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Jun 12, 2011 0 comments Uncategorized Uncategorized

A major league thank you to board members and members of the NLA and President (now past) Michael Davidson who at the 2011 Annual Scientific Sessions bestowed on me  the President's Award (the highlight of my professional life). Also a thank you to my friend and colleague John West of Snellville, Georgia who so eloquently introduced me at the ceremony in Manhattan. In my acceptance speech I noted that I have travelled over two million frequent flyer miles in my lecture career which enabled me to influence an army of Lipidaholics and many others to get excited about lipidology. It was quite daunting and in reality ridiculous to be on the same stage as other NLA award winners Tony Gotto, Greg Brown and Rudolfo Paoletti (all of them Lipid Gods).  My journey into lipid education began in the mid 1980s and went nuclear in the early1990s and hit the road in 1998. Although so many contributed to my education I did specifically point out the following mentors:  Dan Rader, Frank Sacks, Sergio Fazio, Bob Rosenson, Virgil Brown, Michael Davidson, Jim Otvos, Bill Cromwell, Peter Jones (of Baylor) and Peter Toth. Time did not permit me to mention Harold Bays, Michael Miller, Pete Kwiterovich, Brian Brewer, Allan Sniderman and others. I extended great admiration to my "lipidaholic rat pack" of Greg Pokrywka, Barry Hull, John West and Tara Dall and because of a brain lock forgot to include my very dear friend Jamie Underberg. Although our relationship is just over a year old, I'd be remiss not to thank Tonya Mallory, Russ Warnick and Joe McConnell of Health Diagnostic labs who have rejuvenated me.  Of course I concluded with thanks to the most important folks in my life: my now departed and beloved Mother (Cora) and Father (Joseph), my so supporting and loving wife Phyllis and my real purpose for being on this planet, my son Bradford (much more famous than his father: just Google him). One other part of my speech deserves repeat: In reality the only reason I became a presence in Lipidology is because of the many thousands of folks who have attended my several thousand lectures in all 50 states. I remind all that none of that would have happened without the support of PhRMA. It is so easy to bash that industry but we would have virtually no understanding of lipid and lipoprotein physiology and pathophysiology CV therapeutics without their support of research and education. I have met with, learned from and worked with thousands of PhRMA people over the last decade. I mentioned two by name in my talk who have endlessly supported my mission to educate: Amrita Chari of Abbott Labs and Craig Sponseller of Kowa (apologies to the many others where time did not permit their mention like Deb Horn, Jason Powel, Ed Lord, Jim Foster, Brad Hardy and so many at BMS, Lilly, Merck & GSK).

As I celebrate my 65th birthday, I am so proud of my NLA membership, my Lipidology Certification and my Fellowship in the NLA.  Thank you all.

Tom Dayspring

KeywordsKeywords: president's service award 
Oct 12, 2010 0 comments Uncategorized Uncategorized

I have just returned from a trip to Buenos Aires, Argentina where I addressed the Argentina Lipid Society, an amazing group of over 500 members as well as the rather large 36th Congress of Argentina Cardiology. The talks centered on lipoprotein pathophysiology in patients with Triglyceride/HDL Axis disorders which, in common with the United States, they have no shortage of there.

 

The Argentina Lipid Society is very progressive, quite knowledgeable in lipids, and very interested in what NLA is doing internationally. They very much wish to participate in certification in Lipidology as well as being very interactive with the NLA.

 

Their current president is Dr Daniel Aimone (deaimone@hotmail.com

KeywordsKeywords:  
Apr 26, 2010 0 comments Uncategorized Uncategorized
Just released: Thiazolidinedione Drugs and Cardiovascular Risks A Science Advisory From the American Heart Association and American College of Cardiology Foundation Sanjay Kaul, MD, FAHA, FACC, Chair; Ann F. Bolger, MD, FAHA, FACC; David Herrington, MD, MHS, FAHA, FACC; Robert P. Giugliano, MD, ScM, FACC; Robert H. Eckel, MD, FAHA   Circulation. 2010;121:1868-1877. 
Keys to Patient Management

The following are keys to patient management:
• Identification and treatment of correctable risk factors
– Smoking cessation
– High-quality diet
– Weight control
– Exercise

• Use of established secondary prevention strategies
– Aspirin (or clopidogrel in patients intolerant of aspirin)
– Lipid lowering, with statins as the first-line therapy
– Blood pressure lowering

• Early and consistent attention to controlling hyperglycemia while avoiding hypoglycemia
– Metformin is generally first-line therapy, particularly in obese patients
– Thiazolidinediones should not be used with an expectation of benefit with respect to IHD events
– Insufficient data exist to support the choice of pioglitazone over rosiglitazone
– Thiazolidinediones increase the risk of heart failure and should not be initiated in patients with class III/IV CHF
KeywordsKeywords: diabetes tzds metformin 
Apr 26, 2010 0 comments Uncategorized Uncategorized

Please go over to the Lipid Geeks group under Groups URL and see my comments on a very inetersting case entitled "A case report of a diabetic woman with very low HDL-C."  You will learn something about HDL mapping but you will not miss the forest through the trees.

