OBJECTIVE: Statins reduce cardiovascular risk and slow progression of coronary artery calcium (CAC). We investigated whether CAC progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact.
METHODS AND RESULTS: We measured the change in CAC in 495 asymptomatic subjects submitted to sequential electron-beam tomography (EBT) scanning. Statins were started after the initial EBT scan. Myocardial infarction (MI) was recorded in 41 subjects during a follow-up of 3.2+/-0.7 years. Mean LDL level did not differ between groups (118+/-25 mg/dL versus 122+/-30 mg/dL, MI versus no MI). On average, MI subjects demonstrated a CAC change of 42%+/-23% yearly; event-free subjects showed a 17%+/-25% yearly change (P=0.0001). Relative risk of having an MI in the presence of CAC progression was 17.2-fold (95% CI: 4.1 to 71.2) higher than without CAC progression (P < 0.0001). In a Cox proportional hazard model, the follow-up score (p=0.034) as well as a score change > 15% per year (P < 0.001) were independent predictors of time to MI.
CONCLUSIONS: Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events. PMID: 15059806
Cardio Controversies: Dr. Callister MD
I think Callister is cool. First he found statins were associated with regressed EBCT scores in 1998 but then confessed up when he could not replicate it in several subsequent trials. He has even postulated why. Correctly I think!
He and his colleagues have found a dilemma in current cardiology concepts, much like Dr. Superko. Despite LDL < 120 mg/dl and treatment with statins, patients progressed to an MI when the calcium volume score via EBCT increased > 15% annualized. In fact, they summarize that "the relative risk of suffering a MI in the presence of CVS progression was 17.2-fold (95% CI4.1 to 71.2) higher than that of subjects without progression (P < 0.0001)."
Our goal at TYP as designated by Dr. Davis from his extensive experience and research is for EBCT annualized progression of no more than 10% to halt all risk of long-term clinical CAD events. Naturally, some EBCT regression is desirable.
Is LDL Reduction Necessary?
For reduction in hard clinical events, is LDL reduction really necessary? Actually, I don't think so... From lipid researchers like Dr. Barry Sears PhD on omega-3 and the tremendous outcomes from the secondary prevention Lyon Heart Diet trial, we know that with a significant reduction of dietary omega-6 toxic vegetable oils and sufficient increments of dietary omega-3 (ALA, EPA, DHA), clinical CAD events can be nearly halted in very high risk group of CAD individuals. Moreover, with only minor improvements in the n-6:3 balance a reduction in all-cause mortality (cancer, suicides, accidents, etc) in addition to CAD mortality and events was observed in this landmark study. Recall, these improvements were witnessed with no improvements in total HDL (final 49 mg/dl) or LDL (final 161 mg/dl). I always have to ask why save the heart and coronary vessels yet advance to experience cancer and/or suicide and depression? One of the most tragic and saddest stories that I have come across related to the low-saturated fat debacle is that of the famous Dr. Pritikin who conquered heart disease but committed suicide after silently battling leukemia. What was he missing? Could his demise have been prevented?
Low Dietary Saturated Fat
Why may low saturated fat be dangerous for the long-term? Can a 'deficiency' in dietary saturated fat be as insiduous and quietly dangerous as cancer or subclinical atherosclerosis itself?
I see a lot of HDLs in the 20s 30s 40s (or HDL2b nonexistent to single-digit). What is wrong with these kind of numbers? For one, according to clinical trials, they are highly associated with CAC progression and early events. Of course, there are cases that are exceptions to the rule... for instance if you are . . . (1) Nissen infusing HDL-recombinant pieces into your arm every night (JUST KIDDING... don't get any stupid ideas) (2) an apo A1-Milano carrier (3) allergic to kryptonite *haa* (4) consuming boatloads of niacin or omega-3 fish oil until gills grow
Are low HDLs a sign of dietary saturated fat deficiency? Or just high carbohydate intake? Or both? Moreno JA et al showed that with a high fat diet (40%) both high saturated fat (20% SFA) and high monounsaturated fat (22% MUFA), shifted individuals equally from pattern B to A when compared to a high carbohydrate (CHO 57%) diet (J Nutr. 2004 Oct;134(10):2517-22). PDF click HERE. However, these diets in healthy volunteers were still very high carbohydrate at (yikes) 47% and explains why a higher majority of individuals were pattern B (predominance of small dense atherogenic LDL) to begin with, particularly in the males. Certainly, I know I would immediately be clinically T2DM with this kind of diet. Like other saturated fat studies, only the SFA diets across every apo E type (4/3, 3/3, 3/2) raised the HDL to the highest degree. Interestingly, apo-AI was increased as well to the highest degree in the SFA groups across apo E genotypes compared to all other diets. Both HDL and apo-AI are atheroprotective and tremendously related to plaque regression. See below chart (p < 0.05).
