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From: "Steve Harris" <>
Subject: News on C-rective Protein and LDL, with notes by S. Harris
Message-ID: <NXOg9.6807$>
Date: Sat, 14 Sep 2002 22:42:53 GMT

This week's news on C-reactive protein and LDL, with notes by S. Harris.

Ostler once remarked that the doctor who understands syphilis understands
medicine. The closest we can come to such a statement in today's world might
be that the doctor who understands the _inflammatory response_ understands
medicine. Inflammation is responsible for the classical signs of disease in
the ancient Galenic view (rubor, calor, tumor, dolor = redness, heat,
swelling, pain), and very often inflammation is partly responsible for the
fifth sign of disease that historically was added in the middle ages:
dysfunction. Treatments which affect inflammation, such as application of
heat and cold, were (and are) strangely powerful in general medical care. As
are foods and drugs that modulate the process: the story of aspirin is
familiar, but other antiinflammatories have had a long history as "nostrums"
simply because they affect symptoms of so many diseases positively. For
example, the body oil of the Chinese water snake, which is 20% EPA (an n-3
fatty acid also common in fish) was long sold as a cure for rheumatism and
aches and pains anywhere. Thus the pejorative "snake oil."  But the stuff
probably worked like aspirin, because today we know that (in general) the
3-series prostaglandins made from n-3 fatty acids are not as inflammatory as
the more common ordinary kinds. Fish oil is good for arthritis, and so is
snake oil. Take that, quackbusters.

Inflammation is a two-edged sword, and so is the suppression of it. Modern
medical care consumes vast amounts of anti-inflammatories, with such gusto
and with so many negative consequences, that these drugs are probably
responsible for the majority of serious outpatient drug reactions. The
modern doctor spends time thinking about inflammation and its direct and
indirect consequences every day.

Inflammation causes symptoms, but as regards the actual pathogeneisis of
some disease, inflammation is beginning to look like it often has a role
here also.  To be sure, inflammation helps healing, and helps with bacterial
infection, but our inflammatory responses are built to deal with small
bacterial infections and small wounds. Here is where the two edges of the
sword come in: in the case of gross systemic infections (septic shock),
large traumas, ischemic/reperfusion injury, and the like, the inflammatory
response may well be inappropriate, since evolution didn't design us to
survive these anyway. For example: inflammation after brain ischemia is now
known to cause some of the damage of post-resuscitation syndrome, and we
have recently discovered that it can be partly blocked by application of low
temperatures, in just the same way that immediately putting a burned finger
or a twisted ankle in cold water helps to limit the damage for these
tissues. Cooling the brain is the first resuscitation treatment which has
actually worked in a clinical trial, and there is much more to come.

Another example: the inflammatory response to the degeneration of old age
may also in many cases be inappropriate, since the problem there is not an
injury which is capable of being fully healed. Think of degenerative
arthritis and the chicken-and-egg role which aging and chronic inflammation
play. More on this later.

Most recently, both atherosclerosis and Alzheimer's disease have been
prospectively associated with chronically elevated levels of inflammation in
the body (as measured by by the inflammatory mediator C-reactive protein
(CRP) levels) long before the disease pathologies manifested themselves
(scientists checked stored blood from people who developed the diseases
years later). Is CRP merely a confounder (ie, marker variable)--- or is it a
player?  From the independent and powerful association CRP and
atherosclerosis, which we've yet to control for by using any other risk
factor for atherosclerosis, we suspect it's a player. CRP is as good a
predictor of heart disease as LDL cholesterol levels, but independent of
them. Of course, in the absence of prospective interventive trials, we don't
know for sure if CRP is a causal agent in atherosclerosis, but we do have
some mechanistic evidence to tie CRP causally into the general process. We
do know that CRP causes macrophages to take up LDL cholesterol (a key step
in atherogenesis), and in the news today it has been reported that CRP
actually binds to oxidized LDL, and thus may trigger off the immune system
inside vessels by that mechanism (news report appended).