 

Tom D

KeywordsKeywords: hdl-c ldl-p diabetes 
Apr 23, 2010 0 comments Uncategorized Uncategorized

I got a tweet from a world famous lipidologist that I want to share:

 

"So, if particles = disease, but lipids no = particles, why the surprise that lipids no = disease?

 

Think about it! 

KeywordsKeywords:  
Apr 18, 2010 0 comments Uncategorized Uncategorized

How would you answer if asked how much do TG typically raise during pregnancy in normal women? The answer is 200-400%. How would you council a woman with serious TG elevations who wanted to be come pregnant?  Go over to the Groups page, click on the Lipidaholics Group and read case 256. I's appreciate any  comments.

 

Tom Dayspring

Apr 3, 2010 0 comments Uncategorized Uncategorized
Interesting case discussion where a rising LDL-C in a diabetic is of no concern. Go over to the Lipdaholics Groups page to see the case and add comments
KeywordsKeywords: ldl-p diabetes 
Mar 17, 2010 0 comments Uncategorized Uncategorized
The ACCORD Trial  (also go to my  Lipidaholics Group and see case 254 looking at an acutal patient) It is not arguable that elevated TG and increased TG-rich lipoproteins significantly increase CV risk. Often the high TG is associated with reductions in HDL-C (TG/HDL axis disorders) and of course since VLDL-C (TG/5) is always elevated, non-HDL-C is usually high. Indeed it is the ultimate NCEP ATP-III goal of therapy in patients with TG > 200 mg/dL.  Fibrates have a long history of monotherapy success in improving CVD outcomes. Please see the following for a very thorough discussion of the trials (Fibrate Therapy in Patients with Metabolic Syndrome and Diabetes Mellitus by myself and Gregory Pokrywka. Current Atherosclerosis Reports 2006, 8:356–364. What we needed is data on how would fenofibrate perform when added to a statin. That is what the Action to Control Cardiovascular Risk in Diabetes (ACCORD) is all about.  (NEJM 2010)  On face value (main conclusion) the trial seems to be null on the ability of fenofibrate to improve outcomes above what a statin can do in T2DM patients. We do have previous data with fibrates in diabetics or TG/HDL axis disorders. The DAIS (Diabetes Atherosclerosis Intervention Study Investigators) data (a very successful angiographic trial used fenofibrate monotherapy (with zero statin contamination) vs. placebo - Lancet 2001;357: 905–10)  was the first trial to show that fenofibrate delayed the onset or caused a disappearance of microalbuminuria (a microvascular endpoint). Of course since then we have had The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study trial theoretically looking at fenofibrate vs. placebo in T2DM patients (of course lots of statin drop ins occurred in the higher risk folks with abnormal lipids) and despite the overall null outcome, we got evidence that in metabolic syndrome patients with TG/HDL axis disorders (like the patient at hand) there was very significant benefit in those using fenofibrate (Diabetes Care 32:493–498, 2009). Although very few still use gemfibrozil (because of medicolegal reasons in a polypharmacy world) and no one in the US uses bezafibrate we know from the primary prevention trial Helsinki (gemfibrozil), and the BIP trial (bezafibrate) that the those fibrates were most successful in patients with elevated TG and low HDL-C. Glance at the following table from the ACCORD trial supplement data published in N Engl J Med 2010. DOI: 10.1056/NEJMoa1001282 (make no conclusions on ACCORD until you read the supplement).  The table shows that in patients with high TG and low HDL-C fibrates perform remarkably well in reducing clinical events- data from Helsinki, BIP Field and ACCORD are amazingly consistent is supporting that conclusion.  See ACCORD slides in the NLA slide URL. Despite the overall null finding, it sure looks like Fenofibrate duplicated the benefit seen in all of the other fibrate trials in patients with elevated TG and low HDL-C. I do not know of any other drugs, other than statins that have such an impressive record of helping our patients with TG/HDL-C axis disorders reduce adverse outcomes. Niacin would come closest using angiographic but no outcome data.  