COFFEE AND TEA CONSUMPTION AND RISK OF STROKE

SUBTYPES IN MALE SMOKERS

Name : Angeline Tancherla Tutor : dr. Janet
NIM : 01071170034

1. Description of Place Person Time

Place Person Time
 Finnish Male Smokers
 Aged 50 to 69 years
Finland 1985-December 2004
 Without history of stroke at baseline
 Tea and Coffee drinkers

2. Hypothesis : Coffee and Tea Consumption Will Reduce the Risk of Stroke Subtypes in
Male Smokers

3. Find the best possible Association :

a) Chance (Yes/No)
Explanation :
The association of coffee and tea consumption with risk of stroke subtypes is not by
chance. This is because there were other similar studies conducted that had given the
same result as the hypothesis in this study. In a prospective study of Finnish patients,
those who consumed more than 3 cups of coffee per day had 27% lower risk of stroke
than those who consumed less than 3 cups per day. However, in contrast, another
study conducted in US among male non-smokers had different results from the
hypothesis above. This may be because the lack of number of cases in the study and
also difference of study populations between smokers and non-smokers. Meanwhile,
the association of tea consumption and risk of stroke had consistent results. It is stated
in the Zutphen study, conducted with 552 Dutch men followed over 15 years, that the
high consumption of tea could decrease the risk of stroke. Aside from that, there were
also two prospective cohort studies that had proven green tea consumption could
significantly reduce the risk of stroke. The first cohort was conducted among Japanese
women and was followed up for 4 years. And they found out that women, who
consumed less than 5 cups of tea per day, were more likely to develop risk of stroke
 for about twice higher than those who consumed more than 5 cups per day. The other
cohort, conducted among 40 530 Japanese men and women followed up for 11 years,
concluded that green tea consumption has a relation of being protective (RR=0.49,
which is less than 1) towards cerebral infarction mortality. From those studies, we can
be assured that the findings of the study are consistent, which makes it unlikely to
happen coincidentally.

b) Bias (Yes/No)
Explanation :
It is possible that bias may happen in the study. The study design is a cohort study,
which means the researchers had to do a long period of follow-up. The mean follow-
up is 13.6 years, which is a very long time and the researchers may not be able to
follow-up until the end of study. Therefore, loss of follow-up may happen. While
answering the validated food-frequency questionnaire at baseline, the subjects may
remember incorrectly the amount of daily coffee and tea consumption, and would
result to recall bias. Plus, they might not know exactly how many mL they've been
drinking daily, and they might be answering the questionnaires carelessly. There were
only 3 sizes of cups given in the questionnaire (for coffee 70 mL, 110 mL, and 170
mL; and for tea 110 mL, 170 mL, and 220 mL). The subjects may not have exact
same consumption that matches to the given cup sizes. As a result, they might answer
it according to the closest amount of cup sizes. And this could lead to measurement
bias. In addition, the amount of coffee and tea consumption was only collected once at
baseline. There may be changes of amount of coffee and tea consumption that may
alter the result of the study. However, there is no possibility that selection bias may
happen, due to the randomized selection of subjects and double blinding in the ATBC
study.

c) Confounding (Yes/No)
Explanation :
There is no possibility of having a confounding factor. This is because the potential
risk factors have been adjusted in the study. In the main multivariate models, smoking
(number of cigarettes smoked per day), BMI, systolic and diastolic blood pressure,
serum total cholesterol, serum HDL cholesterol, histories of diabetes and coronary
heart disease, leisure-time physical activity, and alcohol intake were further adjusted.
 These adjustments also include adjustment for age, supplementation group, and
cardiovascular risk factors. In addition, adjustment for diet as confounder had also
been done. The consumption of fruits, vegetables, fish, and total fat did not
significantly alter the results for coffee (highest versus lowest category: RR, 0.78;
95% CI, 0.66 to 0.90) or tea (corresponding RR, 0.82; 95% CI, 0.70 to 0.95). Similar
results were acquired when the participants who developed acute myocardial
infarction or diabetes during follow-up were censored. Moreover, the observed
relationships were consistent within different subgroups. We can observe the data in
Table 4, the inverse association between coffee consumption and risk of cerebral
infarction was consistent in subgroup analysis according to history of diabetes,
coronary heart disease, systolic and diastolic blood pressure, alcohol intake, and
cigarettes smoked per day. Similarly, the inverse association between tea consumption
and cerebral infarction did not vary significantly by age, cardiovascular risk factors,
or supplementation group. This further supports the idea that confounding by those
factors was unlikely to explain the results. In order to check if there is any
confounding factor due to increased of exposure misclassification over time, the
follow-up time was divided into less than 10 years and 10 or more years of follow-up.
And the results also did not vary significantly. Thereby, the association between
coffee and tea consumption and risk of cerebral infarction is not due to confounding.