There is of course by now an inflammatory theory of aging (see below-it's
one of dozens of "theories" of aging that are now out there seeking
support). It's known that many markers of systemic inflammation go up in
aging, and also from simply being obese (IL-6 and TNF levels). It's also
known that dietary restriction (DR) in animals (which retards aging) blocks
this rise in these two mediators. So the "inflammatory theory of aging" is
in some ways Dr. Roy Walford's old autoimmune theory of aging, now picked up
and dusted off a little for the modern world. As for the newer mediator CRP,
it isn't known (so far as I can tell) what happens to CRP levels in animals
on DR, but in humans there is epidemiologic and direct experimental data
that the fatter you are, the higher your CRP is, and that losing weight
causes it to drop (see abstract appended). It is quite probable that there's
a direct connection between obesity and CRP, and from there it's possible
that obesity connects to who-knows what problems associated with aging.

An example of where this might occur: we know that obesity is certainly
associated directly and causally with some inflammatory problems which are
age-related. It has recently been shown that Labrador dogs gets less
age-associated osteoporosis, as well as live longer, if they are
calorie-restricted. Also, we know that obesity is an independent risk factor
for not only osteoarthritis of the knees, but also the HANDS in humans.
Unless these obese people are walking on their knuckles, that means
osteoarthritis is at least partly a metabolic problem, and has nothing to do
with stresses and loads.

It is known also that IL6 induces the liver to make CRP, and the heavy
modulation of IL6 by energy restriction has long been known in animals. CRP
also makes macrophages make nitric oxide and a lot of other inflammatory and
perhaps nasty chemicals. Statin drugs themselves are modest
antiinflammatories, and also anticarcinogens in many systems. It would not
be surprising if statin drugs were better at correcting inflammation in
obese people, but so far as I can tell, this has not been specifically
tested (there's an idea for somebody).

Perhaps CRP will prove to be a causal factor in both atherosclerosis AND
some other degenerative processes of aging in humans. We're naturally
interested in what causes CRP levels to drop in humans. Weight loss does, at
least if we believe epidemiologic trials plus one small prospective weight
loss trial (see below). The "statin" drug atorvastatin/Lipitor does (see
abstract), and the drop of 0.8 in the study is significant in light of the
fact that CRP levels below 1 are considered "low" risk, and above 2
"moderate risk."  Also the combination of niacin and lovastatin decreases
CRP in a dose-dependent manner (not clear if the niacin is helping, but
probably). Statins are presently the only class of drugs which has been
proven to extend life in a subset of humans (people with coronary risk
factors) who are even reasonable proximate stand-ins for the average person.
I know of no life-span studies of statins on rodents, perhaps because nobody
thought to do them, since rodents don't get atherosclerosis and coronary
disease. But with the new connection of inflammation, CRP, statins, and
aging, it may be a better idea to test statins on rodents in a full-on life
span study, than we had thought. Hmmm. You read it here first.

One last comment of interest on a trifle: Some years ago I had the chance to
go through data from the China Health Study, a gigantic study of
prospective lab tests and later disease and death in some hundreds of
thousands of Chinese. One of the fascinating effects noted is that there is
no effect of LDL levels on heart disease at the cholesterol levels common in
rural China (cholesterol about 125 mg/dl), but there is a marked effect of
very low cholesterol levels (less than 90 or so) on death by infectious
disease-primarily pneumonia. Very low levels of LDL are bad. I had assumed
that they were merely a marker for malnutrition, which in turn subjected
people to higher risk of infections. But perhaps not. In the interview
below, one of the factors reported to contribute to the research was the
fact that "Recently, the Witztum team found that many mouse antibodies that
are specific to oxidized LDL are identical to "T15" type natural antibodies
that have been extensively studied for 30 years by immunologists for their
recognition of S. pneumoniae, the most common cause of pneumonia. T15 also
binds to phosphocholine present on pathogens and provides a protective
immune defense against those pathogens." So there you are: if you have a lot
of oxidized LDL perhaps this causes your levels of antibodies to this rise,
and these protect you, in turn, from strep pneumonia. This feeds a bit into
my long suspicion that the systems which protects you from infection may
well be the ones that later cause degeneration and aging, and there is only
a limited amount that can be done with them in the real and dirty world.
Most calorie restriction experiments, remember, have been done in
semi-isolated laboratories.

