Inflammation in Vascular Disease
There has been a relatively sudden paradigm shift in cardiovascular medicine
from fat-based theories of arterial disease toward recognition of the pervasive
role of inflammation. Inflammation is a fundamental pattern of immune response.
Teague et al wrote:” Cardiovascular disease (CVD) remains the leading cause of
death worldwide, highlighting the need to elucidate its pathogenesis. Once
considered a passive biological process, CVD is now recognized as an active,
immune-driven process that may begin in childhood. Current research into the
natural history of atheroma development has implicated many immune cells,
including phagocytes, lymphocytes, dendritic cells, and neutrophils. Because
these cells play a major role in initiating plaque development and complication,
leukocytes are promising targets for acute and chronic atherosclerosis therapy.
The most numerous cells in atherosclerotic plaques are macrophages, leukocytes
that are central to innate immunity. In atherosclerosis, macrophage accumulation
commences as bone marrow–derived, high monocytes infiltrate the lesion.
Chronic inflammation may arise from food, infection, and autoimmune disease. I
have yet to meet a cardiologist who knows that food antigens, such as cow’s milk
proteins, can trigger inflammatory disease. Delayed patterns of food allergy may
cause inflammation in vessel walls and trigger the clotting mechanism. Keaney et
al reported that: “Background Inflammation within vulnerable coronary plaques
may cause unstable angina by promoting rupture and erosion. In unstable angina,
activated leukocytes may be found in peripheral and coronary sinus blood.”
The mechanisms of arterial disease appear to be multiple. Hollander of Boston
University suggested that atherosclerosis was an autoimmune disorder with immune
complexes injuring blood vessel walls. We think that circulating immune
complexes contain a variety of chemicals some airborne may are in the food
supply. Food proteins act as antigens and cause a wide spectrum of food allergic disease. Since proteins
derived from meat, milk, eggs and wheat have the highest risk of appearing in
the blood as immune complexes, these foods are reduced or eliminated in the
Alpha Nutrition Program.
We ask a simple question - If there is any possibility that chronic
symptoms such as attacks of migraine, heart rhythm abnormalities, digestive
disturbances, breathing difficulties or brain dysfunction are linked to food
ingestion, would it not be prudent to investigate and remove food -causes using
diet revision as an inexpensive, safe, effective strategy? Protein antigens,
arriving in the blood through the digestive tract may trigger an immune response
that inflames and damages the arterial walls. Many people with delayed pattern
food allergy develop migraine, angina, heart rhythm abnormalities and may be
more likely to develop blood clots and inflammation of blood vessel walls, all
features of the life-threatening complex of vascular disease.
Keaney et al reported that:” background Inflammation within vulnerable
coronary plaques may cause unstable angina by promoting rupture and erosion. In
unstable angina, activated leukocytes may be found in peripheral and
coronary-sinus blood. “
A non-specific indicator of inflammation is the C-reactive protein levels in
the blood. Elevated levels are associated with increased risk of heart attacks
and strokes. For example, Ridker et al studied 27,939 apparently healthy
American women, who were followed for eight years for the occurrence of
myocardial infarction, ischemic stroke, coronary revascularization, or death
from cardiovascular causes. Elevated C-reactive protein levels were a better
predictor of vascular events than low LDL cholesterol levels. The researchers
reported that: ” 77 percent of all events occurred among women with LDL
cholesterol levels below 160 mg per deciliter (4.14 mmol per liter), and 46
percent occurred among those with LDL cholesterol levels below 130 mg per
deciliter (3.36 mmol per liter)… C-reactive protein and LDL cholesterol
measurements tended to identify different high-risk groups, screening for both
biologic markers provided better prognostic information than screening for
Myeloperoxidase is another serum marker of inflammation that may be
Myeloperoxidase is an enzyme that generates reactive oxygen species, is released
from white blood cells. In one study, plasma myeloperoxidase levels were
predictive of subsequent coronary events in patients with chest pain.
Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform,
and C-reactive protein levels, identified patients at risk for cardiac events in
the absence of myocardial necrosis.“
Circulating Immune Complexes
Immune complexes are formed when antibody binds to antigen, usually a protein.
Circulating complexes (CIC), distributed in the blood, are formed in a variety
of circumstances and may trigger illness by a variety of mechanisms. The
pathogenic significance of complexes depends on the antibody involved, the
relative concentration of antibody and antigen, the distribution of complexes
and the ability of the host to clear them. CICs play a pathogenic role variety
of disease states including arthritis, polymyositis, vasculitis,
glomerulonephritis, hemolytic anemia, leucopenia, and thrombocytopenia. They are
found in infectious diseases, autoimmune diseases, following organ transplants,
and in patients with food allergy.
Antibody excess tends to favor rapid
clearing of complexes. Antigen excess favors complexes that stay longer in the
circulation. Medium sized complexes tend to be more pathogenic and tend to get
deposited in tissues. Tissue ICs can be identified by immunofluorescent staining
of biopsy specimens. Serum IC measurements are neither easy nor reliable
indicators of disease activity. Meaningful CIC measurement would have to be
carried out in a physiological manner - for example tracking in real time the
serum and tissue concentrations of ICs following antigen challenge. Spot samples
of serum CIC concentration will not yield very useful information.
Pirquet first described serum sickness, a prototype of immune complex disease.
Any antigen entering the circulation in sufficient quantity can produce symptom
patterns resembling serum sickness. The most direct model of food allergy
involves free antigen entering the circulation and complexing with antibody to
form circulating immune complexes (CICs). Immune complexes may form in the gut
submucosa and may be transported by lymphatic channels to regional nodes and may
continue through to the thoracic duct to enter the systemic circulation. Serum
sickness evolves over a period of 7-10 days after a discrete antigen challenge.
Manifestations include general malaise, fever, flushing, sweating, hives,
swelling, bruising, joint and muscle pain, progressing in the worst case to
inflammatory disease in target organs with protein in the urine from kidney
inflammation. In animals, a large single intravenous dose of bovine milk protein
will induce serum sickness with vasculitis and glomerulonephritis. Immune
complexes are present from day 5 through 13.
Inflammation can be treated by removing the causes of inflammation, treating
infection and using anti-inflammatory medication such as ASA. The role of food
proteins and immune complexes as agents of inflammation is rarely investigated
and may turn out to be the hidden agent behind many heart attacks and strokes.
Keaney, J. F. Jr., Vita, J. A. (2002). The Value of Inflammation for
Predicting Unstable Angina. N Engl J Med 347: 55-57
Paul M. Ridker, M.D., Nader Rifai, Ph.D., Lynda Rose, M.S., Julie E. Buring,
Sc.D., and Nancy R. Cook, Sc.D. Comparison of C-Reactive Protein and Low-Density
Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular Events.
NEJM Volume 347:1557-1565 November 14, 2002 Number 20
Marie-Luise Brennan, Ph.D., Marc S. Penn, M.D., Ph.D., Frederick Van Lente,
Ph.D., et al Prognostic Value of Myeloperoxidase in Patients with Chest Pain
NEJM Volume 349:1595-1604 October 23, 2003