Views & Reviews From the Frontline

Vascular disease: an amateur observation

BMJ 2010; 341 doi: (Published 22 September 2010) Cite this as: BMJ 2010;341:c5196

Infections, lipoproteins and homocysteine in vascular disease

More than a hundred reviews have been published about the association
between microorganisms and cardiovascular disease, but almost all authors
consider their presence as a secondary phenomenon. Des Spence, who
describes himself as an amateur, is one of the few today who has realised
that microorganisms have a causal role.1 This view was accepted one
hundred years ago by William Osler and his contemporaries.2 As Klotz and
Manning expressed it, "There is every indication that the production of
tissue in the intima is the result of a direct irritation of that tissue
by the presence of infection or toxins."3

There is much evidence that the micro-organisms are more than
innocent bystanders. We have recently presented a detailed report about
this issue including a new hypothesis which explains how vulnerable
plaques are created.4 The following is a short summary of our

The clinical picture of an acute myocardial infarction is similar to
that of an infection: slight fever, diaphoresis, leucocytosis and in
severe cases, bacteraemia and sepsis. Serological markers of infections,
bacteraemia and periodontal infections are risk markers for cardiovascular
disease. Cardiovascular mortality increases during epidemics, and about a
third of all such patients have had an infectious diseases immediately
before the vascular attack. That preventive measures by antibiotics have
had little effect is not contradictory to microbial etiology, since
remnants of more than fifty different bacteria and viruses have been found
in atherosclerotic plaques. It is very unlikely that a short treatment
with a single antibiotic should be able to prevent repeated vascular
attacks. Treatment of ongoing periodontal infections has been succesful,
however, in diminishing the carotid arterial wall thickness to a greater
extent than seen in any cholesterol-lowering trial.5

That the decline in vascular deaths from 1950 onwards mirrors the
decline in infectious disease 40 years earlier is in accordance with the
microbial etiology of vascular disease. In 1904 Thayer found a high
frequency of arterial lesions in patients who died from typhoid fever and
a high prevalence of arteriosclerotic radial arteries in those who
survived.6 Liuba and his group found that infections in early life are a
risk factor for vascular disease. They studied infected children by high-
resolution ultrasound and demonstrated narrowing of the coronary arteries
in those who died from the infection, and thickening of the carotid intima
-media in those who survived.7,8

Few medical observers know that the plasma lipoproteins participate
in the immune system by binding and inactivating most microorganisms and
their toxic products.4,9 This important function of lipoproteins has been
demonstrated repeatedly by different investigators during the last 70
years. We believe that blockage of arterial vasa vasorum with endothelial
dysfunction by complexes composed of lipoproteins, microorganisms,
endotoxins, homocysteinylated LDL and various autoantibodies creates local
hypoxia of the arterial wall. This process leads to creation of a
vulnerable plaque, named by Osler as an "atherosclerotic pustule," and
when the pustule bursts, thrombosis occurs, producing acute coronary
syndrome, stroke or gangrene.


1. Spence D. Vascular disease: an amateur observation. BMJ 2010;
341:c5196. Osler W. Diseases of the arteries. In: Modern Medicine: its
Practice and Theory (Osler W, Ed), Lea & Febiger, Philadelphia, 1908,
pp 426-447.

2. Osler W. Diseases of the arteries. In: Modern Medicine: its
Practice and Theory (Osler W, Ed), Lea & Febiger, Philadelphia, 1908,
pp 426-447.

3. Klotz O, Manning MF. Fatty streaks in the intima of arteries. J
Pathol Bacteriol 1911;16:211-220.

4. Ravnskov U, McCully KS. Vulnerable plaque formation from
obstruction of vasa vasorum by homocysteinylated and oxidized lipoprotein
aggregates complexed with microbial remnants and LDL autoantibodies. Ann
Clin Lab Sci 2009;39:3-16.

5. Piconi S, Trabattoni D, Luraghi C, Perilli E, Borelli M, Pacei M,
et al. Treatment of periodontal disease result in imporvements in
endothelial dysfuncton and reduction of the carotid intima-media
thickness. FASEB J. 2009;23:1196-1204.

6. Thayer WS. On the cardiac and vascular complications and sequels
of typhoid fever. Bull Johns Hopkins Hosp 1904; Oct:323-340.

7. Pesonen E. Infection and intimal thickening: evidence from
coronary arteries in children. Eur Heart J. 1994;15 Suppl C:57- 61.

8. Liuba P, Persson J, Luoma J, Yla-Herttuala S, Pesonen E. Acute
infections in children are accompanied by oxidative modifi- cation of LDL
and decrease of HDL cholesterol, and are followed by thickening of carotid
intima-media. Eur Heart J. 2003;24:515-521.

9. Han R. Plasma lipoproteins are important components of the immune
system. Microbiol Immunol 2010; 54: 246-253.

Competing interests: No competing interests

20 October 2010
Uffe Ravnskov
Independent investigator
Kilmer S. McCully
Magle Stora Kyrkogata 9, 22350 Lund and Pathology and Laboratory Medicine Service, VA Boston Healthc
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