Steve Harris, MD

News and abstracts:

The following news release and any accompanying images can be accessed on
the web at:

Contact: Sue Pondrom (619) 543-6163 at SCSD

News Date: September 9, 2002

Team Identifies Potential Role of CRP In Development of Atherosclerosis

Another piece of the complex puzzle of how inflammation is involved in heart
attacks and strokes has been discovered by researchers at the University of
California, San Diego (UCSD) School of Medicine.

Their findings demonstrate that C-reactive protein (CRP) binds to oxidized
low density lipoprotein (LDL), implicating the interaction of CRP and
oxidized LDL as a potential trigger for the cascade of events leading to
atherosclerosis. This form of artery disease is characterized by the buildup
of fatty deposits and chronic inflammation along the artery wall, eventually
leading to heart attack. Published in the online edition of Proceedings of
the National Academy of Sciences (PNAS) the week of Sept. 9, 2002, the study
by the UCSD researchers pinpoints how CRP attaches itself to oxidized LDL,
the so-called "bad cholesterol" that accumulates in the artery wall and
generates atherosclerotic plaques. LDL is the major cholesterol carrying
particles. When they enter the artery wall from the circulation, they are
believed to be modified by oxidation. It is this "oxidized LDL" that is
thought to be the culprit leading to inflammation and cholesterol
accumulation. "Our study points out that CRP is not merely a marker of
future cardiovascular events, as most people believe, but it actually binds
to oxidized LDL and apoptotic or dying cells, giving it a potential role in
development or modulation of atherosclerosis, as well as in other
inflammatory disease," said Mi-Kyung Chang, M.D., an assistant project
scientist and the first author of the paper in PNAS. In the new studies, the
UCSD team showed that CRP binds to oxidized LDL through the recognition of
phosphocholine, a part of an oxidized molecule on the surface that is
exposed when LDL undergoes oxidation.

Noting that there is an accumulation of dead and dying cells (apoptotic
cells) in atherosclerotic lesions and that these cells are under increased
oxidative stress, the UCSD researchers also determined that CRP binds to
these cells in a similar manner as it recognizes oxidized LDL. CRP is
conventionally regarded as a first-line defense of the immune system against
invading pathogens and confers protection to humans by removing pathogens.
Recently, CRP has been reported as a useful marker for predicting future
atherosclerotic cardiovascular events, but the basis for this correlation
remains unclear.

Although scientists still do not understand all the steps in the development
of atherosclerosis, it is known that oxidized LDL in the artery wall are
taken up (engulfed) by macrophages, scavenger cells that have been drawn to
the site by oxidized LDL. When they become engorged with the oxidized LDL,
the macrophages become "foam cells," the hallmark of atherosclerotic
plaques. It is possible that CRP may bind to oxidized LDL and further
enhance the uptake into cells.The paper's senior author, Joseph Witztum,
M.D., professor of medicine, added that cholesterol is still a key player in
coronary heart disease. He said that CRP may be working in its "correct
role" as part of the immune response to the toxic oxidized LDL and may help
promote its clearance. "If you have low levels of LDL, and thus, low levels
of oxidized LDL, then CRP may be of benefit," Witztum said. "However, when
there is an overwhelming accumulation of LDL, and thus oxidized LDL, in its
attempt to help clear the toxic particle, the CRP may actually make things
worse. It may cause more oxidized LDL to be taken up into macrophage
scavenger cells, which in turn cause cholesterol accumulation a sort of
'Trojan horse'." For the past 20 years, the Witztum lab at UCSD, in
collaboration with UCSD professor of medicine Daniel Steinberg, M.D., Ph.D.,
has pioneered the role of oxidized LDL as a major contributing factor for
the development of atherosclerosis. In particular, the Witztum lab has been
studying immunological response to oxidized LDL and its impact on
development and modulation of atherosclerosis. Recently, the Witztum team
found that many mouse antibodies that are specific to oxidized LDL are
identical to "T15" type natural antibodies that have been extensively
studied for 30 years by immunologists for their recognition of S.
pneumoniae, the most common cause of pneumonia. T15 also binds to
phosphocholine present on pathogens and provides a protective immune defense
against those pathogens.As both T15 antibody and CRP recognize the same
molecule, phosphocholine, Chang reasoned that CRP might bind to oxidized
LDL, but not native LDL that does not expose phosphocholine. Indeed, Chang
and colleagues showed that CRP does bind to oxidized LDL as well as
apoptotic cells through the recognition of phosphocholine. Therefore, CRP is
now a novel immune response to oxidized LDL, along with macrophages and T15
antibodies, through the recognition of the same phosphocholine molecule,
which is also present on many infectious pathogens. Studies are now underway
to determine whether CRP is protective, or could actually cause harm.

