, June 11, 2012

Statins -Getting more bang for your buck

Myopathy has been estimated to occur  in about 1 per 10,000 patients treated with statins . My own personal experience suggest that mild muscle aches and pains  related to statins is more frequent.

High dose = higher risk
Higher doses of Statins are associated with increased risk of muscle  and liver damage . The initial recommended dose gives the greatest reduction in LDL cholesterol , about a 27% reduction, subsequent doubling the dose results in an additional 7% reduction in LDL. This is called the rule of 7.
                                         American J. of Cardiology 1997;80:106-107
For example 2 commonly used Statins
                   zocor              Lipitor             LDL Cholesterol % reduction  
                  10 mg                5mg                   27% reduction in LDL
                  20 mg              10 mg                  34% reduction in LDL
                  40 mg              20 mg                  41% reduction in LDL
                  80mg               40 mg                  48% reduction in LDL
                                          80 mg                  55% reduction  in LDL

There is great individual variation in the effect of statins but general you get the most bang for your buck with the initial  starting dose , a 27% reduction in LDL cholesterol 
The subsequent 7% reduction attained with each doubling of the dose comes with an increasing the risk of muscle and liver damage.

There is another option .
Reduce your fat intake
Reduce the Fat intake in your diet by 25% and lower your LDL cholesterol by 5% without the    risk of muscle and liver damage
                                New Engl. J. Medicine 1993; 328: 1213-1219 Hunningshake DB et al
                                  the Efficacy of intensive diet therapy alone or combined with lovastatin

          "A reduction in  calories from fat from 40 to 20% , a 50 % reduction generally leads to approximately a 20 % reduction in LDL and total cholesterol"       
                                  Ornish D.  Can life style changes reverse coronary atherosclerosis ?  Hosp. Pract. 1991 ; 26: 123-132

Comment on food 
( little changes done over a long time work better than big changes done over a short time )

The Dean Ornish diet  , 10% fat  intake, mentioned above  was a little to difficult for most people to manage long term. However his studies were some of the first to demonstrate the power of lowering fat intake in managing and correcting  cholesterol problems.
Vegetarian diets some of recent ideas of the Mediterranean diet , Dash diet are a little easier to accomplish by gradually working them into our individual our life styles over time . You have plenty of time to make the changes , because managing cholesterol problems is a life time challenge and total reliance on a pill usually fails . See my comments on the Dash diet on May 19 post, The Dash diet my experience.

Have more fun
Spending you dollars on fruits, vegetables , whole grains and low fat dairy products is more fun than paying cardiologist and heart surgeons for their amazing skills.

The 5 % lowering of LDL cholesterol attained with a reduction in dietary fat intake is without risk  and is not much different than the 7% reduction attained by doubling the statin dose with higher risk of complications. The primary benefit gained from your  "Statin " is with the initial starting dose , a 27%  average reduction in the LDL cholesterol and then save time , you don't have to read food content labels , by shopping  in fruit and vegetable section of your grocery store.

Have fun , Be smart and eat your fruits and veggies
David Calder,MD

Saturday, June 9, 2012

Statins, Muscle pains ? What to do ?

Statin myopathy: A common dilemma not reflected in clinical trials
Cleveland Clinic Journal Of Medicine June2011 vol. 78 6 393-403

This is a  very good article that provides insight into the every day problem for doctors prescribing and patients taking Statins . 

" When a patient taking a statins complains of muscle aches, is he or she experiencing statin -induced myopathy or some other problem.? Should statin therapy be discontinued?"  

Muscle ache and pains are common in all of us and is estimated to occur in between 5  % to 20 % of people taking a statin. ( See yesterdays discussion for a list of Statin medications )
There is no specific test to diagnosis statin -induced myopathy. A blood test that measures  a muscle
breakdown product called CK ( creatine kinase)  can be measured and is used to help define the muscle problems better;
     Myalgia -              -  muscle weakness, tenderness ,aching, stiffiness with no elevation of CK
     Myositis               -  elevated CK  with muscle symptoms
     Rhabdomyolysis - severe muscle symptoms and CK 10 time the upper limit of normal

What to do ?
  The CK test may help but is usually normal and most of the time the patient and doctor are left to deal this problem. 

