{"id":467,"date":"2016-03-15T02:12:50","date_gmt":"2016-03-15T02:12:50","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=467"},"modified":"2016-03-21T00:41:30","modified_gmt":"2016-03-21T00:41:30","slug":"when-your-doctor-suggests-statins-part-1-mechanism-of-action","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2016\/03\/15\/when-your-doctor-suggests-statins-part-1-mechanism-of-action\/","title":{"rendered":"When your doctor suggests statins (Part 1: Mechanism of Action)"},"content":{"rendered":"

High blood pressure is statistically associated with cardiovascular risk. Avoiding salt lowers blood pressure, but it <\/i>does not <\/i><\/b>affect cardiovascular risk.<\/i><\/p>\n

Inflammation is statistically associated with cardiovascular risk. NSAIDs lower the body\u2019s inflammation, and also lowers cardiovascular risk.<\/i><\/p>\n

Statin drugs reduce LDL cholesterol levels in the blood and also quell inflammation. Statins seem to reduce cardiovascular risk. \u00a0Does this have to do with cholesterol or with inflammation?<\/i><\/p>\n

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For almost everyone, LDL cholesterol levels rise during middle age. \u00a0Most doctors will prescribe statin drugs as your first line of defense to lower risk of heart attack. The link between LDL cholesterol and heart disease is not well-established. \u00a0And in any case, there are many things you can do to lower heart risk that are both more effective and have less side-effects than statins. \u00a0I have become convinced that statins are over-prescribed.<\/p>\n

(Too many doctors are still telling patients to cut back on salt. \u00a0They are out of touch with an emerging consensus<\/a>.)<\/p>\n

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 <\/p>\n

Two years ago, I spent a few weeks reading the literature on cholesterol and heart disease, and I reported finding a deep split in the community [Part 1<\/a>, Part 2<\/a>]: \u00a0There are two camps in the research field, one saying that lowering cholesterol levels is the most effective way to control heart risk, and the other saying that cholesterol levels are completely unrelated to heart risk. \u00a0At the time, I didn\u2019t take sides; but now I\u2019m inclined toward the latter group, based on politics as much as science.<\/p>\n

It is difficult to get a man to understand something, when his salary depends upon his not understanding it.<\/i><\/b>
\n<\/i><\/b> \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0— Upton Sinclair<\/b><\/p><\/blockquote>\n

John Abramson, a professor at Harvard Med and author of Overdosed America<\/a>, lists statins as America\u2019s #1 most overprescribed drug class. \u00a0Even for the class of patients most at risk, he estimates that of every 140 people are taking statins, only 1 of them avoids a heart attack. He tells a story of an entire sub-field of medicine that has been touched by money from the pharmaceutical industry. \u00a0Most scientists are smart, honest, and independent. \u00a0But I have found in several areas that scientists are not immune from herd mentality. \u00a0We tend to be trusting creatures, specialized in a narrow field, with faith to accept others\u2019 findings in areas where we are less expert. \u00a0Hence, it is not as difficult as you might think for money to influence a scientific paradigm. \u00a0This is especially so in epidemiology, where large studies of diverse humans are amenable to various interpretations. \u00a0The specialists in physiology are not good at statistics, and the statisticians are not senior authors, but are hired to put numbers together in support of a thesis \u00a0The predominance of private money from drug companies over public money from NIH makes pharmacological science especially vulnerable.<\/p>\n

Abramson\u2019s advice is that statins are appropriate therapy only for men who have already suffered one heart attack. \u00a0For your reference, I\u2019ve posted the key pages from Chapter 9 of his book here<\/a>. \u00a0What he reports is enough to foment a rebellion against for-profit health care, and especially the corporate role in health research. \u00a0After reading it, I was moved to write a column dismissing statin drugs as a well-funded scientific fraud. \u00a0I did not find evidence to support that.<\/p>\n

What I did find, is that the prevailing theory about LDL cholesterol and CV disease has very little support. \u00a0I believe that statin drugs work to lower CV mortality, but that the mechanism for the benefit has more to do with inflammation than with cholesterol. \u00a0This leads to the question: \u00a0Are there better ways to lower inflammation that do not impose the substantial side-effects of statin drugs?<\/i><\/b><\/p>\n

 <\/p>\n

What is a heart attack?<\/b><\/p>\n

Heart attacks result when an artery feeding the heart muscles becomes obstructed. \u00a0Most commonly, deposits (\u201cplaques\u201d) build up on the insides of artery walls over many years, and sometimes pieces of placque break off and become seeds for blood clots that can block the artery enough to cause an attack.<\/p>\n

    \n
  1. The placques are predominantly cholesterol.<\/li>\n
  2. The breakage of the plaques is an inflammation process.<\/li>\n
  3. Clotting of blood is frequently the step that pushes the attack over the edge.<\/li>\n<\/ol>\n

    Viable therapies interrupt the process at any of these three stages.<\/p>\n

      \n
    1. LDL the form of cholesterol in the blood that is most likely to form plaquest, while HDL can actually dissolve the plaques and re-metabolize choleserol. \u00a0Statin drugs lower LDL. \u00a0Exercise, weight loss, a Mediterranean diet, and niacin (vit B3) can raise HDL<\/a>.<\/li>\n
    2. Anti-inflammatories can help keep the artery walls intact. \u00a0Lowering inflammation also lowers risk of cancer, stroke and AD. \u00a0Common anti-inflammatory agents include NSAIDs, fish oil, curcumin, boswellia, and cat\u2019s claw. \u00a0Statin drugs are powerful anti-inflammatories, and there is a school of thought that says that their anti-inflammatory action is more important than their cholesterol-lowering action for preventing heart attacks.<\/li>\n
    3. Anti-coagulants, including NSAIDs and fish oil, protect against heart attacks as well. \u00a0Side effects include risk of internal bleeding, stomach ulcers, and hemorrhagic stroke. \u00a0(13% of strokes are hemorrhagic and come from blood flooding the brain; the rest are ischemic, which means that they are caused by a clogged artery, via mechanisms closely analogous to heart attacks.)<\/li>\n<\/ol>\n