Callister's Other Findings: 'Incomplete Effectiveness of Statins'
Callister et al concluded that 'statin resistance' may be responsible for the lack of efficacy for these drugs in preventing hard clinical events observed in this trial. How about...
Lack of HDLs?
Excessive carbohydrates? 47+% Carbohydrates in the AHA 'low fat' diet?
Lack of dietary saturated fatty acids?
The authors concluded that "molecular mechanisms—as yet not fully understood—could help explain the incomplete effectiveness of statins therapy. The HMG-CoA reductase enzyme is a pivotal rate-limiting enzyme in the production of intracellular cholesterol and is selectively inhibited by statins. To inhibit excess synthesis of cholesterol, the HMG-CoA reductase enzyme is degraded in the presence of high levels of intracellular mevalonate and sterols. Statin resistance at the cellular level has been described to occur via 2 mechanisms: overexpression of the gene regulating secretion of the HMGCoA reductase enzyme and loss of degrading ability of the enzyme in cell cultures exposed to high concentration of lipoproteins and lovastatin in the medium."
OK... well they were close. HMGCoA reductase is certainly controlled by several factors. Ness and Chamber discuss this 'cholesterol buffering capacity' effect of HMGCoA reductase, the enzyme that produces LDL-Cholesterol (the good lbLDL and the 'bad' sdLDL) and is mechanistically inhibited by statins. Unfortunately like all interconnected systems in biological environments, feedback control inhibit or stimulate HMGCoA reductase activity ultimately based on many factors which are regulated by needs for growth, reproduction, fasting v. fat-storage and relaxing. Click HERE. --dietary cholesterol downregulates (yup... cheap-egg-yolks vs. Crestor; yolks WIN) --hyperinsulinemia turns it on (poor glycemic diabetic control, high-carbs-low-fat-idiocy, again) --hypothyroidism turns on --peri- and menopause (low estrogen states -- or like those induced by $*%&@# contraceptives and $*%&^! progestins) --high cortisol (mental stress, physical stress) --lack of bile salts (taurine deficiency)
Factors NOT Affected by Statins: Lp(a), IDL, Small LDL, Microbes
Callister and the other authors are brilliant! In addition, they concluded: "Because we did not measure hemoglobin-A1c, we were unable to verify whether the glycemic control had an effect on CVS progression and development of MI. Lipoproteins not affected—or incompletely affected by therapy with statins—such as Lp(a), small dense LDL, and other mediators of vascular damage (viruses, homocysteine, fibrinogen, Chlamydia Pneumoniae, and others) may also have played an important role that could not have been detected because of the design of our study."
What Does Lower Lp(a), IDL, Small Dense LDL and Microbial Burden?
Oh please... Gentle Readers... I hope you get this correct.
Saturated fatty acids, my dear audience members, of course.
Synergistically with a low LOW carbohydrate diet (or no carb).
Did you know that coconut oil, grassfed ghee/butter, cream, tallow, lard (which contain short-, medium- and long-chained saturated fatty acids) control and kill yeast, parasites and other microbes like Salmonella and Campylobacter, in vivo and in vitro?
Krauss is in the House! The Three Axes of Evil
Yes -- of course (without Superko's help) Krauss has figured it out again and confirm the theories above as well as what we already acknowledge and tackle at TrackYourPlaque. Subfraction of lipoproteins yields the 'death' bands on ion mobility analysis which are independent subsets of cardiovascular risk. (Krauss et al, Arterioscler Thromb Vasc Biol. 2009 Sep 3. Not free yet.)