The UCSD research was funded by the National Institutes of Health. In
addition to Chang and Witztum, additional authors were Christoph J. Binder,
Ph.D., post doctoral fellow, and Michael Torzewski, M.D., visiting scholar,
UCSD Department of Medicine.


J Nutr Biochem  2002 Jun;13(6):316-321

C-reactive protein and coronary artery disease: influence of obesity,
caloric restriction and weight loss.

Heilbronn LK, Clifton PM.

CSIRO Health Sciences and Nutrition, Adelaide, SA 5000, Australia

C reactive protein (CRP) values in blood are a good indicator of the
likelihood of acute coronary and cerebral events in both healthy subjects
and patients with coronary artery disease. This indicates that
atherosclerotic lesions rich in inflammatory cells and cytokines are more
likely to produce acute events either through vasospasm and/or thrombosis
and also can be readily detected through elevations in CRP when measured
using a high sensitivity assay (hsCRP).  However the arterial wall is
only one potential source of cytokines which induce CRP production. Fat
cells also produce cytokines, in particular IL-6 which induces the
synthesis of CRP by the liver. Obesity, especially abdominal obesity, is
associated with elevations of hsCRP. This may be of pathogenic
significance as CRP stimulates the uptake of LDL by macrophages, induces
complement activation which may cause cellular damage in the artery, and
enhances monocyte production of tissue factor, thus enhancing the risk of
thrombosis. Caloric restriction and weight loss lowers IL-6 and CRP
levels and may beneficially suppress an immune response. Whether
particular dietary macronutrients or micronutrients alter IL-6 or CRP is
unknown but this issue is clearly becoming more important.

PMID: 12088796 [PubMed - as supplied by publisher]

Circulation  2002 Feb 5;105(5):564-9
Comment in:
 Circulation. 2002 Feb 5;105(5):E9071-2.
Weight loss reduces C-reactive protein levels in obese postmenopausal women.

Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET.

Department of Medicine, College of Medicine, University of Vermont,

BACKGROUND: C-reactive protein (CRP) has been proposed as an independent
risk factor for cardiovascular disease and has been positively associated
with body weight and body fatness. We examined the hypothesis that weight
loss would reduce plasma CRP levels in obese postmenopausal women.
METHODS AND RESULTS:  In a sample of 61 obese (body mass index, 35.6 +/-
5.0 kg/m(2)), postmenopausal women (age, 56.4 +/- 5.2 years), we found
that plasma CRP levels were positively associated with dual x-ray
absorptiometry-measured total body fatness (r=0.36, P<0.005) and
CT-measured intra-abdominal body fat area (r=0.30, P<0.02).  Significant
correlations were also found between plasma CRP and triglyceride levels
(r=0.33, P<0.009) and glucose disposal measured by the
hyperinsulinemic-euglycemic clamp technique (r=-0.29, P<0.03).
Twenty-five of the 61 women tested at baseline completed a weight loss
protocol. The average weight loss was 14.5 +/- 6.2 kg (-15.6%, P<0.0001),
with losses of 10.4 +/- 5.4 kg fat mass (-25.0%, P<0.0001) and 2.8 +/-
1.4 kg fat-free mass (-6.0%, P<0.0001). Visceral and subcutaneous fat
areas were reduced by -36.4% and -23.7%, respectively (P<0.0001). Plasma
CRP levels were significantly reduced by weight loss: average -32.3%,
from 3.06 (+0.69, -1.29) to 1.63 (+0.70, -0.75) microgram/mL (P<0.0001,
medians and interquartile differences). Changes in body weight and in
total body fat mass were both positively associated with plasma CRP level
reductions. CONCLUSIONS: Adiposity was a significant predictor of plasma
CRP in postmenopausal women on a cross-sectional basis. Moreover, caloric
restriction-induced weight loss decreased plasma CRP levels. Weight loss
may represent an important intervention to reduce CRP levels, which may
mediate part of its cardioprotective effects in obese postmenopausal

Publication Types:
Clinical Trial

PMID: 11827920 [PubMed - indexed for MEDLINE]

Clin Chem 2002 Jun;48(6 Pt 1):877-83
Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive
protein concentrations in individuals with visceral obesity.

