CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 4, July/August 2011
AFRICA
223
Obesity and platelet reactivity: the relationship remains uncertain
Two recent studies on obesity have sought
to provide clarity to the hypothesis that
increasing BMI could be associated with
high on-treatment platelet reactivity.
These studies were undertaken in differ-
ent populations.
The first study was undertaken in
251 patients undergoing elective PCI
who were given dual antiplatelet therapy
(clopidogrel and aspirin). Their platelet
reactivity was measured six to 24 hours
after PCI and any relationship with obesi-
ty was examined.
1
The second study was undertaken as
part of the Genetic STudy of Aspirin
Responsiveness (GeneSTAR), which was
designed to examine the genetic determi-
nants of platelet responsiveness to low-
dose aspirin.
2
This latter population of
healthy at-risk-by-family-history cohort
included 2 014 participants who were
given low-dose aspirin (81-mg aspirin
tablet) for 14 days. Platelet-function tests
were performed at baseline and after 14
days.
The PCI study undertaken at the
Washington Hospital Centre found no
association between BMI and platelet
reactivity, as quantified by a variety of
platelet-function tests (LTA: light trans-
mission aggregometry, VASP: vasodila-
tor-stimulated phosphoprotein phospho-
rylation, P2y12 and Verify now aspirin
assays).
The baseline characteristics of the
obese patients in this study were generally
similar to those of the non-obese patients.
Obese patients’BMI was defined as above
30 kg/m
2
. Patients were mainly male and
25% were African-American.
All patients received a 600-mg loading
dose of clopidogrel six hours before plate-
let-reactivity testing or a 75-mg mainte-
nance dose for more than five days before
testing. Aspirin therapy was 325 mg six to
24 hours before platelet-reactivity testing.
The results show that all five platelet-
reactivity tests were not normally distrib-
uted, but using Spearman co-efficient
and scatter plots, there was a very poor
correlation between BMI and platelet
reactivity. Using definitions specific to
each test, there was still no statistically
significant association with BMI. Only
chronic renal insufficiency was associat-
ed with high on-treatment platelet reactiv-
ity. The authors concluded that their study
does not support an approach that would
modify antiplatelet therapy of clopidogrel
and aspirin in obese patients.
In the population of higher-risk but
healthy family members of whom docu-
mented CAD events occurred in close
family members before 60 years of age,
the baseline characteristics of the obese
and non-obese groups were different.
Obese individuals were older, female and
black, and less likely to smoke cigarettes.
Platelet-function tests were performed
at baseline and after 14 days of regu-
lar non-enteric aspirin therapy (81 mg).
Platelet reactivity was determined by
platelet count, aggregometry (same test
as in the first study) and plasma fibrino-
gen. Aspirin assays were not performed as
the tests of inhibition of the COX-1 path-
way (AA aggregation and Tx-M: urinary
excretion of 11-dehydro-thromboxane
B2) were performed.
The study found that obese individu-
als demonstrated greater
ex vivo
platelet
activation in response to all agonists,
including collagen, ADP and AA.
In vivo
platelet activation measured by Tx-M
was also greater in the obese participants.
Most measures were statistically signifi-
cant or near significant between the obese
and non-obese groups.
Platelet reactivity following aspirin
In assays directly related to the COX-1
pathway (e.g. AA aggregation and Tx-M),
obese individuals consistently showed
greater residual platelet reactivity (meas-
ured in ohms) than non-obese individuals
after aspirin. Similarly, a significantly
larger fraction of obese individuals had
any residual platelet reactivity to AA
(measured in percentage non-zero aggre-
gation) after aspirin than non-obese indi-
viduals. Tx-M was suppressed in both
groups with aspirin, but obese individu-
als demonstrated greater
in vivo
platelet
reactivity after aspirin compared with
non-obese individuals. A higher percent-
age of obese individuals met the Tx-M
criteria (upper quartile) for aspirin resist-
ance following aspirin.
Similar to the direct COX-1 pathway,
indirect COX-1 pathways (i.e. aggrega-
tion to collagen and ADP) also showed
significantly greater residual platelet
reactivity after aspirin in obese than in
non-obese individuals. For collagen and
Tx-M, the absolute change in platelet
activation was the same or greater in
obese persons compared with the non-
obese, while for ADP-induced platelet
aggregation, there was a small increase.
A BMI cut off of 30 kg/m
2
was chosen
because there was a non-linear relation-
ship between BMI and platelet reactivity
that appeared at a BMI of 29.8 kg/m
2
.
Similar results were obtained using waist
circumference instead of BMI, but the
relationship was not as strong.
In a very small sub-group (106
patients), a further aspirin dose of 325
mg/day was given for an additional 14
days, followed by platelet-function tests.
The larger aspirin dose did not result in
any further decrease in platelet activation.
The authors concluded that obese
individuals had greater baseline plate-
let function than non-obese patients,
which suggests that while obese patients
obtained a similar effect with low-dose
aspirin, it may not have been sufficient
to overcome their higher levels of native
platelet activation. Further studies are
needed to determine the clinical conse-
quences of these observations in both
epidemiological and clinical settings.
J Aalbers, Special Assignments Editor
1.
Gaglia MA, Torguson R, Pakala R, Xue Z,
Sardi G, Mahmoudi M,
et al
. Relation of
body mass index to on-treatment (clopidog-
rel + aspirin) platelet reactivity.
Am J Cardiol
2011. DOI: 10.1016/j.amjcard.2011.04.029
2.
Bordeax BC, Qayyum R, Yanek LR, Vaiya
D, Becker LC, Faraday N,
et al
. Effect of
obesity on platelet reactivity and response
to low-dose aspirin. Clinical study.
Prevent
Cardiol
2009. DOI: 10.1111/j.1751-
7141.2009.00058.x.
