{"id":58192,"date":"2009-11-06T18:19:12","date_gmt":"2009-11-06T23:19:12","guid":{"rendered":"http:\/\/www.proteinpower.com\/drmike\/?p=3760"},"modified":"2009-11-06T18:19:12","modified_gmt":"2009-11-06T23:19:12","slug":"statinators-spill-the-beans","status":"publish","type":"post","link":"https:\/\/mereja.media\/index\/58192","title":{"rendered":"Statinators spill the beans"},"content":{"rendered":"

Oftentimes people become so fixed in their thinking – and in their belief that everyone else thinks the same way – that they unwittingly raise the curtain and expose the wizard of their flawed thinking, showing it for what it really is.\u00a0 Statinators have done just that in an article in the current issue of the Journal of the American College of Cardiology (JACC)<\/em>.<\/p>\n

The study, Effects of High-Dose Modified-Release Nicotinic Acid on Atherosclerosis and Vascular Function<\/a>, compares the increase in carotid artery plaque over a 12-month period in subjects taking niacin versus those taking a placebo.\u00a0 It turns out that those subjects taking the niacin experienced a shrinkage of their plaque whereas plaque grew larger on those taking the placebo. The revealing hitch in this study is that both groups were on statins, which means the group on statins alone was the placebo group.\u00a0 Therefore the data from this study shows that statins alone do not reverse the growth of plaque (at least not plaque in the carotid arteries) despite lowering LDL levels.\u00a0 Taking the logic a little further, the data from this study gives weight to the idea that a lowered LDL doesn\u0092t reduce plaque growth.<\/p>\n

There is a lot we can glean from this study and the from the authors\u0092 commentary on it.<\/p>\n

Let\u0092s take a look.<\/p>\n

Researchers randomized 71 subjects–all of whom were on statins and all of whom had low HDL-C and either a) type II diabetes with coronary artery disease or b) carotid or peripheral atherosclerosis–into two groups.\u00a0 The researchers did magnetic resonance imaging (MRI) studies of the carotid arteries of both groups, then started the subjects in the study group on niacin while the subjects in the other group got a placebo.\u00a0 Subjects in both groups continued with their statin therapy.\u00a0 At six months and one year later, MRI studies determined the degree of carotid atherosclerosis and whether it had increased, decreased or remained the same.<\/p>\n

After one year, it was found that the subjects receiving the niacin along with their statin significantly reduced their carotid atherosclerosis as compared to those subjects on placebo.\u00a0 And remember, the placebo group of subjects were also on statins and still experienced an increase in their carotid atherosclerosis.<\/p>\n

Almost 90 percent (63) of the 71 subjects were males with an average age of 65.\u00a0 As I\u0092ve discussed previously<\/a>, there is no evidence that statins provide any benefit in terms of decreased overall mortality to females of any age or to men over the age of 65 regardless of their state of health.\u00a0 The only group that statins has shown to provide any benefit for in terms of decreases all-cause mortality (the only statistic that really counts) is men under the age of 65 who have been diagnosed with heart disease.\u00a0 Even in that group, benefit is so small<\/a> as to be questionable.\u00a0 Knowing this, we can say (assuming an equal distribution of under 65 and over 65 to get an average of 65 years old for the group as a whole) that the majority of people in this study were taking statins unnecessarily.\u00a0 Those males in the study who were under 65 and who had been diagnosed with heart disease were really the only ones who (according to all published research) may<\/em> have received long-term benefit from the statin therapy.\u00a0 This aside has nothing to do with study or its outcome, it\u0092s simply my commentary on the widespread overuse of statins. So back to the study…<\/p>\n

The authors reported on changes in blood values, blood pressure and body weight between the groups:<\/p>\n

\n

In the NA-treated [niacin-treated] group, mean HDL-C increased by 23% and LDL-C was reduced by 19% at 12 months. Triglycerides, apolipoprotein B, and lipoprotein(a) were significantly decreased by NA compared with placebo. CRP was decreased by NA compared with placebo (p = 0.03 at 6 months, p = 0.1 at 12 months). Adiponectin was significantly increased at both 6 and at 12 months (p < 0.01). From the safety perspective, minor transient elevations were noted in creatine kinase and liver enzymes, but no significant, sustained elevations (>3\u00d7 the upper limit of normal for 2 weeks) were observed in any subjects. Fasting glucose did not change significantly, but glycated hemoglobin showed a small increase in the NA group versus placebo (p = 0.02 at 6 months, p = 0.07 at 12 months). Blood pressure and body mass index did not change significantly in either group.<\/p>\n<\/blockquote>\n