So what do I now advise, after ACCORD Lipid about future use of fenofibrate? In actuality, the trial actually reinforced a lot of what we previously knew and I believe supports continued aggressive care of high risk patients (with T2DM and/or metabolic syndromes) who have TG/HDL axis disorders (with a TG > 200 mg/dl) with statin/TG synthesis inhibitor use. TG synthesis inhibitor is a term I use to include fibrates/fibric acids, higher dose niacin (Niaspan) and very high dose N-3 fatty acid (Lovaza) therapy (all of those drugs do reduce TG beyond inhibiting FA and TG synthesis, but I find it a convenient description). If microalbuminuria is present then fenofibrate/fenofibric acid is the reasonable drug of choice to add on to the statin or statin/ezetimibe. As we all know in FIELD, there was also significantly less need for laser photocoagulation therapy of the retina and a significant reduction in neuropathic-related amputations of feet and toes (an off label use of fenofibrate that must be considered in real world lipid management).  Let’s look at the ACCORD Lipid trial in depth: 5518 patients with T2DM with TG< 700 or on-treatment TG < 400 and an abnormal HgbA1c (>7.5%)LDL-C < 180 mg/dL HDL-C < 55 for blacks and women  < 50 for all othersMean Follow-Up: 4.7 years  Mean Patient Age: 62 years  % Female: 31%Age: 40-79 years with clinical cardiovascular disease or age 55-79 years with subclinical cardiovascular disease or at least two additional cardiovascular risk factors  Endpoints:Combination of the primary outcome plus revascularization or hospitalization for heart failure Combination of a fatal coronary event, nonfatal myocardial infarction, or unstable angina Nonfatal myocardial infarction Nonfatal strokeAll cause deathCardiovascular deathHospitalization due to CHFThere were also prespecified subgroup endpoints including looking at those with the highest TG/HDL axis Baseline data in both treatment and placebo arms:    BMI ~32   Normotensive    TG ~ 162  (interquartile range 113-229)    HDL-C ~ 38    LDL-C ~ 100    Females  1/3 of cohort   Blacks 15%  Hispanics 7%    No lipoprotein concentration or non-HDL-C data released (mindboggling) 2765 assigned to receive fenofibrate plus simvastatin and 2753 assigned to receive placebo plus simvastatin (20-40 mg as need to normalize HDL-C). In some patients other drugs were needed to achieve LDL-C goal  (6%)  likely with ezetimibe.  The average simvastatin dose was only 22 mg.   There was ~ 80% compliance rate with study drugs and placebo  Mean LDL-C fell from 100.0 to 81.1 in the fenofibrate group & from 101.1 to 80.0 in placebo group
Mean HDL-C increased from 38.0 to 41.2 mg per deciliter in the fenofibrate group & from
38.2 to 40.5 mg per deciliter in the placebo group.
Median TG decreased from 189.0 to 147.0 in the fenofibrate group & from 186.2 to 170.0 in placebo group. Main Outcome: The annual rate of the primary outcome was 2.2% in the fenofibrate group, as compared with 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% CI  0.79 to 1.08; P = 0.32) Hazard ratios for the secondary outcomes, including the individual components of the primary outcome, ranged from 0.82 to 1.17 (P≥0.10 for all comparisons)
Annual rates of death from all causes were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P = 0.33     Finally we have a fibrate trial where no one can conjecture about increasing overall or CV mortality (even though such data was always null in all previous trials)
 In patients who had a TG level in the highest third (≥204) and an HDL-C level in the lowest third (≤34)  were compared with all the other patients (P = 0.057 for interaction). In patients with high TG levels and low HDL-C levels, the primary outcome rate was 12.4% in the fenofibrate group, versus 17.3% in the placebo group, whereas such rates were 10.1% in both study groups for all other patients.   The authors note: "Our subgroup results and those of these previous trials support the view that the addition of fenofibrate to a statin may benefit patients with type 2 diabetes who have substantial dyslipidemia. The use of combination fibrate–statin therapy in such patients is consistent with current guidelines that recommend treatment for patients with hypertriglyceridemia and low HDL cholesterol levels that persist despite statin therapy." So why the heck did they even study folks with TG < 200 mg/dL? There was indeed no lower limit for TG which would make a person ineligible for trial entry. The authors point out (in the supplemental paper available on line) that in reality only 15-20% of diabetics have TG > 200 mg/dL and finding > 5000 such patients would have been impossible. They correctly mention if they would have excluded patients with TG < 200 mg, we would have had a trial that only enlightened us on 20% of the diabetic population (that have TG > 200 mg/dL). We really needed to know what statin/feno would offer all T2 diabetics. The authors thought that the first trial looking at combination therapy had to look at the entire T2DM population. No one can argue with that. As a result of