Aspirin resistance in cardiovascular disease
BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39405.635498.80 (Published 24 January 2008) Cite this as: BMJ 2008;336:166
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According to the “BMJ : What’s new on line,” of Jan 23,2008,
editorials discussed, “Aspirin resistance in cardiovascular disease, “
and, “The cardiovascular risks of calcium supplements in women.”
Probably as a lack of appreciation of the pathophysiological
significance of altered blood rheology, it seems not to be recognised that
key factors in both situations are increased blood viscosity and reduced
red cell deformability, both of which may be worsened by treatment.
According to Ajmani and Rifkind (1), the aging process is associated
with reduced red cell deformability and increased blood viscosity, with
raised levels of fibrinogen increasing plasma viscosity. They noted,
“ It has been found in a number of clinical observations for various
groups of patients and in case-control studies that the rheological
properties of the red cell change in the course of aging.” This could
relate to changes in the shape populations of red cells as Simpson and
O’Neill (2) reported that immediately fixed blood samples from 76 males
and 91 females aged between 60 and 96 years, showed a prevalence of non-
discocytic cells with flat cells being the most common change, when
studied by scanning electron microscopy. As change in the internal
environment stimulates change in the shape populations of red cells, this
could reflect the age-related changes in the composition of blood.
As non-discocytic red cells are poorly deformable and contribute to
blood viscosity, it should be noted that there are many reports concerning
the increased blood viscosity which has been found in association with
cardiovascular disorders. Therefore it seems possible that “aspirin
resistance,” might become explicable in terms of blood viscosity and/or
reduced red cell deformability, drawing attention to the possibility of
other treatment options.
Ajmani and Rifkind (1) discussed the studies of the effects of
menopausal changes on blood rheology, which showed changes in the
composition of the blood with increased fibrinogen levels as a major
feature. They stated, “ Elevated blood viscosity factors for
postmenopausal women are indicative of a high risk of cardiovascular
mortality.” As calcium has been shown to stiffen red cells, calcium
supplements would amplify the effects of poorly deformable red cells, and
increase the possibility of an adverse event in postmenopausal women.
The apparent failure to recognise the relevance of blood rheology in
both editorials, draws attention to a paper by Professor John Dormandy
(3), who organised the Second European Conference on Clinical
Haemorheology under the auspices of the Royal Society of Medicine. In
1982 he stated, “ …practising clinicians have tended to be unjustifiably
resistant to new ideas. The continuing collaboration between
haemorheologists and clinicians, which was the theme of this Conference,
is the essential next step in establishing clinical haemorheology in its
proper place.”
It should be a major concern that the “essential next step” has not
been taken, and the published information concerning altered blood
rheology in the major causes of morbidity and mortality, cardiovascular
disorders, cerebrovascular disease and stroke, diabetes, hypertension
etc., has failed to gain clinical recognition. As the first review on
blood viscosity was published in 1911, surely it is time to recognise the
clinical significance of the topic.
Les Simpson (retired experimental pathologist)
Dunedin, New Zealand.
References.
1. Ajmani RS, Rifkind JM. Hemorheological changes during human
aging. Gerontology 1998;44: 111-20.
2. Simpson LO, O’Neill DJ. Red cell shape changes in the blood of
people 60 years of age and older imply a role for blood rheology in the
aging process. Gerontology 2003;49:310-5.
3. Dormandy JA. Second European Conference on Clinical
Haemorheology. J Roy Soc Med 1982;75:581-3.
Competing interests:
None declared
Competing interests: No competing interests
Aspirin resistance in cardiovascular disease: Muddy waters?
We read with interest the editorial article on Aspirin “resistance”
in cardiovascular disease by Professor Biondi-Zoccai and Marzia Lotrionte.
The authors state that clopidogrel should be substituted for aspirin, for
people at intermediate thrombotic risk and low risk of bleeding, as a more
effective alternative. Given the observed significant heterogeneity in the
subgroup analysis from CAPRIE, we contend that clopidogrel and aspirin are
only equivalent in efficacy in patients suffering a myocardial infarction
and that Clopidogrel is not superior.
We agree with the authors that Aspirin resistance may be a
reflection of the normal variability to drug response however the issue of
patient concordance with therapy must be a paramount concern . Medication
concordance data in transplant patients demonstrates that up to a third
of patients do not adhere to their prescribed regimen.
Finally, we agree that the underlying issue may well be that drug regime
in most cases assumes a “one size fits all” approach, but switching to a
different medication may result in a similar phenomenon. More clinical
trials with other drugs therefore, may only serve to muddy the waters.
1. Caprie steering committee. A randomised, blinded, trial of
clopidogrel versus aspirin in patients at risk of ischaemic events
(CAPRIE). Lancet 1996; 348: 1329 – 39
2. M Dew, A Di Martini, A De Vito Dabbs, L Myaskovsky, J Steel, M Unruh, C
Switzer, R Zomak, R Kormos and J Greenhouse. Rates and risk factors for
nonadherence to the medical regimen after adult solid organ
transplantation. Transplantation 2007 ; 83 (7) : 858-873
Competing interests:
None declared
Competing interests: No competing interests