Treat high triglycerides?

Opinion about treating triglycerides

Cardiovasc Diabetol. 2014 Dec 4;13(1):159. [Epub ahead of print]

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

Tenenbaum A, Klempfner R, Fisman EZ.

Abstract

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

5 years ago The Tubby Theory anticipated IMPROVE-IT positive result in 11-14

Update on Tubby Theory post IMPROVE-IT Trial

IMPROVE-IT trial affirms the validity of combination drug therapy in this positive trial with Vytorin.  A pill that has both simvastatin and ezetimibe (Zetia).

I wrote about Zetia 5 years ago in my book, The Tubby Theory of Topeka. 

IMPROVE-IT affirms the advice of combination drug therapy that I gave in 2010. 

Zetia plus statin is now evidence based. 

This clears the way for Niacin in combination with statin in patients unable to afford Vytorin or Zetia. 

At low dose 1,000 mg Endur-acin (wax matrix niacin) is very safe. 

Safety concerns about Niacin are misplaced, I believe, as written in Laropiprant is the bad one

The Statin multiplier effect if started earlier and used longer

Today while writing a critique of a  
Dr. Uffe Pavnskov link article 
and using quotes from
1- Dr. Allan Sniderman et. al.   link
2- NLA point counterpoint article, link

 I coined a term called the
Multiplier effect of statins if used earlier and longer.

The Multiplier Effect of Statins if used early and longer

More Validation of Tubby Theory from 2009

First  see Dr. Sniderman on early treatment of risk

 Second article below

Curing Atherosclerosis

 Should Be the Next Major Cardiovascular Prevention Goal

   

Jennifer G. Robinson, MD, MPH,* Samuel S. Gidding, MDyz

                       

Iowa City, Iowa; Wilmington, Delaware; and Philadelphia, Penn

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in developed and developing countries. Despite decades of effort, unhealthy lifestyle habits and ASCVD risk factor levels remain high and are increasing in many population groups.

A new approach to ASCVD prevention is needed.

Multiple lines of evidence from animal and human studies suggest that atherosclerosis regression and normalization of vessel function can occur when low-density lipoprotein cholesterol (LDL-C) lowering occurs early in the course of atherosclerosis or when very aggressive LDL-C lowering occurs somewhat later.

We propose a new paradigm focused on curing atherosclerosis early in the course of the disease.

An approach that resets the vascular aging clock composed of initial regression therapy followed by periodic retreatment to suppress atherosclerosis development may be possible, with the ultimate goal of preventing subsequent ASCVD events.

Proof-of-concept studies are needed to determine:

1) the optimal age and/or extent of atherosclerosis for intervention and LDL-C–lowering therapy;

2) the intensity and duration of therapy for inducing atherosclerosis regression; and

3) documenting the normalization of vascular function. Ultimately, this new paradigm will need to be evaluated in ASCVD outcomes trials. 

(J Am Coll Cardiol 2014;63:2779–85) a 2014 by the American College of Cardiology Foundation

                   

               

           

           

                           

       

   

Number Needed to Treat for Mediterranean diet

NNTT or number needed to treat before one person benefits from a strict Mediterranean diet after 5 years is 61.  Found on:

 https://www.youtube.co/watch?v=eHxaDQNyfV4

The Battle of the Diets: Is Anyone Winning (At Losing?)

Paradigm Change in Fatty Acid science

Paradigm Change in Fatty Acid science

http://www.ncbi.nlm.nih.gov/pubmed/22658146#

J Clin Lipidol. 2012 May-Jun;6(3):216-34. doi: 10.1016/j.jacl.2012.04.077. Epub 2012 Apr 13.

Fatty acids in cardiovascular health and disease: a comprehensive update.

Baum SJ, Kris-Etherton PM, Willett WC, Lichtenstein AH, Rudel LL, Maki KC, Whelan J, Ramsden CE, Block RC.