ACCORD, we now are a lot smarter. We now pretty much know with as much certainty as we will ever have, that in T2DM patients without elevated TG there is no clear indication to add a fibrate to a statin to reduce events. We can still add colesevelam, ezetimibe or Niaspan to get to goal in those patients with TG < 200. However, we now have additional data (supporting the findings of Helsinki, BIP and FIELD) that fenofibrate works best in those with TG > 200 mg/dL (see table above). If you did lipoprotein evaluations of those patients you would almost certainly find large VLDLs, VLDL remnants, CE-poor TG-rich large LDLs and lots of CE-poor small LDLs (all atherogenic particles contributing to apoB that usually do not respond well to statin monotherapy). Since the NCEP goal of therapy for patients with high TG is non-HDL-C, I wish they had analyzed that. There is no NMR analysis I am aware of from the study. It would be really interesting to see what happened to total HDL-P and HDL subspecies, which seemed to be so important in explaining the benefit of gemfibrozil in the VA-HIT trial.  World class experts (Frank Sachs, JC Fruchart, etc.) of the Residual Risk Reduction Initiative faculty (www.r3i.org web site) state the following (and if you are not regularly viewing this web site, please do so):  "The benefit of fenofibrate was only seen in the group of patients with atherogenic dyslipidemia, and none of the primary or secondary endpoints were statistically significant in the total study population which included many patients with LDL-C at goal and without combined atherogenic dyslipidemia. There is a risk that the positive and clinically important results seen in ACCORD Lipid will be lost in the context of ACCORD being seen as a ‘negative’ study. -----  ACCORD-Lipid shows that residual vascular risk can be safely and effectively addressed in patients with type 2 diabetes and atherogenic dyslipidemia. It is up to all of us to ensure that this message is communicated as effectively as possible to fellow physicians across the world as soon as possible." I also believe we got lots of other great info from this trial. There was more data on how safe fenofibrate and statin are. Virtually no toxicity. No venous thromboses or PE whatsoever as was seen in FIELD. No myositis over statin/placebo. No liver toxicity. No pancreatitis. No gallbladder toxicity, no cancers, etc. For whatever reason (and I offer no explanation) there seemed to be worse results in women (not adjusted for lipid quartiles). This is bizarre because In FIELD there was actually a trend towards more benefit in women than men. This is likely one of those unexplainable findings that occasionally show up when lots of data is analyzed.  So the Dayspring take home from ACCORD is:     In patients with cardiometabolic risk (high TG low HDL-C), especially those with T2DM the risk is high because of too many atherogenic lipoproteins (almost all explained by TG). Statin monotherapy helps, but residual risk remains unacceptable (the PROVE-IT trial showed if statins in ACS patients have the LDL-C < 70 but TG remains > 150, the residual risk is high). If on the statin or statin/ezetimibe (LDL receptor therapy) therapy the non-HDL-C remains high because the VLDL-C is high (remember VLDL-C is TG/5) then a fibrate add-on makes sense - so does high dose Niaspan or very high dose Lovaza (N-3 FA) but in diabetics the ACCORD results and the microalbumin benefit makes the fenofibrate an attractive as well as logical choice. 
Mar 1, 2010 7 comments Uncategorized Uncategorized

The data on President Obama was just forwarded to me by an NLA member. What would your advice, as a lipidologist, be to the President and his physician?     Here are the specifics:

 

2010 data: TG 46  HDL-C 62  LDL-C 138

CAC "negative"

Glucose normal   

 

In 2007:   TG 44   HDL-C 68  LDL-C 96   BP 105/62

 

Does the rise in LDL-C concern you?

 

For my thoughts please go over to Groups:  Lipid Geeks and see my posted reply. Please join our lipid geeks group and please post coments.

KeywordsKeywords: lipid testing 
Feb 26, 2010 0 comments Uncategorized Uncategorized
Go over to the Groups Section and click on Lipidaholics and check out the new  case discussion which illustrates some very important concepts, specifically understanding the core composition of LDL particles.
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Thomas Dayspring
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Job Title: Clinical Assistant Professor of Medicine; Director: North Jersey Institute of Menopausal Lipidology
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