From the research data most patients make their decision and simply stop the medication
" 25% of adults who start taking statins stop them within 6 months , and up to 60 % stop by 2 years ".
Doctors have a more difficult decision because they are more aware of the significant benefits from taking Statins and generally feel that the benefits of treatment far outweigh the risk.

Other options

 # 1 Some statins have a higher frequency of muscle complaints
        * PRIMO Study
             Mild to moderate muscular symptoms with high dose statin therapy in hyperlipidemic patients 
            Cardiovasc Drugs Ther 2005; 19:403-414
           muscle related symptoms  varied with the statin regimen
             FlustatinXL       ( Lescol                  40 mg ----- 5.1%
             Pravaststin       ( Pravachol )          40 mg ----10.9 %
            Atorvastatin       (Lipitor )        40 to 80 mg ----14.9 %
            Simvastatin        (Zocor )        40 to 80 mg----18.2 %
            Rosuvastatin     ( Crestor )not included in this study

      *   Benefit - risk assessment of rosuvastatin 10 to 40 mg milligrams
                   American J. Cardiology 2003 Aug 21; 92 (4b): 23 K -29K
        This study reviewed 12,596 patients . They defined Myopathy as muscle symptoms and
        CK less than 1000. Myopathy attributed to Rosuvastatin occured in < 0.03 % and no cases
         of rhabdomyolysis were reported

comment : 
If you are having muscle symptoms that you believe are related to your medication ,Talk to your doctor. There may be  other options.

Tomorrow - Statins , Dose benefit and muscle symptoms, another option

 Have Fun , Be smart , Know your options
David Calder,MD

Friday, June 8, 2012

Muscle pains and "Statins"

Statin myopathy: A common dilemma not reflected in clinical trials
Cleveland Clinic Journal Of Medicine June2011 vol. 78 6 393-403

This is an interesting article pointing out that Statins are under prescribed because of concerns about muscle toxicity.

"25% of adults who start taking a statin stop taking them by 6 months, and up to 60 % stop by 2 years"

I was  not to surprised to learn that only 50 % of people who could benefit from taking a statin are on one. My own little observational study found that only 37% of 110  diabetes patients admitted to our hospital for coronary bypass surgery were taking a statin. I should point out that John Nelson, PA in our Diabetes Department did all of the work on our study.
( page 47  DIabetes Office Visit , My thoughts on Lipids , Statins, and Diabetes  )

Myalgia is common
Statin related muscle complaints are very common Myalgia is estimated to occur in 6 to 25 % of people taking statins. Accurate data is difficult to obtain because this symptom  is usually not reported.
Research studies report < 5% of patients have myalgia which is not to different from those taking a placebo.

 Rhabdomyolysis is rare
  0.15 deaths / 1 million prescription

  Rhabdomyolsis , is a  potentially life threatening condition resulting from the breakdown of muscle tissue. This is most commonly seen in crush injuries , alcohol abuse , muscle over exertion , heat stroke, genetic disorders, some medications including Statins. The combination of Statins with other lipid lowering medication such as fibrates , niacin and common medications such as erythromycin may increase the risk.
 The risk varies with different statins and seems to be dose related. Higher doses increase the risk. The percent of reported cases of Rhabdomyolysis as reported by the FDA
   Rhabdomyolysis             % cases reported              deaths per million prescriptions
   cerivastatin                           - 56.9%
   Simvastatin  ( Zocor )           - 18.3%                                   0.12 %
   atorvastatin  ( Lipitor )          - 11.5 %                                  0. 04%
   pravastatin  ( Pravachol )      -   7.3%                                   0. 04%
   lovastatin     ( Mevacor )       -   4.4 %                                  0. 19 %  
   fluvastatin    ( Leschol )         -   1.6 %                                  0.00%
   This study was done before rosuvastatin ( Crestor ) became available
Drug interactions
 It is always a good idea to check for drug interactions with any new medication you add to your treatment program. Your doctor , pharmacist and you can easily find this information

Early Symptoms
  Early symtoms of rhabdomyolysis  include dark tea colored urine , severe muscle pain  and weakness over the entire body . The tea colored urine may be your first clue. Stop the medication and contact your doctor immediately.
 Early diagnosis and treatment is very effective and full recovery can be expected.