      Congestive heart failure<\/a> is a condition that sometimes precedes or predicts a heart attack, and is a health problem in its own right. \u00a0The cause is often partial blockage of arteries feeding the heart, causing the heart to become weak. \u00a0Common symptoms include decreased stamina, shortness of breath, fluid retention and swelling in the limbs.<\/p>\n

       <\/p>\n

      Statin Drugs Interfere with the Manufacture of Cholesterol<\/b><\/p>\n

      Starting sixty years ago, medical thinking was that it was most powerful and sensible to interrupt this cycle at Stage 1 by lowering the cholesterol in the bloodstream. \u00a0Statins go a step further by actually interfering with the body\u2019s manufacture of cholesterol.<\/p>\n

      \"\"<\/p>\n

      The trouble with this reasoning is that cholesterol is not some unwanted byproduct of the metabolism like lipofuscin or glycated proteins. \u00a0It is not, like adipose tissue, the origin of pro-aging signals in the body. \u00a0Rather, cholesterol is an essential ingredient in the cell metabolism, which the body manufactures abundantly and uses in diverse waves. \u00a0Cholesterol lives in cell membranes, and cholesterol is concentrated in nerve cells, where it plays an essential role as insulator. \u00a0Cholesterol is a chemicl precursor to vitamin D and sex and steroid hormones. \u00a0\u00a0Our brains have more cholesterol<\/a> than any other part of us. \u00a0Cholesterol is the substrate for producing the bile acids that we need for digestion. \u00a0Here<\/a> is a tutorial on the biochemistry of cholesterol in the body, its manufacture, uses and dangers.<\/p>\n

      It should be obvious that shutting off the body\u2019s cholesterol factory is likely to cause many unwanted side-effects. \u00a0A smarter, more focused attack on the particular chemistry of deposits in the arteries is needed.<\/p>\n

       <\/p>\n

      Choesterol and CV disease<\/b><\/p>\n

      Here are results from a classic epidemiological study, based on the Framingham Heart database [1993<\/a>] :<\/p>\n

      The relationship between total cholesterol level and all-cause mortality was positive (ie, higher cholesterol level associated with higher mortality) at age 40 years, negative at age 80 years, and negligible at ages 50 to 70 years.<\/p>\n

      [<\/b><\/em>Note: there are a lot more people dying at age 80 than at age 40. \u00a0The negative relationship at late ages is both more important and better established – JJM]<\/em><\/b><\/p>\n

      The relationship with CHD mortality was significantly positive at ages 40, 50, and 60 years but attenuated with age until the relationship was positive, but not significant, at age 70 years and negative, but not significant, at age 80 years. \u00a0Results for the relationship between low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and mortality help explain these findings. Non-CHD mortality was significantly negatively related to cholesterol level for ages 50 years and above.<\/p>\n

      [<\/b><\/em>Translation: People under 70 who had higher levels of cholesterol had a greater chance of dying of heart disease, but this was compensated by a smaller chance of dying of other causes. – JJM<\/b>] <\/b><\/em><\/p><\/blockquote>\n

      In this study<\/a>, funded by the life insurance industry which ought to have a neutral interest in prediction, only small relationships were found between cholesterol and mortality risk,* and risk was elevated both for low cholesterol and for high cholesterol. \u00a0LDL levels had no consistent relationship to mortality. \u00a0Average levels of HDL were better than either high or low. \u00a0High levels of total cholesterol (TC) presented no additional risk, but very low levels corresponded to a 50-75% increase in mortality. \u00a0These findings may be of limited utility because they are uncorrected for smoking or diet or statins, and are only very crudely stratified by age. The \u201csweet spot\u201d for total cholesterol was about 180-230 for men, 170-220 for women.<\/p>\n

      These two graphs represent all-cause mortality risk for women and men over 60, graphed against their cholesterol level. \u00a01.5 million life insurance applicants (yes – a huge subject pool) have been grouped by percentile. \u00a0The middle half is all lumped together, and the ends of the curve are finely divided. \u00a0What I get from this picture is consistent with noise from the 5th through the 95th percentiles. \u00a0There is no apparent relationship between mortality risk and either total cholesterol or HDL. \u00a0The exception seems to be at the extremes–the highest 1% and the lowest 1% both seem to be at higher risk. \u00a0The highest 1% corresponds to about 334 mg\/dl (F) and 308 (M). \u00a0The lowest 1% corresponds to 146 (F) and 138 (M). \u00a0(There is no corresponding graph for LDL in the article, but the authors report, \u201cUsing LDL or non-HDL cholesterol instead of total cholesterol does not improve mortality risk discrimination; neither does using total cholesterol or triglyceride values in addition to the total cholesterol\/HDL ratio\u201d<\/p>\n

      \"Mortality_vs_Cholesterol_Fgt60\" \"Mortality_vs_Cholesterol_Mgt60\"<\/p>\n

       <\/p>\n

      Anti-Inflammatory action of Statins<\/b><\/p>\n