Tuesday, April 08, 2008

Cholesterol, MESA and EBCT

Thanks to Dave Lull for a copy of the latest MESA paper. I guess you could just say EBCT looks like a good predictor of heart attack risk, irrespective of age or ethnicity and leave it at that. It looks to be true.

I was just browsing through table one of the results and a few strange things came out. First is that it doesn't include LDL cholesterol at baseline! Most people with any shred of intelligence will realise that calculated LDL cholesterol is garbage, but it's not typical of the average cardiologist to get that far.... These guys must be good!

The second gem was that HDL was lower in the coronary event group, as happens in Framingham. But the difference between the means was 51.0 minus 47.3, I make that 3.7mg/dl. The standard deviation was 15 ish in both groups. If they had a Normal Distribution, which they should have, the range to include most participants is about three standard deviations around the mean. The overlap is phenomenal between heart attack and non heart attack groups. On a personal basis having an HDL of 20 could easily put you in either group, as could an HDL of 60. I guess cardiologists just get used to this.

Taking lipid lowering medication appears to be as bad as being a current of former smoker. Must be a message there but I can't work it out...

Anyone tempted to crash diet might be disappointed by the BMI in the coronary event group being .2 units lower than the spared group. Good job this has neither biological or statistical significance, or participants might have to be encouraged to gain a few pounds. Or get shorter!

I know all of these things need to be factored in to correct for know interactions as it's likely that all of the diabetics were on statins while being encouraged to eat healthy starches and shoot up with insulin, but the raw data still give me a chuckle.

So Detrano et al provide more evidence that coronary calcium, the physical evidence of on going disease, is a better marker of a physical on going disease process than a surrogate of any sort. They also seem less wedded to conventional risk factors. But I guess that's why they're doing the study...

Peter

10 comments:

Stephan said...

OK, so here's the new hypothesis. Low HDL and high trigs are simply markers of high carb intake, nothing more. In grain-based nations, the carb is mostly from grains, so they're markers for grain intake. If we believe that grains are bad, it all makes perfect sense. That would explain why HDL:trig ratio seems to be so important in grain-based cultures but meaningless in Kitava.

Chainey said...

This post settles it: I'm changing from a high HDL diet to a low calcium one. How can I get all that nasty calcium out of my body so it won't show on the pictures?

Also, if it's bad to be a former smoker (as I am) or a current one, at what time in the future should I take it up again?

Charles R. said...

Peter: take a look at this:

http://tinyurl.com/65hrkl

Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance

Previous studies have suggested that insulin resistance develops secondary to diminished fat oxidation and resultant accumulation of cytosolic lipid molecules that impair insulin signaling. Contrary to this model, the present study used targeted metabolomics to find that obesity-related insulin resistance in skeletal muscle is characterized by excessive β-oxidation, impaired switching to carbohydrate substrate during the fasted-to-fed transition, and coincident depletion of organic acid intermediates of the tricarboxylic acid cycle. In cultured myotubes, lipid-induced insulin resistance was prevented by manipulations that restrict fatty acid uptake into mitochondria. These results were recapitulated in mice lacking malonyl-CoA decarboxylase (MCD), an enzyme that promotes mitochondrial β-oxidation by relieving malonyl-CoA-mediated inhibition of carnitine palmitoyltransferase 1. Thus, mcd−/− mice exhibit reduced rates of fat catabolism and resist diet-induced glucose intolerance despite high intramuscular levels of long-chain acyl-CoAs. These findings reveal a strong connection between skeletal muscle insulin resistance and lipid-induced mitochondrial stress.

Peter said...

Hi Charles,

Interesting study, worth a post on its own. You need the full text to appreciate it. I'm in luck for this one with my Athens account!

Peter

Paul said...

Peter,

A misuse of comments on the current topic, but I guess there is no mechanism to contact you directly - Eades' latest post on vegetarianism and AGEs will undoubtedly be of interest if it's not already on your radar

http://tinyurl.com/6n4p7v

Paul.

Peter said...

Hi Paul,

Got it, thanks

Peter

Frank said...

Isolated myotubes don't count; in vivo the myocytes are protected from ceramide toxicity by the presence of leptin. The fitness of the metabolic switch (between FAs and glucose) is the key factor in glucose intolerance and metabolic syndrome.
Love the blog BTW thanks.

Willow said...

People who develop Cushing's Syndrome as a result of taking prescribed steroids, HRT or tricyclic antidepressants, etc have massive sodium and water retention (the cause of the Cushing's Syndrome). They also frequently develop Hypercholesterolaemia among a host of other associated healthconditions. It is my belief, therefore, that sodium retention is a significant causative factor for Hypercholesterolaemia. Since the Cushing's symptoms lessen when salt/sodium intake is lessened, I reckon Hypercholesterolaemia will be lessened if you cut down on salt/sodium.

See http://www.wildeaboutsteroids.co.uk/conditions.html and http://www.wildeaboutsteroids.co.uk/sodium_foods.html

Peter said...

Willow,

The hallmark of Cusjings is elevated cortisol. I can't see salt as a cause, more convincing is sodium retention is a side effect, I don't see the physiology for causation. Giving mitotane, trilostane or ketaconazole normalises cortisol, steroid induced hypercholeterolaemia (in species which get this aspect) and eliminates sodium retention w/o salt restriction.

Peter

Willow said...

Peter,

Sodium retention and water retention are different terms for the same thing. The steroids like prednisone, prednisolone and HRT (the oestrogen component) relax the muscles in the walls of the blood vessels, so that they become vulnerable to the incursion of any excess sodium and the water it attracts to itself. - Steroid victims then develop hugely dilated veins and of course experience weight gain and higher blood pressure. From this fluid retention, fat retention can also follow because fluid retention depletes the body of calcium, and insufficient calcium results in fat retention.