Chan DC, Watts GF, Barrett PH, Beilin LJ, Mori TA.

University Department of Medicine, University of Western Australia and the
Western Australia Institute for Medical Research, Royal Perth Hospital,
Perth, Western Australia WA 6847, Australia.

BACKGROUND: Chronic low-grade inflammation may contribute to the increased
risk of atherosclerosis in visceral obesity. Statin and fish oil have been
reported to have antiinflammatory effects. We studied whether dyslipidemic,
obese individuals have increased plasma high-sensitivity C-reactive protein
(hs-CRP) concentrations and whether treatment with atorvastatin and fish oil
lowered plasma hs-CRP concentrations. METHODS: We compared plasma hs-CRP,
interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)
concentrations in 48 obese individuals with the concentrations in 10 lean
normolipidemic men. The obese individuals were then randomized to treatment
with atorvastatin (40 mg/day), fish oil (4 g/day), atorvastatin plus fish
oil, or matching placebo for 6 weeks. RESULTS: Compared with controls, obese
individuals had increased hs-CRP [geometric mean, 2.19 mg/L (95% confidence
interval, 2.15-3.15 mg/L) vs 0.49 mg/L (0.30- 0.93 mg/L); P <0.001] and IL-6
[351 pg/L (318-449 pg/L) vs 251 pg/L (211-305 pg/L); P <0.01]. Atorvastatin
treatment had a significant main effect of decreasing plasma hs-CRP (-0.87
mg/L; 95% confidence interval, -0.10 to -1.60 mg/L; P <0.01) and IL-6 (-70
pg/L; 10 to -140 pg/L; P <0.01), but this was not seen with fish oil. The
reductions in hs-CRP with atorvastatin were not significantly correlated to
changes in plasma lipids, IL-6, insulin resistance, or cholesterogenesis.
Plasma TNF-alpha concentrations in obese individuals, however, were neither
statistically different from concentrations in the lean controls nor altered
with atorvastatin or fish oil treatment. CONCLUSIONS: This study shows that
visceral obesity is associated with increased plasma hs-CRP and IL-6 and,
hence, a low-grade chronic inflammatory state and that treatment with
atorvastatin or atorvastatin with fish oil, but not fish oil alone, reverses
this abnormality.

Publication Types: Clinical Trial Randomized Controlled Trial
PMID: 12029003 [PubMed - indexed for MEDLINE]

Ann N Y Acad Sci  2001 Apr;928:327-35
The inflammation hypothesis of aging: molecular modulation by calorie
Chung HY, Kim HJ, Kim JW, Yu BP.

Department of Pharmacy, College of Pharmacy, Research Institute of Genetic
Engineering, Pusan National University, Korea.

Current evidence strongly indicates that reactive oxygen species (ROS)
and reactive nitrogen species (RNS) are widely implicated in the
inflammatory process. However, mechanistic information is not readily
available on the extent to which ROS/RNS contributes to the
proinflammatory states of the aging process.  The involvement of the
underlying inflammation during the aging process and the molecular
delineation of anti-inflammatory action of calorie restriction (CR) is
described. Age-related upregulations of NF-kappaB, IL-beta, IL-6,
TNFalpha, cyclooxygenase-2, and inducible NO synthase are all attenuated
by CR. The suppression of the NF-kappaB activation was accomplished by
blocking the dissociation of inhibitory IkappaBalpha and IkappaBbeta by
CR. These findings provide underlying molecular insights into the
anti-inflammatory action of CR in relation to the aging process. Based on
these and other available data, it is suggested that the "Inflammation
Hypothesis of Aging" supports the molecular basis of the inflammatory
process as a plausible cause of the aging process.