As any of you who have taken niacin will understand, about 10 percent of the subjects dropped out because they couldn\u0092t tolerate the flushing, itching and GI side effects of the niacin. (Some people have had good luck with taking niacin as inositol hexanicotinate, marketed as ‘No-flush Niacin’ though the tolerance for this form isn’t perfect either.)<\/p>\n

Those subjects who were able to tolerate it had niacin (nicotinic acid) added to their statin dose and experienced a slight decrease in carotid plaque volume.\u00a0 Meanwhile those on statins alone had their plaque volume increase.\u00a0 Below is a representative MRI showing the difference:<\/p>\n

\"NA<\/p>\n

To the untrained eye, these kinds of studies are difficult to read.\u00a0 Even to the trained eye, they can be misread, so there have been computer programs designed to calculate the plaque area so that it can be quantified.\u00a0 You can see the results graphically below:<\/p>\n

\"NA2\"<\/p>\n

Before we all start thinking the combination of statins and niacin (nicotinic acid in the graph) is the second coming as far as atherosclerosis treatment is concerned, let\u0092s be aware of a couple of facts.\u00a0 First, these differences in plaque volume don\u0092t really mean squat in terms of blood vessel functionality.\u00a0 As the authors stated:<\/p>\n

\n

Neither aortic distensibility nor flow-mediated dilation of the brachial artery was significantly altered by [niacin] treatment.<\/p>\n<\/blockquote>\n

The terms “aortic distensibility” and “brachial artery dilation” are measures of arterial function, and neither changed.\u00a0 Also, as you can see from the MRI above, the differences in plaque size don\u0092t seriously compromise the open area in the artery through which blood flows.<\/p>\n

The fact that none of these indicators of functionality changed and the plaque shrinkage didn\u0092t make a measurable dent in the blood-carrying capacity of the arteries means that none of these subjects really got any short term benefit from the therapy in terms of true risk reduction.\u00a0 Maybe subjects who were worse would have, but we don\u0092t know.\u00a0 And maybe if the therapy continued for the long term, really remarkable changes between the two groups would begin to become manifest. But we don\u0092t know that for sure, either.<\/p>\n

What I found the most interesting about this study is what it didn\u0092t say.\u00a0 Or, I guess, a better way to put it is what it said, but probably didn\u0092t intend to say.<\/p>\n

If you were to ask any statinator worth his\/her salt what it would take to really significantly reduce the risk for heart disease, he\/she would tell you to try to get LDL-cholesterol levels below 100 mg\/dl.\u00a0 If you then asked, “Well, what about if we got those levels to 80 mg\/dl, what then?”\u00a0 You would be no doubt told that the risk for heart disease would then be minimal.<\/p>\n

Well, the subjects on placebo – those on the statin alone – in this study had their LDL-cholesterol levels below 100 mg\/dl.\u00a0 In fact, at baseline their LDLs averaged 84 mg\/dl and fell to 80 at six months and one year.\u00a0 Yet their plaque continued to grow.<\/p>\n

We can conclude from this study that reducing LDL to these low levels doesn\u0092t stop plaque growth.\u00a0 We might also conclude that LDL levels may not have a whole lot to do with heart disease.\u00a0 We can\u0092t really make that conclusion definitively from this data, but it sure adds strength to that hypothesis.<\/p>\n

In an JACC<\/em> editorial<\/a> (available by subscription only) about this study, the author begins thus:<\/p>\n

\n

Despite the substantial clinical benefit offered by potent low-density lipoprotein (LDL)-reducing therapeutics such as statins, a majority of patients will still experience major cardiovascular events.<\/p>\n<\/blockquote>\n

Hmmm. Let\u0092s tease out all the information loaded into this one sentence.<\/p>\n

