Thursday, February 28, 2008

The New Hub-Bub Over Metabolic Syndrome

Metabolic Syndrome has long been identified as a risk factor for heart disease. However, idientifying exactly what it is and what its cause or causes are has been a subject of much debate. Now, a new study published in Cell Metabolism has thrown the issue into a full-fledged brouhaha over whether Metabolic Syndrome is a multi-cause condition or more simply a single cause condition with multiple symptoms. For example, is small-LDL a contributor to a diagnosis of Metabolic Syndrome or is some other single root cause driving a host of symptoms such as small-LDL to appear.

The Multi-Cause camp has labored long and hard at defining what group of causes is sufficient to render a diagnosis of Metabolic Syndrome. Different organizations have different standards but all require having some combination of common symptoms such as:

Here are links to the various guidelines NCEP ATP III (what most U.S. doctors use), American Heart Association, World Health Organization (pages 32 and 33), European Group on Insulin Resistance (EGIR).

This latest study by the Joslin Diabetes Center focuses on insulin resistance in the liver as the key factor in the cause of metabolic syndrome and its association with heart disease. It advances the theory that metabolic syndrome is not simply a collection of abnormalities that should be treated independently but a group of closely linked disturbances in glucose and cholesterol metabolism that stem from a defect in insulin signaling in the liver. This thinking suggests the cure for Metabolic Syndrome is not to treat a variety of symptoms but rather to find and treat the underlying cause perhaps with a single "magic bullet." This is tantatmount to treating and eliminating a cold virus rather than treating the associated symptoms aches, sore thoat, congestions, and sniffles associated with the cold.

OK, great! Now let's find that magic bullet!


Wednesday, February 13, 2008

Do YOU Worship at the Alter of LDL Cholesterol?

Many years ago, doctors would simply measure total cholesterol and call it a day. As the snail-slow medical community progressed it identified LDL Cholesterol as the "bad" guy and basically did little else for decades but beat up on LDL and develop LDL lowering drugs like statins and, more recently, ezetimibe. But a funny thing happened on the way to the temple.

Much like the COURAGE trial delivered a much different than expected result on stenting (it's not much better than drug therapy for non-acute heart disease) , the ENHANCE trial found that lowering LDL with ezetimibe provided little improvement in outcomes. Track Your Plaque proponent Dr. William Davis often opines, "The average LDL Cholesterol of a heart attack victim is 134mg/dl, the average LDL Cholesterol for someone who does not have a heart attack is 131mg/dl." It is a statistical dead heat!

The latest theory is that what matters most is not merely how low you drive LDL Cholesterol but how you go about lowering it (statins deliver pleiotropic effects beyond simply lowering LDL). Ezetimibe can dramatically lower LDL when taken in combination with a statin. You have probably seen the commercials for Vytorin (simvastatin plus ezetimibe) that proclaim it treats the "two sources of cholesterol" (genetic and dietary). The ENHANCE studiers naturally expected to prove ezetimibe was a blockbuster drug that whose LDL lowering effects would earn billions. But it didn't happen. Moreover, the researchers were accused of delaying publication of the bad news.

Dr. Eric Topol has an interesting Video Blog on the subject that is worth the 4-1/2 minutes of your time to see and hear. He suggests that the true cuplrit is oxidized LDL. It makes a lot of sense as we begin to "peel back the onion" on LDL Cholesterol. Stay tuned! You know my next move. Find a test for it so I can hang on number on it!



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