Publication Types:
Review, Tutorial

PMID: 11795524 [PubMed - indexed for MEDLINE]

Mech Ageing Dev  1997 Feb;93(1-3):87-94

Calorie restriction inhibits the age-related dysregulation of the cytokines
TNF-alpha and IL-6 in C3B10RF1 mice.
Spaulding CC, Walford RL, Effros RB.
Department of Pathology and Laboratory medicine, University of California
School of Medicine, Los Angeles 90095-1732, USA.

TNF-alpha and IL-6 are generally increased in the sera of aged humans and
mice.  The dysregulation of these cytokines may be critical in
autoreactivity and immune dysfunction. In earlier studies we demonstrated
that production of TNF-alpha and IL-6 following in vitro stimulation of
peritoneal macrophages by LPS was reduced in old compared to young mice,
and that dietary caloric restriction (CR) had no effect on the induction
of TNF-alpha in this system.  In the present study we examined the
effects of age and calorie restriction on the constitutive production of
both TNF-alpha and IL-6. Serum levels of both cytokines were
significantly higher in old versus young mice. However, in old mice
subjected to long term CR the serum levels were comparable to those of
young mice. The potential involvement of normalization of TNF-alpha and
IL-6 levels in the life extension effect of CR are discussed.

PMID: 9089573 [PubMed - indexed for MEDLINE]

I welcome email from any being clever enough to fix my address. It's open
book.  A prize to the first spambot that passes my Turing test.

From: "Steve Harris" <>
Subject: Re: News on C-rective Protein and LDL, with notes by S. Harris
Message-ID: <sW7h9.1226$>
Date: Sun, 15 Sep 2002 22:35:04 GMT

galya wrote in message <>...
>Well done, thank you for your efforts and sharing your thoughts(a
>keeper post for sure)!!!
>Some more about statins:
>Article #1 reports about the first study to suggest that statins
>(in-vitro)suppress T-cells activation.
>Article #2 is the most recent one on the subject still only talking
>about the "scientific rationale for suggesting the use of statins as
>novel immunosuppressors, not only in organ transplantation but in
>numerous other pathologies as well." :-(
>Article # 3 suggests that Lovastatin reduces risk of cancer.
>Isn't it time to sell them OTC with Co-Q10 (you mentioned Co-Q10
>Any comments?


Yes, they should be OTC, and in some sense are already. You can buy red rice
yeast pills OTC now. These have natural lovastatin (called "mevinolin" as a
natural product, in amounts sufficient to significantly lower cholesterol if
you take a couple of grams a day of extract. This yeast which makes the
statin also provides the red coloring for a lot of Chinese dishes (the red
of a Peking Duck!) and it's where the statins were discovered originally.
Heck, if it weren't for AIDS and a few other problems where people need all
the helper T-cell activity they can get, I'd be suggesting that statins be
added, in fat Western cultures, to cholesterol raising foods! They certainly
have the potential to be a major weapon in our obese sat and trans fat
intoxicated, bloated society. Alas, trans fats practically just about ARE
everywhere in every processed food and anything with milk fat, and your tax
dollars support the sales of the big saturated fat killers (your fed income
tax pays for the those beef and whole milk commercials on TV). And you pay
again when medicare pays for bypasses, but not for statins. Dumb, dumb,
dumb, *criminally* dumb federal policy. Statins are the closest thing to a
life-extension drug pill ever invented, but they are $100 a month, and only
a small fraction of people who could be befitting from them, are taking

I'm personally also incensed about the fibrate drugs (Tricor/ fenofibrate
and the older Lopid/gemfibrozil), which may be keeping needy people from
getting a statin, by fixing numbers instead of the disease. These drugs
*suck* as a class-- they may lower chance of an MI by a small amount, but
nothing like what is suggested by their cholesterol effect, and they haven't
been shown to increase life span-- probably because what they give in
decreased cholesterol, they take away in cancer risk. Indeed, there is
reasonable evidence that they CAUSE GI cancer. Yech.  But many a dollar
which should be spent on statins is wasted here. Similar comments apply to
cholesterol-lowering bile acid binding agents (cholestyramine and
colestipol). Niacin is a much better second-line drug.