Source

Miller School of Medicine, University of Miami, Miami, FL 33136, USA. sjbaum@fpim.org

Abstract

Research dating back to the 1950s reported an association between the consumption of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, however, challenges these findings. It is well accepted that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA intake. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in addition to decreasing HDL-C, it also increases triglyceride and LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new evidence that is questioning the health benefits of even MUFAs and PUFAs. In addition, in a few recent studies investigators have also failed to demonstrate expected cardiovascular benefits of marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association held a fatty acid symposium at the 2011 National Lipid Association Scientific Sessions. During these sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk was reviewed.


 More articles:


1- 4-Mozaffarian D et al. PLoS med 201023: 7 e10000252 Meta-Analysis of Randomized Controlled Trials- Displacing with PUFA, Carbohydate, MUFA
2- Am J Clin Nutr. 2010 Mar;91(3):502-9. Epub 2010 Jan 20.
Saturated fat, carbohydrate, and cardiovascular disease.
Siri-Tarino PW, Sun Q, Hu FB, Krauss RM.
3-Cochrane Database Update
WITHDRAWN: Advice on low-fat diets for obesity.
Summerbell CD, Cameron C, Glasziou PP.
4-Regular egg consumption does not increase the risk of stroke and cardiovascular diseases.Qureshi AI, Suri FK, Ahmed S, Nasar A, Divani AA, Kirmani JF.5-Epub 2011 Jan 26.
Astrup A Dyerberg J, Elwood P, Hermansen K, Hu FB, Jakobsen MU, Kok FJ, Krauss RM, Lecerf JM, LeGrand P, Nestel P, Risérus U, Sanders T, Sinclair A, Stender S, Tholstrup T, Willett WC.
The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?
"Furthermore, the effect of particular foods on CHD cannot be predicted solely by their content of total SFAs because individual SFAs may have different cardiovascular effects and major SFA food sources contain other constituents that could influence CHD risk."
6-Epub 2010 Jan 20.
Saturated fat, carbohydrate, and cardiovascular disease.
Siri-Tarino PW, Sun Q, Hu FB, Krauss RM.
"An independent association of saturated fat intake with CVD risk has not been consistently shown in prospective epidemiologic studies, although some have provided evidence of an increased risk in young individuals and in women."
7-Epub 2010 Mar 31.
Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence.
Micha R, Mozaffarian D.
"Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid."
"Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects,"

Niacin in AIM HIGH subgroup

Still hope for Niacin with high TG and low HDLc

AIM HIGH highlight:

“Niacin treatment was not associated with benefit or harm in tertiles of baseline lipids except for

a possible benefit in the high TG/low HDL-C subgroup.”

Relationship of Lipoproteins to CV Events: The AIM-HIGH Trial

Salim S. Virani, MD, F.A.C.C. (Disclosure)

