Wolf-Rdiger Schbitz and Holger Reinecke

Hemorrhagic Stroke?
Chronic Kidney Disease and Alcohol Consumption: Are Asians at Particular Risk for
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doi: 10.1161/STROKEAHA.111.626713
2011;42:2385-2386; originally published online August 18, 2011; Stroke.
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Chronic Kidney Disease and Alcohol Consumption
Are Asians at Particular Risk for Hemorrhagic Stroke?
Wolf-Rudiger Schabitz, MD; Holger Reinecke, MD
See related article, pages 25312537.
S
troke represents one of the major challenges of the 21
st
century. More than 15 million people suffer from stroke
each year worldwide. Enormous efforts in public awareness
and prevention of the disease have led in industrialized
countries to a slightly declining incidence. Mortality and
morbidity (measured in disability-adjusted life years) are,
however, expected to rise substantially during the next 2
decades; stroke will climb from 8th rank in 2010 to the 5th
rank in 2030 worldwide; compared with 1990, the disability-
adjusted life years attributed to stroke will nearly double over
these 40 years.
1
One important comorbidity that dramatically influences
stroke and its outcome is chronic kidney disease (CKD), a
clearly underestimated cardiocerebrovascular risk factor.
CKD is defined as the combination of kidney damage (with
albuminuria) and reduced glomerular filtration rate, as esti-
mated from serum creatinine levels.
2
The prevalence of CKD
is substantially and/or continuously increasing, from 10% to
13.1% during the last decade (US National Health and
Nutrition Examination Survey).
2
Currently, more than 20
million Americans are affected by this disease, many of them
not even aware of it. Preventing and treating CKD was
therefore declared a global challenge.
3
In addition to the fact
that such a substantial number of people are affected and may
finally require renal replacement therapy or transplantation,
even more important is that CKD dramatically drives cardio-
cerebrovascular morbidity and mortality.
24
CKD is highly associated with important stroke risk factors
such as hypertension, diabetes, myocardial hypertrophy, and
atrial fibrillation.
4
Apart from these, CKD is associated with
a number of disturbances in hemostasis and was found to be
an independent risk factor of cardiocerebrovascular events.
Consequently, risk of stroke in CKD patients was signifi-
cantly higher than in those without CKD.
4
Once a stroke in
these patients occurred, it appeared to be a grave prognosis:
the little existing data reported 2-year mortality rates of 74%
in patients with end-stage renal failure, and even 55% in a
combined subgroup with earlier stages of CKD.
4
Dr. Shimizu and colleagues add in this issue of Stroke
5
some important aspects to the currently very rare data set on
CKD and stroke. The authors identified in a prospective
cohort of 11780 Japanese men and women without previous
cardiovascular disease the estimated glomerular filtration rate
(eGFR) as the main factor driving stroke risk in men and
women. The total occurrence of strokes in patients with a
normal eGFR (89 mL/min) was 4.3% in men, and 2.4% in
women. With a declining eGFR (60 mL/min, to be classi-
fied as CKD stages 35), stroke increased markedly to 13.1%
in men and 7.6% in women. Even in the subgroup with an
eGFR between 90 and 60 mL/min (mild renal failure, to be
classified as CKD stage 2) a clear, but not significant, trend
for higher stroke rates could be seen in both men and women
(6.7 and 3.6%, respectively). As seen in other cardiovascular
complications and events, we have to be aware that CKD
increases the risk for both ischemic and hemorrhagic strokes
already in early stages, with an eGFR 90 mL/min, and
significantly below 60 mL/min, respectively.
The most interesting finding of the present study is the
association between alcohol drinking habits, CKD, and oc-
currence of hemorrhagic strokes. A particular strength of the
study is the documentation of stroke subtype by brain
imaging (MRI or CT) in 93% of stroke patients. Whereas
rates of hemorrhagic strokes were very similar in men and
women without CKD (0.61.5%, respectively) regardless of
whether they were drinkers, men and women with CKD
suffered from a markedly higher rate of hemorrhagic strokes
when drinking alcohol (5.3% and 6.1%, respectively) com-
pared with never-drinkers with CKD (0.7% and 1.7%, respec-
tively) and those without CKD. This is important and sug-
gests a recapitulation: drinking in the present study was
defined as consumption of 0.3 go or more per week (1 go, is
a traditional Japanese unit of volume equal to 23 g of ethanol,
2 glasses of wine, 1 bottle of beer, or 75 mL whisky).
Although this is substantially lower than the current accepted