d) Reverse Time Order (Yes/No)

Explanation :
It is clearly illogical and impossible that the lower risk of stroke would be causing
people to consume more coffee and tea. There is no logical association of the order
and it is not biologically reasonable. Moreover, the observed study is a cohort study,
in which exposure was measured before there is outcome. Therefore, the correct time
order is that the risk of stroke subtypes would be decreased after high consumption of
coffee and tea in a period of time.

e) Causal (Yes/No)
1) Strength of Association
The strength of association is strong. This is because the relative risks obtained from
heavy coffee drinkers and tea consumption are less than 1, which significantly
showed that the coffee and tea consumption is protective for risk of stroke. It
 suggests that coffee and tea consumption decreased the risk of cerebral infarction,
which is a stroke subtype. The p value for the association of coffee and tea
consumption with the risk of cerebral infarction are respectively <0.001 and 0.02.
The confidence intervals obtained are also narrow. This shows that coffee and tea
drinking is highly correlated to lower the risk of cerebral infarction. Furthermore,
the risk of cerebral infarction of subjects who consumed more than 8 cups of coffee
per day and 2 or more cups of tea per day have been lowered by 23% and 21%,
compared to subjects with no or low consumption of coffee and tea. While in
distinction, the results didn't show a significant protective effect of coffee and tea
consumption with intracerebral hemorrhage and subarachnoid hemorrhage, because
the relative risks are not significant and the p values are more than 0.05.

2) Consistent
The findings of the study are consistent even if observed in different people, places
and time. As I have explained before, there were other studies conducted and they
had the same result with this study. It is stated in the Finnish study, the high
consumption of coffee could decrease the risk of stroke by 27%. In the Zutphen
study, it was concluded that high consumption of tea is significantly associated to
lowered risk of stroke. Aside from that, there were also two prospective cohort
studies in Japan that had proven green tea consumption could significantly reduce
the risk of stroke. The first cohort found out that women, who consumed less than 5
cups of tea per day, were more likely to develop risk of stroke for about twice higher
than those who consumed more than 5 cups per day. The other concluded that green
tea consumption has a relation of being protective towards cerebral infarction
mortality.

3) Specificity
The association between the exposure and effect is not specific in this study.
Because, the exposure, which is coffee and tea consumption, may lead to other
effects. Coffee and tea may also prevent liver disease and cancer, decrease the risk
of dementia and lower the risk of type 2 diabetes. Therefore, there is no one to one
or a specific relationship between cause and outcome. But since diseases may have
many causes; and exposures may cause multiple effects, specificity is a weaker
 criterion in determining causality. Thus, specificity has value in specific causation
when it is present, but a lack of specificity does not imply lack of causation.

4) Temporality
This study fulfills the temporality criteria, which means the cause occurred after the
exposure. In this study, it is concluded that high consumption of coffee and tea
precedes the reduced risk of cerebral infarction. On top of that, the cohort study had
measured the exposure before there is an outcome.

5) Dose Response
According to the data table of the study, the increase of coffee and tea consumption
leads to the lower risk of cerebral infarction. We can know by analyzing the relative
risk. The relative risk gets lower as the coffee and tea consumption is increased.
They were respectively decreased by about 0.1-0.2, compared to low or no
consumption of coffee and tea. This means that the more coffee and tea
consumption, the more likely a person would have lower risk of cerebral infarction.
We can also observe from the graph (in Figure) that the spline regression analysis
demonstrated a dose-response relationship between coffee consumption and risk of
cerebral infarction.