Tomorrow- more on myalgia

Have Fun ,Be Smart and always contact your doctor before stopping your medication

David Calder,MD

Wednesday, June 6, 2012

Numb feet, lost keys and the OrthoWedge shoe

Numb feet require a little more attention
I was talking to a insulin pump group a few months ago and I showed them a number of items I found in peoples shoes over the years. My collection included toys, tooth picks,hair pins, nails, coins, rolled up socks and paper clips. 
One person in the group said that he has had neuropathy with numb feet for many years and had become  less careful with his daily foot care .
One day he lost his car keys and spent 2 to 3 days searching and finally found them , in his shoe.
He also found significant damage to the distal part of his foot. 

Eyes and hands have to replace the loss of pain sensation
The failure to recognize ongoing damage to numb feet or any other part of our body is not that uncommon.  One doctor , who spent years treating people with Leprosy  , felt that the lack of pain sensation essentially removes that part of the body from a persons general awareness and leads to neglect of the effected part. I believe he is probable right. Some patients are unaware of a large ulcer or enjury until they or someone else notices blood or pus on a sock or bed sheets. One older patient of mine was brought to my office by a friend who noticed blood and yellow material on his friends sock. I found  infection and embedded tooth pick in his big toe. I have had patients severely burn the soles of their feet setting by a campfire.

There are some general precautions for anyone with numb feet from any cause:
   * your eyes and hands have to replace your missing pain sensation . look at the bottom of your feet daily  
   * do not go barefooted even in the house
   * avoid heat on the effected area . A heating pad or  heated blanket can cause damage
   * shake out your shoes and put your hand in your shoe before putting it on

Our fellow with the lost keys continued
His doctor recommended , the Darco orthoWedge shoe and his enjury slowly healed.
This shoe helps relieve pressure on the damaged area.  Many foot injuries occur on the bottom distal part of the foot.This is also a favorite place for callouses and pressure ulcers to occur also.
These areas will not heal unless you remove pressure from the area. The shear forces on the wound are very high with any weight bearing and interferes with healing.

Over the years I found that the orthoWedge shoe by Darco or the use of a total contact cast worked very well in most cases . The shoe is easy to use and less expensive and is worth trying first. I generally kept a supply in my office.

Have Fun , Be Smart and check your feet
David Calder,MD

Monday, June 4, 2012

HDL Cholesterol - Is More Better ?

HDL cholesterol ( the good cholesterol )

HDL's Job
 One of HDL cholesterol's primary duties is remove LDL cholesterol ( The bad cholesterol ) from Inflammatory cells , called macrophages , in our arteries and move the LDL back to our liver for disposal.

More is better ?
Research over the years have shown that people with high HDL are better protected from the risk of heart disease than those of us with lower HDL levels. This has pushed physicians and patients to find ways of increasing HDL levels in us genetically less fortunate souls. Efforts to increase HDL levels  has not been met with any great success and in some cases seem to increase a person risk of an early exit.

Functional ability is better ?
The problems associated with increasing the amount of HDL  has increased interest in the idea that the functional ability of our HDL may be more important than the amount of HDL circulating around in our blood. This may be good news for those of us who always just a little below the recommended targets for HDL .

I have attached a copy of article from the New England journal of Medicine on this subject.
One defination that you may not be familiar with is Apo Lipoprotein A1.
Apo A1 is a major component of HDL and may contribute to the function of HDL.

Have Fun , Be Smart.   Lipids and Diabetes is a fascinating long term learning process
David calder,MD

Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

Amit V. Khera, M.D., Marina Cuchel, M.D., Ph.D., Margarita de la Llera-Moya, Ph.D., Amrith Rodrigues, M.S., Megan F. Burke, B.A., Kashif Jafri, B.A., Benjamin C. French, Ph.D., Julie A. Phillips, Ph.D., Megan L. Mucksavage, M.Sc., Robert L. Wilensky, M.D., Emile R. Mohler, M.D., George H. Rothblat, Ph.D., and Daniel J. Rader, M.D.
N Engl J Med 2011; 364:127-135January 13, 2011
Citing Articles (92)


High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden.


We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima–media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B–depleted serum from the study participants.


The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima–media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins.


Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima–media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.)