August 04, 2014

Dr. Daysprings lesson on lipids shown here

Understanding the Entire Lipid profile Thomas Dayspring MD, FACP
There is only one absolute in atherosclerosis: sterols (predominantly cholesterol) entering the artery wall and being internalized by macrophages, creating foam cells (the histologic diagnostic marker of atherosclerosis) and the associated inflammatory process. If one can keep sterols out of the intimal layer there cannot be atherosclerosis. Sterols, other than cholesterol are termed noncholesterol sterols (sitosterol, campesterol, stigmasterol and many others). Some term these phytosterols but not all are of plant origin.
Since lipids (sterols, phospholipids and triacylglycerols or triglycerides) are oils (hydrophobic) they are transported in plasma in protein wrapped vehicles called lipoproteins. The surface proteins which convey solubility and structure to lipoproteins are called apoproteins or apolipoproteins. Thus, the only way sterols get into the artery wall is as passengers in the lipoprotein particles transporting or trafficking them. The particles are driven into the arterial intima by concentration gradients. Quantitating atherogenic lipoproteins is the best determinant of CV risk and thus particle concentrations are not only the best way to predict risk, but are also the best goals of therapy. Historically, for a variety of logistic reasons, few clinicians have performed lipoprotein testing. But this is changing and in April 2008, the ADA and ACC issued a consensus statement on LipoProtein Management mandating particle quantification in patients with moderate, high or very high risk; if you are basing CV risk and goals of therapy using lipid profiles, you are simply using lipid concentrations as surrogates or proxies of lipoprotein concentrations. You are guessing! Previously we have assumed that if LDL-C is elevated LDL-P (LDL particle concentration) is also elevated. Unfortunately, in an insulin resistant world, where small LDL particles predominate, that is not always true and very often the least useful surrogate of LDL-P is LDL-C! In these patients there is a major disconnect between LDL cholesterol and LDL particle concentrations. Lipid profiles report lipid concentrations: how much cholesterol is within all of the LDL, HDL or VLDL particles that exist in a deciliter of plasma. Never confuse LDL- C or HDL-C with LDL-OP or HDL-P.
Before we get to understanding the lipid profile, a few lipoprotein basics. Lipoproteins can be separated in the lab using several techniques such as:
1) Ultracentrifugation: (VAP)
2) Surface apolipoprotein content (apoB, apoA-I and others) using antibodies
Beta-lipoproteins: apoB is on chylomicrons, VLDLs, IDLs, LDLs, remnants, Lp(a)
Alpha-lipoproteins: apoA-I is on HDLs
3) Electrophoretic mobility: (beta, alpha) (Berkeley)
4) Surface charge (used predominantly for HDL: prebeta 1 &2) and alpha (1,2,3)
5) NMR or Nuclear magnetic resonance spectroscopy: (VLDLs, LDLs, IDLs and HDLs)
Depending on the technique used, the apoB (historically called beta) and apoA-I (historically called alpha) particles can be grouped into subparticles based on size or the presence of other apolipoproteins. The terminology can be complex and confusing, as there is no standard.
To keep it simple, the apoB-containing lipoproteins are the potentially atherogenic particles and apoA-I particles are the presumed non-atherogenic particles (HDLs). ApoB (a collective measurement of how many chylomicrons, VLDLs, IDLs, LDLs and Lp(a) particles are in plasma, measurement of apoB has long been recognized as a far superior predictor of CHD events than are any lipid concentrations including LDL-C. In several major studies elevations of the apoB/ApoA-I ratio has proved to be the best marker of CHD risk: such patients have too many atherogenic and too few non-atherogenic particles.
If an apoB particle enters the vessel wall, the apoB moiety attaches (fixes) to arterial wall proteoglycans and the surface phospholipids are subject to modification by reactive oxygen species, and the proteins by glycation from glucose, etc. The oxidized phospholipids are subject to further lipolysis by an enzyme called lipoprotein associated phospholipase A2 (Lp-PLA2), the hydrolytic products of which (oxidized fatty acids and lysophosphatidyl choline) create endothelial dysfunction and recruitment of macrophages. The modified or oxidized particles are then