6) Biological Plausibility
The association of coffee and tea consumption and reduced risk of cerebral
infarction is biologically plausible due to the phenolic compounds in coffee and tea.
Polyphenols found in tea have antioxidant activities and prevent oxidation of low
density lipoprotein (LDL) cholesterol in vitro and in vivo. Oxidization of LDL
particles gives rise to the formation of atherosclerotic lesions, leading to increased
risk of cardiovascular disease that may cause stroke. Furthermore, daily
supplementation of α-tocopherol suggestively reduced the risk of cerebral infarction,
as stated from the ATBC study. However, this dietary antioxidant had no effect on
intracerebral hemorrhage and had increased the risk of subarachnoid hemorrhage.
This is because ischemic stroke (such as cerebral infarction) and hemorrhagic stroke
are of different causes. Ischemic stroke occurs when a blood vessel (artery)
supplying blood to an area of the brain is blocked. The blocked blood flow in an
ischemic stroke may be caused by a blood clot or by atherosclerosis. While
 hemorrhagic stroke occurs when a blood vessel in your brain leaks or ruptures. The
most common cause is aneurysm. An aneurysm occurs when a section of a blood
vessel becomes enlarged from chronic and dangerously high blood pressure or when
a blood vessel wall is weak. A rarer cause of an ICH is an arteriovenous
malformation (AVM). This occurs when arteries and veins are connected
abnormally without capillaries between them, which is usually congenital. Evidence
from observational studies suggests that coffee drinking is inversely associated with
inflammation and endothelial dysfunction. Endothelial dysfunction is a fundamental
step in the atherosclerotic disease process that is linked to ischemic stroke. It has
been observed in stroke patients and has been related to stroke physiopathology,
stroke subtypes, clinical severity and outcome. Coffee consumption may decrease
postprandial hyperglycemia, improve insulin sensitivity and reduce the risk of type 2
diabetes. In a recent large cohort study, type 2 diabetes was associated with an
increased risk of ischemic stroke but not hemorrhagic stroke. In addition, from a
recent randomized control trial, black tea consumption in men was found to be a
factor that could reduce platelet activation and plasma C-reactive protein (a marker
of systemic inflammation). In prospective studies, high blood concentrations of C-
reactive protein have associated with an increased incidence of ischemic stroke,
including cerebral infarction. Therefore, we can conclude that coffee and tea play a
role in reducing the risk of cerebral infarction.

7) Coherence
The association does not conflict with what is known about the natural history,
biology and previously reported evidence of stroke. There are numerous examples of
studies with different designs and populations that successfully identify the same
relationship between an coffee and tea consumption with the reduced risk of stroke
subtypes. For example, like the Finnish study, Zutphen study and the 2 Japanese
studies. Therefore, it meets the coherency criteria.

8) Experimental Evidence
There were no experimental evidences, because the study only evaluated the
associations of coffee and tea consumption with the risk of stroke subtypes in the
ATBC Study cohort. No experimental studies were done. The researchers only
observed and followed-up the coffee and tea consumption in relation to the reduced
 risk of stroke subtypes among the subjects. There is no intervention, as they didn't
assign the amount consumption of coffee and tea in subjects.

9) Analogy
There were no studies suggestive of a 'direct' causal association via a similar agent.
But there were experimental evidence in rats studies that had shown coffee could
improve glucose metabolism and may reduce the risk of diabetes, which is a risk
factor for stroke. Aside from that, there were also in vitro and in vivo experiments
that proved polyphenols in tea have antioxidant activities and could prevent
oxidation of low density lipoprotein (LDL) cholesterol, which is also a risk factor
for stroke.

4. The most possible Association : Causal

The most possible association is causal because the study meets most (7 out of 9) of the
Hills criteria in determining the causality of the association of coffee and tea
consumption with the lowered risk of stroke subtypes (cerebral infarction). Although
bias may be a possible association, but it is considered weak. Therefore, being stronger,
causal is the most possible association.

5. 2 Prevention/Policy to prevent the disease/outcome.

 Stroke happens when blood supply to the brain is cut off. This could happen due to
the blockage or bursting of arteries. There are several factors that could cause stroke.
The very common cause is atherosclerosis, which is the blockage of arteries due to
fats. And so, a very simple and practical prevention of stroke is to have a healthy
diet. Eating foods with less fats and cholesterol can help reduce the risk of
atherosclerosis. Aside from that, hypertension can also lead to stroke. To maintain
normal blood pressure, it is important to control diet. Therefore, we can start a
campaign to advertise the benefits of healthy diet and to prevent stroke. We can give
informations about foods that may cause or may prevent stroke. We can also share
tips on how to eat healthily, for example:
 Reduce the salt in your diet to no more than 1,500 milligrams a day (about a half
teaspoon).
  Avoid high-cholesterol foods, such as burgers, cheese, and ice cream.
 Eat 4 to 5 cups of fruits and vegetables every day, one serving of fish two to three
times a week, and several daily servings of whole grains and low-fat dairy.

 And by having a healthy diet, you could also lose weight. Obesity is significantly
associated to cause stroke. Because obesity is also linked to high blood pressure,
diabetes, and many other cardiovascular diseases. Along with having a healthy diet, it
is also helpful if you exercise often. Exercising could burn fats and keep your heart,
lungs, and circulatory system healthy. We can make a crusade against stroke by
having morning exercises at neighbourhoods. These exercises are aimed for elder
people, because they are less active and have high risk of stroke. And by exercising
daily, the people could reduce and prevent having stroke.

6. Prevention for Bias in the study

• Avoid loss of follow up
• Set up strict guidelines for data collection
• Improve questionnaire design
• Use automated measuring devices
• Measure risk factor several times
• Shorten the interval between data collection