(PC2) Metabolic Syndrome/Hyperinsulinemia pattern of decreased large HDL, increased small/intermediate LDL, and increased triglycerides (eg, Pattern B)
(PC3) HDL-associated protection: large HDL2b subfraction ('absent' band)
Note: Krauss does not list Large LDL-P as one of the axes of coronary risk. After reviewing 3 large landmark trials, he and the other researchers concluded Large LDL are not associated independently with CAD risk. Again, the presence of small LDL-IVb (the smallest of 7 subparticles) is associated with risk and progression of plaque, not a high particle count of Large LDL.
Krauss and the other authors state, "Our study demonstrated that... (1) levels of small/medium LDL particles are associated with [CV disease] and (2) levels of large LDL particles are not significantly related to cardiovascular disease, is consistent with other large prospective cohort studies whose data were obtained by 2 diffeent lipoprotein measurement techniques: the Quebec Cardiovascular Study (GGE) and the Multi-Ethnic Study of Atherosclerosis and Women's Health Study (NMR). (p. 5)"
Paleo folks sometimes have very high LDL counts, like longevity and centenarian studies. If these are all large, no problem. If there are some small dense stuff (LDL-IVb), then it maybe a problem.
Only subfraction of the lipoproteins will identify the culprit.
Do statins help with any other of the above PC1, PC2, or PC3? Well...they may raise HDL max 5-15% whereas niacin raises HDL 30-200% (depending on duration and patient population). Niacin also lowers Lp(a), small dense LDL/IDL, triglycerides and provokes shifts to Pattern A. In the HATS trial, recall, after 3 yrs, niacin raised HDL 30% and HDL2 60%. Niacin was associated also with reductions in blood pressure too. Statins are not in any trial.
In fact, any therapeutic intervention (non-synthetic) that raises HDLs also lowers Lp(a), IDL, small dense LDL/medium LDL and triglycerides. Indeed, they improve in parallel. Conversely, they are exacerbated in parallel. Any strategy that raises HDLs also lowers blood pressures (eg, body fat loss, lean muscle gain, yoga, omega-3, vitamin D, thyroid replenishment, hormone optimization, many antioxidants).
Except statins. What the authors missed mentioning was that additionally statins worsen Lp(a) and percent-sdLDL. And they fail to shift to pattern A. What else? Statins s*ck.
Correctly Catching the Calcification Culprit(s)
TrackYourPlaque is a self-management program. To optimize the program and control plaque, one must accurately and knowledgeably assess personal and familial risk factors that caused subtoptimal lipoproteins and/or positive EBCT scores and progression. The three factors listed above comprise 99% of the most common coronary culprits.
If one is just trying to beat down the LDL-Particle Count into submission and fails to take into account the three 'axes' of coronary risk, one will invariably miss the big picture.
Is it... dangerous...??
Certainly... it is not equivalent to EBCT stabilization or regression. Targeting and ameliorating the correct coronary culprits on the other hand yields potent control on plaque and reduce EBCT calcification progression to < 10%. For regression in 8-16 months on EBCT, perfect lipoproteins definitely are not mandatory but a trend toward improvements in both reductions in small LDL, IDL, Lp(a) and increases in HDL2 and relative LDL-buoyancy are requirements. Control of hypertension, more vitality, loss of body fat are all extra side perks.
Do you have 'leaky gut' where microbes are flowing into the blood stream from the intestines? Do you have low HDL? Do you have high small-LDL? Do you have Pattern B? Do you have Lp(a) and/or high homocysteine? Do you have a progression or calcium score > 10% annualized? Do you have premature CAD or stroke or peripheral vascular disease or renoarteriosclerosis in your family history? Do you have proteinuria, dialysis or chronic kidney disease in your family? Do you have heart failure in your family history? Do you have 'statin resistance'?
Then... one cannot hesitate or prolong an approach that is more targeted and aggressive than the one that Callister and his colleagues discussed ('incomplete effectiveness') associated with a 17.2-fold MI-risk in 6-7 years.
Ketosis/niacin, low LOW carb Paleo diets, mod-high SFA diets, high omega-3 supplementation, dietary omega-6 elimination, hormone optimization, cardio/weights and many MANY other TrackYourPlaque strategies improve allthree axes of high cardiovascular risk.
I had my APOe and lipids classified by Berkley Labs. It was pretty affordable (out of pocket was about $150). Very cool stuff, how they can classify your diet, fine tune your medications, and risk propensity based on genotype markings is pretty incredible. They also recommended a
glycemic index diet plan.