Understanding the Entire Lipid profile Thomas Dayspring MD, FACP
internalized by macrophage scavenger receptors and CD36, 40, etc. The factors that determine whether a lipoprotein will invade the intimal layer are 1) concentration, 2) size < 70 nm and endothelial integrity. LDL particles have a diameter in the range of 18-23 nm. Of these measurements (particle concentration and particle size), only particle concentration is statistically significantly related to atherosclerosis and clinical events. Particle size is important, but by itself has no statistical independency in any study (where both LDL-P and LDL-size were both measured) to predict events. Concentration of lipoproteins is referred to as quantity and lipoprotein size as quality. No one should be making diagnoses or risk assessment or judging therapy by looking only at lipoprotein sizes! In reality if you have concentration data, particle size is not that important. Put another way without concentration data, particle size cannot help you.
Real world clinicians have two ways of quantitating lipoproteins: 1) apoB and apoA-I or 2) the NMR LipoProfile (www.lipoprofile.com) offered by LipoScience which provides VLDL-P, IDL-P, LDL-P and HDL-P. Since there is one apoB protein on every beta-lipoprotein, apoB is a collective measurement all of the apoB particles in a deciliter (dL or 100 cc) of plasma. Because of their long half life, 85-90% of apoB represents LDL particles. ApoA-I is an estimate of HDL particle concentration. However, each HDL particle usually has 2 to 4 apoA-I proteins, so the relationship between apoA-I and HDL-P is not as exact as apoB is with beta-lipoprotein concentrations. The NMR LipoProfile reports individual concentrations of each of the apoB (VLDL, IDL and LDL) and apoA-I (HDL) subparticles in umol/L or nmol/L. The NMR LipoProfile does not report apoB or apoA-I levels, as there is no need for them with the NMR reporting individual particle concentrations. Note that the NMR HDL-P contains only alpha-HDL numbers (small and large or HDL2 and HDL3). Free (unlipidated) apoA-I or prebeta (nascent) HDLs (5% of total HDL-P) are not captured by NMR technology.
Most clinicians order lipid profiles which as mentioned report lipid, not lipoprotein
concentrations. The educated provider then uses the various lipid concentrations as surrogates or proxies of apolipoprotein B and A-I (particle concentrations) and as proxies of lipoprotein particle sizes. In order to make everyone as expert as possible, here are tips to help you get the most value from a lipid profile.
First recognize that only Total Cholesterol (TC) and HDL-C are actual lab assays. VLDL-C and LDL-C are calculated using the TG level (that is why lipid profiles should be done fasting).
TC = HDL-C + LDL-C + VLDL-C + IDL-C + Chylomicron-C + Lp(a)-C + Remnant-C
Keep in mind: under normal circumstances, when fasting, there are no chylomicrons, remnants (smaller chylomicrons or VLDL particles) or very many if any IDL particles (these are postprandial lipoproteins):
TG is the triacylglycerol concentration within ALL of the TG-trafficking lipoproteins in 100 cc or a dL of plasma
TC is the cholesterol content of every lipoprotein in a deciliter of plasma
LDL-C is the cholesterol content of all the IDL and LDL particles in a dL of plasma HDL-C is the cholesterol content of all of the HDL particles in a dL of plasma VLDL-C is the cholesterol content of all of the VLDL particles in a dL of plasma
Remnant-C is the cholesterol content of all of the remnants in a dL of plasma
(Note NCEP recommends using VLDL-C as your surrogate of remnant-C) Lp(a)-C is the cholesterol content of LDL particles that have apo(a) attached Lp(a) concentration is the concentration of apo(a) in 100 cc of plasma
LDL-P is the number of LDL particles in a liter of plasma (expressed in nmol/L): this represents all sized LDL particles: large, intermediate or small
HDL-P is the number of HDL particles in a liter of plasma (umol/L) VLDL-P is the number of VLDL particles in a liter of plasma (nmol/L)