recommendation of alcohol per day for cardiocerebrovascular
protection, in patients with CKD, it led to more brain
hemorrhages in this study. A potential reason for the finding
could be the decreased activity of the alcohol dehydrogenase
in this Japanese population that may have increased alcohol
toxicity in the brain much more than in a comparable white
population. Although this is a speculation, if just a part of
these findings were true, it would have an enormous impact
on current recommendations and guidelines. Of note, about
78% of men and 12% of women in this Japanese cohort were
current or former drinkers according to this definition. One
conclusion from the present study could therefore be a strict
alcohol prohibition in at least all Asian patients with eGFR
60 mL/min.
Received June 24, 2011; accepted June 24, 2011.
The opinions in this editorial are not necessarily those of the editors or
of the American Heart Association.
From the Department of Neurology Bethel (W.-R.S.) EVKB, and the
Department of Cardiology and Angiology (H.R.), University Hospital of
Munster, Munster, Germany.
Correspondence to Holger Reinecke, MD, Department of Cardiology
and Angiology, University Hospital of Munster, Albert-Schweitzer-Str.
33, 48129 Munster, Germany. E-mail holger.reinecke@ukmuenster.de
(Stroke. 2011;42:2385-2386.)
2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.111.626713
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A bit surprising in the present analysis was that the rate of
ischemic strokes in men was not significantly different
between distinct subgroups with CKD. However, because the
time of occurrence of strokes was not reported, it could
simply be that in this cohort with 78% currently or formerly
drinking men, hemorrhagic stroke was the overriding and
early determining factor. In comparison, in women the higher
stroke rates in advanced stages of CKD were mainly because
of the marked increase in ischemic strokes (whereas the
increase in hemorrhagic stroke rates with a decline in eGFR
was not significant).
We understand that each study has its particular focus and
cannot answer all questions. However, apart from aforemen-
tioned interesting and novel findings, the study has also
weaknesses. It is well known that stroke is tightly correlated
with atrial fibrillation, particularly in CKD patients.
4
The low
incidence of atrial fibrillation in the present study (56
patients0.4% of the cohort) is surprising and might be
confounded by a lack of systematic screening for atrial
fibrillation in the study design. One may argue that study
patients were rather young, with average ages between 50 and
60 years, but associated comorbitidies such as diabetes,
hypertension, and especially CKD were as frequent as in
other studies with higher rates of atrial fibrillation. Overall, it
is unexpected und not plausible that atrial fibrillation could
here not be identified as a risk factor for the occurrence of
ischemic strokes in men and women. Lack of data assessment
continues in anticoagulation regimens with oral anticoagula-
tion or antiplatelet drugs that were not recorded, but may have
influenced total stroke rate, and particularly influenced hem-
orrhagic strokes.
In summary, this work shows that CKD is an independent
risk factor for higher stroke rates in men and women.
Although moderate alcohol consumption is widely accepted
to have protective effects against cardiocerebrovascular
events, it appears in this Japanese cohort to be harmful in
patients with CKD because it caused many more brain
hemorrhages. This finding is clearly important, impacts
current recommendations and guidelines of stroke care, and
definitely requires more investigations. A direct and reason-
able conclusion might be a strict alcohol prohibition in Asian
patients with an eGFR 60 mL/min.
Disclosures
None.
References
1. WHO in collaboration with the US Centers for Disease Control and
Prevention. The Atlas of Heart Disease and Stroke. http://www.who.int/
cardiovascular_diseases/resources/atlas/en/.
2. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al.
Prevalence of chronic kidney disease in the United States. JAMA. 2007;
298:20382047.
3. Meguid El, Nahas A, Bello AK. Chronic kidney disease: the global
challenge. Lancet. 2005;365:331340.
4. Reinecke H, Brand E, Mesters R, Schabitz WR, Fisher M, Pavenstadt H,
et al. Dilemmas in the management of atrial fibrillation in chronic kidney
disease. J Am Soc Nephrol. 2009;20:705711.
5. Shimizu Y, Kenji Maeda K, Imano H, Ohira T, Kitamura A, Kiyama M, et
al. Chronic kidney disease and drinking status in relation to risk of stroke
and its subtypes; the Circulatory Risk in Communities Study. Stroke.
2011;42:25312537.
KEY WORDS: alcohol

Hemorrah

Intrac.

chronic kidney disease
2386 Stroke September 2011
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