I'll drink menhaden
Oil and take a statin
Pill or two.
And add an aspirin to
The brew.

You can't be half-assed
Avoiding bypass
It fries your brain, you see--

[Again, appologies to Larry Hart]

Steve Harris, MD

I welcome email from any being clever enough to fix my address. It's open
book.  A prize to the first spambot that passes my Turing test.

From: "Steve Harris" <>
Subject: Re: inflammation
Message-ID: <9m8h9.1280$>
Date: Sun, 15 Sep 2002 23:04:37 GMT

Carey Gregory wrote in message ...
>ironjustice@aol.comdoe (doe) wrote:
>>When one eats a high fat meal .. which leads to thick blood .. one gets
>Says who?
>>I would bet dollars to donuts if one 'thins the blood' .. inflammation
>>would go down.
>I'll take that bet.  How many dollars?

Indeed a bad bet. A high fat meal influences clotting, but I don't know of
any evidence that it does much for systemic inflammation, at least in the
short term.

By the way, in my last post I suggested that obesity's effect on CRP might
be responsible for its effect as an independent cardiac risk factor (we know
part of the obesity effect is independent of cholesterol), but I'm sorry if
I went too far and looked like I was saying this was the entire mechanism.
It certainly isn't. For example, there is evidence that ALL of obesity's
effect cannot be mediated by CRP or anything else we have so far discovered.
Obesity is known to influence vascular endothelial function (a nitric oxide
mediated step which is also screwed up by smoking) and this is almost
certainly one of the ways that being viscerally fat contributes to getting a
heart attack. BUT we have yet to discover the mechanism, except that it
isn't CRP, post prandial lipemia, or any of the other traditional risk
factors. It's something as yet unknown...

Just to remind everyone of how far we are from having all the answers, even
in the case of a disease like heart disease, where after years of study we
do know SOME of the answers.

Am J Cardiol  2001 Dec 1;88(11):1264-9
Usefulness of visceral obesity (waist/hip ratio) in predicting vascular
endothelial function in healthy overweight adults.
Brook RD, Bard RL, Rubenfire M, Ridker PM, Rajagopalan S.
Division of Hypertension, University of Michigan, Ann Arbor, Michigan, USA.

Vascular endothelial dysfunction (VED) is associated with obesity;
however, its etiology remains controversial. By determining the
predictors of fasting and postprandial endothelial function in overweight
adults without other cardiovascular risk factors, we were able to
investigate novel mechanisms directly linking obesity to VED. Thirty-two
healthy adults (body mass index [BMI] > or =27 kg/m(2)) underwent
determination of fasting low-density lipoprotein (LDL) particle size,
high sensitivity C-reactive protein levels, anthropometric measurements,
and endothelial function by flow-mediated dilation (FMD) of the brachial
artery. Postprandial lipemia and FMD were measured 4 hours after
ingestion of a high-fat meal. Blood pressures and fasting levels of
lipoproteins, glucose, insulin, and fatty acids were within normal limits
in all subjects. An abdominal fat pattern, as determined by an increased
waist/hip ratio (WHR), was the sole significant predictor of FMD (r =
-0.58, p = 0.001), despite no significant correlation between whole body
obesity (BMI) and FMD.  At comparable levels of BMI, obese subjects with
a WHR > or =0.85 had a significantly blunted FMD compared with those with
a WHR <0.85 (3.93 +/- 2.85% vs 8.34 +/- 5.47%, p = 0.016). Traditional
coronary risk factors, C-reactive protein, postprandial lipemia, and LDL
particle size did not predict FMD. We found no appreciable alteration in
the postprandial state from fasting FMD (6.31 +/- 4.62% vs 6.25 +/-
5.47%, p = 0.95). The same results were found when women were analyzed
alone. Increased abdominal adiposity determined by a simple WHR is a
strong independent predictor of VED even in healthy overweight adults;
this is a finding unexplained by alterations in conventional risk
factors, systemic inflammation, or the atherogenic lipoprotein pattern.

PMID: 11728354 [PubMed - indexed for MEDLINE]

I welcome email from any being clever enough to fix my address. It's open
book.  A prize to the first spambot that passes my Turing test.

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