Understanding the Entire Lipid profile Thomas Dayspring MD, FACP
Labs like LipoScience break particle concentrations down even further:
Total LDL-P is the sum of all of the LDLs in a liter of plasma
Small LDL-P is the number of small and intermediate LDL particles per liter of plasma
They also report particle concentrations for all of the IDL, HDL and VLDL subparticles with actual molar concentrations.
Of course when labs report calculated or direct LDL-C to you, it is really LDL-C + IDL-C, as labs cannot separate IDLs from LDLs (without significant expense). Remnants are smaller, cholesterol-enriched VLDLs and chylomicrons. In fasting states chylomicrons and IDLs and remnants should not even exist to any appreciable extent. Most people do not have significant quantities of Lp(a), so in effect in most patients:
TC = HDL-C + LDL-C + VLDL-C
HDL particles are apoA-I particles and LDL and VLDL (plus all of the others mentioned above) are apoB particles, so in reality TC is the sum of the cholesterol in all apoA-I and apoB particles. :
TC = apoA-I-C + apoB-C
It is conventional to refer to the cholesterol in the apoB particles as Non HDL-cholesterol or Non HDL-C. Simply put, apoB-C is the cholesterol that is not in the HDL particles. In fact since apoB particles are the potentially atherogenic particles, Non HDL-C is our best surrogate (in the lipid profile) of apoB or potentially atherogenic particles.
In almost all circumstances the majority of the apoB particles are LDLs. Chylomicrons, VLDLs, IDLs, remnants have half life's of minutes to 4-6 hours, LDL particles have half life's of 2-3 days. Thus under most circumstances, ~90% of an apoB level represents LDL particles.
NCEP uses TC and especially LDL-C as its apoB surrogate and Non HDL-C as its surrogate when hypertriglyceridemia is present (at a level > 200 mg/dL). The reason being is that when TG levels are elevated there is apt to be delayed catabolism (lipolysis) of TG-rich, apoB lipoproteins (VLDL, Chylomicrons, IDLs, remnants). My personal belief, supported in the literature, is that Non HDL-C is a better surrogate of apoB than is LDL-C at any TG > 70 mg/dL (for sure, when TG are > 100-130). By the time a TG is 200 mg/dL, most people are drowning in apoB particles.
In summary the apoB surrogates you should be using are
1) TC (unless HDL-C is very high) 2) LDL-C
3) Non HDL-C
4) TG or VLDL-C
How about apoA-I? This is easy: Your only surrogate of apoA-I in the lipid profile is the HDL-C concentration. However some caution is needed. On the apoB particles, there is one apoB per lipoprotein particle. HDL particles can contain several (typically 1-4) apoA-I proteins. Thus the relationship between apoB and apoB particles is more linear that is apoA-I to HDL-P relationship.
Please note that if TG are perfect (<70-100 mg/dL), for all intents and purposes Non HDL-C and LDL-C are one in the same as a surrogate of apoB and there is no major advantage of Non HDL- C calculations over LDL-C. However, in America, how many patients have TG < 70-100 mg/dL? Yet why not always use Non HDL-C, instead of LDL-C as the apoB surrogate (as long as the TG <500 mg/dL). At TG> 500 mg/dL there is no good surrogate of apoB other than TC: reason ---

Understanding the Entire Lipid profile Thomas Dayspring MD, FACP
when TG are grossly elevated, one may have few but very large VLDL or chylomicrons which of course grossly elevate the TG level, but not the apoB level.
How about guessing or estimating lipoprotein particle sizes? There are many clues in the lipid profile. But first a word about particle sizes.
The major driving force with respect to apoB particles entering the arterial intima is particle number (especially LDL-P) and of course endothelial function. A particle larger than 70 nm will not enter the artery wall (the very large VLDL subparticles and Chylomicrons). Smaller VLDLs and chylomicrons (remnants), IDLs and of course LDLs easily enter the intima if present in increased concentrations. Since LDLs are the most numerous apoB particle present in plasma (due to their half life), it is obvious that LDL particles (small and large) are in most patients, the most atherogenic particles that exist.
With respect to HDL particles, size does not really matter. HDL particles of any size are so small that they can easily enter an artery wall. Of course, HDL particles are in a constant state of dynamic flux (remodeling). Little particles lipidate (become large) and then delipidate (become small). We really have no way of determining HDL functionality (ability to perform lipidation or delipidation, peripheral cholesterol transport or numerous other non-lipid antiatherogenic functions). Neither HDL-C, apoA-I or HDL-P or HDL size seem to be related to HDL particle functionality. One needs HDL particles of all sizes and they must be capable of rapidly changing.
Let's look at the atherogenic apoB particles and see what in the lipid profile indicates LDL particles are likely small:
Small LDL particles:
1) Low HDL-C
2) TG > 130-150
3) TC/HDL-C ratio > 4.0
4) TG/HDL-C ratio > 3.8 in women or 4.0 in men 5) Unremarkable LDL-C, but elevated non HDL-C
Remnant lipoproteins (smaller cholesterol-laden VLDL and chylomicrons)
1) TG > 150- 200
2) Elevated VLDL-C > 30
3) Unremarkable LDL-C with an elevated Non HDL-C 4) Low HDL-C in insulin resistant patients
5) Elevated TC/HDL-C ratio and TG elevation (>150)
Large VLDL particles which convey risk through rheologic, multiple coagulation and inflammatory associations and their role in creating atherogenic remnants, small LDL and small HDL particles (which are then excreted in the urine, causing a reduced concentration of HDL particles)
1) TG > 150-200 and/or VLDL-C > 30
2) Postprandial hypertriglyceridemia (> 170-200)
3) Decreased HDL-C
4) Elevated TC/HDL-C ratio and TG elevation (>150)
If you were paying strict attention you have noticed that low HDL-C is almost always associated with abnormal apoB particles (especially if insulin resistance is present): small LDL, remnant particles and large VLDL. Indeed, low HDL-C may simply be an epi-phenomenon alerting you to all of those atherogenic apoB particles. This is a crucial point and it is why treatment in low HDL- C states should always be directed first at apoB (LDL-C, VLDL-C or non HDL-C), rather than