Despite \u0093substantial clinical benefit\u0094 provided by statins means the substantial treatment of lab values, i.e., LDL-cholesterol lowering.\u00a0 Statins lower LDL-C; no one denies that.\u00a0 But to what end?\u00a0 The last half of the sentence tells us:\u00a0 A \u0093majority of patients will still experience major cardiovascular events.\u0094\u00a0 If what you\u0092re trying to do is reduce LDL levels, sounds like statins are the drug of choice.\u00a0 But if what you\u0092re trying to do is reduce heart disease, maybe not.<\/p>\n

We know for certain that statins reduce LDL, so the sentence also tells us that LDL may not have squat to do with heart disease, since significantly lowering it obviously doesn\u0092t accomplish a lot.<\/p>\n

Now, here\u0092s how the authors of the paper started out in their introduction:<\/p>\n

\n

Atherosclerosis is a systemic condition in which coronary, carotid, and peripheral arterial disease frequently coexist.\u00a0 In patients with atherosclerotic disease, low-density lipoprotein cholesterol (LDL-C) reduction with [statins] has consistently shown reduction in major cardiovascular events and mortality.\u00a0 However, treatment of LDL-C with statins prevents only a minority of cardiovascular events.<\/p>\n<\/blockquote>\n

Another few sentences filled with interesting truths.\u00a0 What the authors say about statins reducing \u0093major cardiovascular events and mortality\u0094 is true as long as the word \u0091mortality\u0092 is associated with \u0091cardiovascular.\u0091\u00a0 In those who take them, statins do indeed reduce the incidence of cardiovascular events and deaths due to cardiovascular events.\u00a0 What isn\u0092t said in this sentence is that the decrease in cardiovascular deaths the statins prevent is more than made up for by deaths from other disorders that statins likely cause. As far as your risk for death is concerned, taking statins is a zero-sum game: you don\u0092t die from heart disease but you do die from something else within the same period.\u00a0 What you want to do is not to die.\u00a0 Or at least not for a long time.\u00a0 You want to decrease your all-cause mortality, i.e., deaths from all causes, not simply switch from one form of death to another.<\/p>\n

Also in the above paragraph, the authors – statinators to a man (or woman), I\u0092m sure – state that treatment with statins \u0093prevents only a minority of cardiovascular events.\u0094\u00a0 From this last sentence, we can once again draw the conclusion that – at least in the minds of true believers of the lipid hypothesis – lowering LDL doesn\u0092t do diddly to reduce heart disease.\u00a0 Yet they all continue to try to treat it by lowering LDL.<\/p>\n

I\u0092m glad researchers are looking at niacin as a supplement to be used in the treatment of heart disease.\u00a0 As I\u0092ll discuss below, they have ulterior motives in doing so, which is why they combined niacin with a statin instead of having an arm of the study with niacin alone.\u00a0 About 12 or 13 years ago MD and I found ourselves FAB (flat-a**ed broke) after sending three children through expensive private universities.\u00a0 We had just written and published Protein Power, but it hadn\u0092t started to sell, and we didn\u0092t know if it ever would.\u00a0 Our agent approached MD (who can write like the wind) about being the ghostwriter for one of the major university family medical guides (I can\u0092t tell you which one, but it\u0092s one of the Harvard-, Johns Hopkins-, Mayo Clinic-type of giant family medical guides than many of you may have in your homes) for a nice chunk of change.\u00a0 She didn\u0092t want to do it, and I didn\u0092t want her to do it, but we decided that she should because it would probably make Protein Power a success.\u00a0 Why did we decide this?\u00a0 Because that\u0092s how fate works.\u00a0 We reasoned that if we didn\u0092t take the deal, Protein Power would die on the vine, and we would be wishing that we had taken it.\u00a0 If we took it and Protein Power took off, then we would be wishing that we hadn\u0092t taken the ghost writing deal and could buy our way out.\u00a0 We took it, Protein Power took off (thank God), and MD bought out of her contract after having written about four fifths of the book.<\/p>\n

