Omega-3
Fatty Acids for the Prevention and Treatment of Atherosclerotic
Diseases
By
Morten Bryhn, MD, Ph D
4/15/2003
No organism with a high metabolic
rate like that of vertebrates can grow beyond a volume of
a few cubic millimetres without developing a functional
circulatory system. This is because simple diffusion cannot
supply the requisite respiratory, nutritional and excretory
exchanges between the interior of the tissue mass and its
surface. It is not surprising that the cardiovascular system
is the first organ of an embryo to reach a functional state.
Circulation of the blood has started by the beginning of
the fourth week. At that stage the sitting height of the
embryo is about 5 mm. A functional anatomy is clearly distinguishable.
Circulatory
insufficiency is the number one cause of deaths in the industrialized
world and has been so since 1918. So circulation of blood
is where it all starts and where it ends. Recent statistics
from the US tells us that life expectancy would rise by
7 years, from today’s 77 years, if all forms of major
cardio vascular diseases (CVD) were eliminated. For comparison
the gain would be only 3 years if all forms of cancer were
abolished (1). The main cause of CVD is atherosclerosis;
an inflammatory and degenerative disease of the arteries
caused by aging, heritage, and well defined risk factors
leading to restricted circulation of arterial blood. Risk
factor intervention, dietary measures, certain drugs, and
even surgical procedures may positively influence clinical
features of atherosclerosis, mainly myocardial infarction
and stroke. Atherosclerosis is a dynamic disease with a
progressive pattern and clinical data clearly indicate that
proper measures may postpone the development of arterial
narrowing and obliteration of blood flow related to this
disease.
Atherosclerosis
has previously been described as a straight “plumbing
problem” with fat-laden debris gradually building
up on the internal surface of artery walls. If a deposit
or plaque grew large enough, it eventually closed off the
affected “pipe,” preventing the blood from reaching
its intended tissue. The plaques could be large or small,
the large plaques easily spotted on an angiogram while the
small largely left undetected were being considered harmless.
The large plaques may change the blood flow pattern by a
gradual increment of the arterial l lumen, but it is the
small plaques that are the malignant ones prone to burst
suddenly and start a cascade of events leading to a thrombus,
obliterating the coronary or cerebral artery flow creating
a myocardial infarction or stroke (2).
Fig. 1
The
small, vulnerable plaques contain lipid pools and inflammatory
cells covered by a thin inflamed fibrous cap (3, Fig.1).
Activated by cytokines, both inflammatory cells and smooth
muscle cells produce matrix-degrading metalloproteinases
that weaken the fibrous cap, increasing the risk of bursting
(4, Fig.2). The change of paradigm from a “plumbing
problem” to a dynamic, inflammatory process which
may be altered by immunosuppressive measures, is new opening
up new possibilities for prevention as well as treatment
of CVD.
Fig. 2
Prevention
of CVD is based on risk factor reduction and certain pharmaceuticals,
such as aspirin and cholesterol lowering drugs. But even
the inflammatory process should be addressed. Nature’s
own way of suppressing the immunological response to activation
are the omega-3 fatty acids being the starting material
for production of local acting hormones suppressing immunological
actions. Omega-3 fatty acids are therefore frequently used
for treatment of autoimmune diseases such as rheumatic disease.
People with a high intake of omega-3 fatty acids through
fish and sea mammals do not develop atherosclerosis to the
same extend and at the same age as people who do not. The
immunosuppressive effects of omega-3 fatty acids may explain
this.
Newman
and colleagues examined two groups of inhabitants from Alaska
dead from non-CVD causes, for the presence of atherosclerosis:
natives and non-native immigrants, mainly Caucasians, Asian
and Hispanic (5). Fat tissue, abdominal aorta and coronary
arteries were sent to New Orleans and analysed without knowledge
from which group the specimen came from. The fat tissue
concentrations of omega-3 fatty acids eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA) were much higher in
the natives indicating a high intake of fatty seafood. Surface
involvement with atherosclerosis was very different between
the groups: Aorta as well as the coronary arteries from
natives had significantly less atherosclerosis compared
to the none-natives. A typical picture of aorta from one
of each group is shown in
Surface
involvement of the aorta related to age groups shown in
Fig. 3 demonstrates that there was about 10 years delay
in the native group with high EPA and DHA in their fat tissue
for equal development of atherosclerosis compared to the
non-native group. It seems that the formation of atherosclerosis
was prevented as a function of high intake of omega-3 fatty
acids.
Fig. 3
The
study by Newman and colleagues is interesting but there
are lots of confounding factors not counted for in this
epidemiologic study. Therefore, the therapeutic principle
was tested in a controlled clinical study in patients with
atherosclerotic plaques of the neck arteries (6). The patients
on a waiting list for operation were randomly allocated
to treatment with EPA/DHA omega-3 fatty acids, sunflower
oil or placebo. After an average treatment time of 42 days
the atherosclerotic plaques were removed an analysed with
respect to the content of EPA/DHA, plaque morphology and
immunological activation. The plaques from the omega-3 treated
group had significantly higher content of EPA/DHA and the
plaques were more often organised and not so often of the
soft type prone to rupture. In the other two groups plaques
were more often of the vulnerable type with thin, fibrous
caps with significant signs of inflammation (Fig. 4).
Fig. 4
Interestingly
the degree of vulnerability could be significantly altered
after on average 6 weeks of treatment underlining the dynamic
pattern of atherosclerotic plaques and the potent actions
of omega-3 fatty acids to stabilise plaques. Admitted omega-3
fatty acids lower elevated blood pressure, have beneficial
effects on blood lipids and reduce thrombadhesion as well
but usually interventions on these mechanisms with pharmaceuticals
takes years to demonstrate in trials enrolling thousands
of patients. The anti-inflammatory effects of EPA/DHA seems
to offer a very potent and effective means of preventing
and treating atherosclerotic diseases as an ideal combination
to a standard risk reduction regimen.
REFERENCES
1)
Heart disease and stroke statistics. American Heart Association,
2003:1-42
2)
van Belle E. et al. Coronary angioscopic findings in the
infarct-related vessel within 1 month of acute myocardial
infarction Circulation 1998; 97:26-33
3)
Libby P. et al. Macrophages and atherosclerotic plaque stability
Current Opinion in Lipidology 1996; 7:330-335
4)
Ganz P et al. Pathogenetic mechanisms of atherosclerosis:
effect of lipid lowering on the biology of atherosclerosis
Am J Med 1996; 101(suppl 4A): 10S-16S
5)
Newman WP, Middaugh JP, Pedersen HS, et al. Atherosclerosis
in arctic populations: autopsy studies. Prevention and treatment
in vascular disease. Springer Verlag 1995:77-84
6)
Thies F, Garry JM, Yacoob P, et al. Association of n-3 polyunsaturated
fatty acids with stability of atherosclerotic plaques: a
randomized controlled trial. Lancet 2003; 361:477-485
back
to top
|