Understanding the Entire Lipid profile Thomas Dayspring MD, FACP
apoA-I or HDL-C. In summary, especially in insulin resistant patients, with unusual exceptions low HDL-C means elevated apoB.
SUMMARY: To read a lipid profile properly and effectively:
1) Look at the TG: If > 500 treatment is needed and the TG takes precedence over all other lipid concentrations. If TG are less than 500, go to step (2)
2) Look at the LDL-C, because if it is above 190 mg/dL, drug therapy is indicated no matter what else you find. At lesser levels it depends on the risk of the patient whether drug treatment is indicated.
3) Look at the HDL-C: concern if < 40 male or 50 woman 4) Calculate the TC/HDL-C ratio: Concern if > 4.0
Some advocate LDL-C/HDL-C ratio, but I do not since LDL-C is a calculated value
5) Calculate the non HDL-C (TC minus HDL-C). NCEP says to do this only if TG are > 200, but
in reality this calculation is always equal to or better than LDL-C (less valuable if TG >500) 6) Calculate the TG/HDL-C ratio
7) If apoB/apoA-I ratio is so predictive (and it is): you can estimate it by looking at
TC/HDL-C or Non HDL-C/HDL-C
All should know that the NCEP goal for Non HDL-C is 30 mg/dL higher than whatever the LDL- C goal is for a given patient. Thus if your LDL-C goal is 70 (very high risk patient), the Non HDL-C goal would be 70 + 30 or 100 mg/dL. In a primary prevention setting where NCEP calls for an LDL-C of 130, the non HDL-C goal is 160. I agree with the AHA Women's Guidelines: all adults should have a non HDL-C < 130 mg/dL.
Interesting note: The Canadian Lipid Guidelines call for normalization of both LDL-C and then the TC/HDL-C ratio (make it < 4.0).
Example: If you ignore a very high risk person with an LDL-C of <70 but who has a TC/HDL-C ratio > 4.0 you have not achieved goals. Obviously there are still apoB particles present! Additional therapy is warranted.
NCEP uses the TC/HDL-C as a powerful risk predictor, but as a goal of therapy wants us to use LDL-C and then Non HDL-C.
Example: If you ignore a very high risk person with an LDL-C of <70 but who has a Non HDL-C > 100 mg/dL and the TG are still elevated (>200) you have not achieved goals. Additional therapy is warranted.
In closing, the lipid profile provides a significant amount of information on what lipoproteins might be present or absent. Tragically far too many clinicians are too focused on LDL-C and do not use the rest of the profile. That shortcoming is a big reason why patients are so under treated in the US. If you truly understand all I have written you will also rapidly appreciate how necessary combination lipid therapy is. Keep in mind that NCEP calls for combo therapy, when monotherapy fails to achieve either LDL-C or Non HDL-C goal.

2014 update on Tubby Theory

you tube 6 min 40 sec video on Tubby theory update 2014


17 slides 0n 2014 update of Tubby theory

Why do guidelines insist on telling us what is healthy food when there is a sea change in data?

This blog is my response to Dr. Seth Baum’s blog at Policing food

Until we know which genome should eat which diet, I think Dr. Baum’s quote should be at the beginning of every diet guideline.

” In short I’m fairly certain we are all quite different, and consequently do better with different diets.” Dr. Baum

Instead the lifestyle guidelines bury this uncertainty in this statement:

“It also recognized that RCTs examining the effects on hard outcomes (myocardial infarction, stroke, HF, and CVD related death)are difficult if not impossible for a number of reasons (e.g., long-term adherence to dietary changes).”