During this awful project, I did a lot of the research and MD did all the writing.\u00a0 Plus MD did all the teleconferences with the major university honchos whose names are actually on the book.\u00a0 After each of these conferences she would run for the wine, because these guys (all were guys) were so detached from reality that it was impossible to deal with them.\u00a0 They were so hidebound in their mainstream way of thinking that no amount of reasoning could dissuade them.\u00a0 Which is why MD didn\u0092t want her name anywhere on the book.\u00a0 She didn\u0092t want to be associated with such idiocy when she had had years of hands-on clinical practice teaching her that most of what these people – who probably hadn\u0092t treated patients in years, if ever – believed was bunk.<\/p>\n

Where this dreary tale is leading is that during the research for this book, we determined from all the published data out there that niacin was the only substance that had ever been shown to actually reduce all-cause mortality in cardiovascular patients.\u00a0 That was in the mid-to-late 1990s and now they\u0092re just getting around to evaluating it again.<\/p>\n

So why after all these years are they now looking at niacin in conjunction with statins in this study?<\/p>\n

Follow the money.<\/p>\n

Robin Choudhury, in whose lab this study was done, is on the payroll of several statin manufacturers, including Merck.\u00a0 The study was underwritten by Merck, the maker of Mevacor and Zocor.\u00a0 Okay, so why would statinators and statin manufacturers want to add what is basically a nutritional supplement to their beloved statins?\u00a0 A discussion in an online cardiology site tells the tale.<\/p>\n

From heartwire<\/a> (requires free registration):<\/p>\n

\n

The paper comes as anticipation builds for the ARBITER-HALTS\u00a06 study results. ARBITER-HALTS\u00a06 is an imaging study comparing changes in carotid intima-media thickness in patients treated with ezetimibe (Zetia, Merck\/Schering-Plough) or extended-release niacin; market analysts are already predicting a win<\/a> for niacin. As previously reported by heartwire<\/a>, ARBITER-HALTS\u00a06 was stopped early: full results will be presented Monday, November 16, 2009 at the American Heart Association meeting in Orlando, FL.<\/p>\n<\/blockquote>\n

So, it appears that extended-release niacin is going to kick tail when compared heads up to Zetia, or at least that\u0092s the way the market is betting it.\u00a0 And that\u0092s usually because the market has info that the rest of us don\u0092t.\u00a0 If niacin is the clear winner, the press will be all over it and many people (and their physicians) will be wanting to switch from other cholesterol-lowering drugs to niacin.<\/p>\n

With this study in hand, Merck and the other statin manufacturers can say, “Don\u0092t give up your statins; the science shows that statins plus niacin is the effective combo.”\u00a0 Just keep your statin and add some niacin. And prescription niacin, to boot, so it all stays in the Big Pharma family.<\/p>\n

Which is why – as heartwire reported – this paper is coming out now: to beat the rush.<\/p>\n

We’ve learned a couple of things from this study.<\/p>\n

First, we’ve learned that we have here a randomized, double-blind, placebo-controlled study showing that statins reduce LDL but don’t stop the progression of atherosclerosis, which, after all, is why we would take them.<\/p>\n

And we have learned from reading between the lines in this study that statinators don\u0092t really believe their own hype.\u00a0 As Samuel Johnson said about second marriages, the statinator\u0092s reliance on statins as a cure all for heart disease \u0093is a triumph of hope over experience.\u0094\u00a0 Things haven\u0092t really changed since MD wrote the family medical guide. If you\u0092re worried about heart disease, take some niacin, the only substance yet that has been shown to decrease all-cause mortality. And it doesn\u0092t have to be the prescription variety.<\/p>\n


\n\"\"<\/a><\/p>\n

\n<\/img><\/a> <\/img><\/a> <\/img><\/a>\n<\/div>\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Oftentimes people become so fixed in their thinking – and in their belief that everyone else thinks the same way – that they unwittingly raise the curtain and expose the wizard of their flawed thinking, showing it for what it really is.\u00a0 Statinators have done just that in an article in the current issue of […]<\/p>\n","protected":false},"author":108,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-58192","post","type-post","status-publish","format-standard","hentry","category-news"],"_links":{"self":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/posts\/58192","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/comments?post=58192"}],"version-history":[{"count":0,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/posts\/58192\/revisions"}],"wp:attachment":[{"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/media?parent=58192"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/categories?post=58192"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mereja.media\/index\/wp-json\/wp\/v2\/tags?post=58192"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}