Hard data hard to come by with diet studies

The history of McGovern guidelines is very educational at:

https://docs.google.com/document/d/1oiVwyhEafkeegj8EQFlf5fJrIIZ1vWJX4Vt671HIBzk/edit

Most interesting is this statement in the report above:

“The Departments made relatively few changes from the first edition,

but this second edition was issued with much less debate from either industry or the scientific community.

The 1985 Dietary Guidelines were widely accepted and were used as the framework for consumer nutrition education messages. They also were used as a guide for healthy diets by scientific, consumer, and industry groups.”

McGoverns guidelines were very controversial when they came out in 1977. What happened in 1985 that there was little controversy?

Documentaries such as

1- FED UP 2014 and

2-The Men Who Made Us Fat 2012

put forth some theories.

This Atlantic article explains that McGovern had poor data about the eating habits of early Americans who did not have heart attacks.

https://docs.google.com/document/d/1_sHNfG2mRqXhXC8RarsobsBjChGq-b14Col_6MaoQIw/edit#heading=h.rmcfb15z4k9o

I am disappointed to see the latest 2013  Lifestyle guidelines  miss these important articles:

https://docs.google.com/document/d/1lZsNzOiiX_gFadx114u1o2NGJmES0ehx1Nu1kvzScsg/edit

Unfortunately when Chief Scientist, Dr. Rose Marie Robertson,  of guidelines uses the term “LDL levels” instead of the guidelines suggested metric of non-HDL cholesterol we can see the problem.

High fat diets raise HDL-C.

Subtract HDL-C from Total Cholesterol and you have a better number than the LDL-C most old trials used.

Dr. Rose Marie Robertson writes: “The link between saturated and trans fat intake and LDL cholesterol levels is irrefutable, as is the link between LDL levels and coronary artery disease”

This very strong statement is too simple.

Trans fat acids are bad but grouping all fatty acids in one group is wrong as Micha article demonstrates:

“Compared with carbohydrate, the TC:HDL-C ratio is

1- non-significantly affected by consumption of myristic or palmitic acid,

2-is non-significantly decreased by stearic acid, and

3-is significantly decreased by lauric acid.”

“LDL levels” is an inexact term and

the new ACA/AHA guidelines directs us to use

non-HDL cholesterol levels as a better predictor of risk.

I believe LDL particle numbers are even better and most the literature of the past does not take non-HDL cholesterol or LDL particle numbers into account.

This is a very critical point as high fat diets raise HDL-C and thus the non-HDL cholesterol number is better than the LDL-C number.

Another reference from Lipid journal article states:

“ Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles

(in addition to decreasing HDL-C,

it also increases triglyceride and LDL particle concentrations).

Thus Dr. Robertson”s statement:

“The link between saturated and trans fat intake and LDL cholesterol levels is irrefutable”.

This statement demonstrates that such certainty can not be used when imprecise and antiquated lipid terms are used.

I will end with Dr. Seth Baum’s final paragraph:

“I will emphasize one point however, and of this I am sure. No one knows what diet is best for all mankind. And until such a discovery is made, creating a food police force is probably not a good idea at all.” Dr. Baum

6.5 minute video on why you can't maintain weight loss and what to do about it

Why you can't maintain weight loss link


A normal person has 40 billion fat cells.

An obese person has 120 billion fat cells. 

A reduced obese person has 120 billion shrunken fat cells. 

Those shrunken fat cells are the SPONGE to soak up calories and why you can't maintain weight loss. 

I call it the Sponge Syndrome of the Reduced Obese.

My recent writtings 2014

My Commentary on Lecture Pad link

Commentary by Brian Edwards, MD regarding the manuscript: Diets to Prevent Coronary Heart Disease 1957- 2013: What Have We Learned?By James E. Dalen, MD, MPH and Stephen Devries, MD, FACC from the American Journal of Medicine

You have to register on Lecture Pad to read article or you can read it on my documents: https://docs.google.com/document/d/1u6OtjPONyBVmlB1mXVsRSdwWKpTnZTuWcF31TyI3W50/edit


I review 3 articles by Yale Professor Katz 

Why people can't maintain weight loss

http://t.co/fQNDNVXe

Watch the 1 min 40 sec video below to understand why people who have lost weight almost always gain it back. 

  Dr. Rudolph Leibel and Dr. Michael Rosenbaum, have been researching the effects of the hormone leptin on weight maintenance.

Giants of Obesity Reseach

Glycemic index- Brazilian bean study

Market in Belum, Brazil
(Am. J Clin Nutr 2007; 86(3): 707-13. This was an eighteen-month randomized trial of a low-glycemic index diet and weight change in Brazilian women. Two hundred eight women were on two diets with 41-point difference in glycemic index. They did not have a significant difference in weight loss. No differences in hunger. To replace fat with fruits and vegetables does not seem to make a difference [as opposed to sugar and refined carbohydrates].)

A low glycemic might be defined as < 50

 Potato, white, baked in skin 85
Whole wheat bread (one slice) 77
Bran flakes cereal 74

Popcorn, microwaved 72 Pineapple, diced 66 Oatmeal instant, cooked 66 Raisins 64

Beets, canned 64
Figs, dried 61
Corn, sweet, boiled 60
Granulated table sugar (sucrose) 68 Brown sugar 59

Kiwi fruit 58 Apricots 57 Banana 52

I tried to eat healthy, by eating: Apples 38
Avocados 0
Cherries, sweet with pits 22 Grapes, green 46

Pears 38

(I ate fruit every day. I had a salad every day with Newman’s balsalmic vinaigrette. I gained 58 lbs. over four years despite two hours of exercise

CAC is the most robust test today to reclassify individuals risk for heart disease. Dr. Budoff

Screening for Heart Disease

By Matthew J. Budoff, MD, FACC

Matthew J. Budoff, MD, FACC

Professor of Medicine

David Geffen School of Medicine

Director of Cardiac CT

Harbor-UCLA Medical Center

Torrance, CA

Cardiovascular disease remains the leading cause of mortality in the U.S. and worldwide, and no widespread screening for this number one killer has been implemented.

Traditional risk factor assessment does not fully account for the coronary risk and underestimates the prediction of risk even in patients with established risk factors for atherosclerosis.

Coronary artery calcium (CAC) represents calcified atherosclerosis in the coronary arteries, and has been shown to be the strongest predictor of adverse future cardiovascular events. CAC consistently outperforms traditional risk factors, inflammatory biomarkers, and other tests of atherosclerosis such as carotid intimal media thickness (CIMT), endothelial function, and ankle-brachial index to predict future CV events.

It (CAC) has been incorporated into both the European and American guidelines for risk assessment.

CAC is the most robust test today to reclassify individuals based on traditional risk factor assessment and provides the opportunity to better strategize the treatments for these subjects (converting 77% of patients from intermediate risk to either high or low risk).

The risk for future adverse cardiovascular events increases with increasing CAC scores; however, the absence of CAC presents a very unique situation that is associated with very low risk status for the individual (10-year event rate of ~1%). It has been proposed that those without calcification may be at such a low risk status that further intervention with pharmacology may be unnecessary. The absence of CAC is associated with a very low risk of future cardiovascular events, presence of severe CAD, myocardial perfusion abnormalities, as well as likelihood of ACS.

The cumulative data provides strong confirmatory evidence that CAC is a strong predictor of events and that as radiation doses are being reduced to a minimum, may be a useful tool in the prevention of armamentarium to assess atherosclerosis progression non-invasively.

Based on available published evidence, CAC has been incorporated into the ACC/AHA guidelines for screening of asymptomatic individuals for CVD.

In this guideline, the cutpoint for CAC is >300, but this is too high a threshold for a score.

The MESA study demonstrated

1- a tenfold increased risk for calcium scores >100 and

2- a 14-fold increase for scores >300.

Both are at increased CV risk and both should be treated aggressively.

All other prospective studies (St Francis, Heinz-Nixdorff Recall Study, Dallas Heart, Rotterdam, and others)

demonstrate that 100 is an important cutpoint for increased CV risk.