METHODOLOGY RESEARCH

THE RELATIONSHIP OF DRINKING BEER

AND CORONARY ARTERY DISEASE
IN MEN AGED 30 TO 40 YEARS OLD.
(Spira Penta Orbis 9th Nov 2011)

GROUP 1
NAME
Fawza Nabila Faudzi
Ahmad Farhan Hasbi
Mohamad Luqman Hadi bin Ismail
Mohamad Fareez Hairi Mohd Saupi
Gadis M.P Randa
Luke Michael
Miftah Farid Asmaun
Ahmad NurFakhri

NIM
C11110858
C11110869
C11110880
C11110846
C11110801
C11110835
C11110812
C11110823

METHODOLOGY RESEARCH, DEPT OF PATHOLOGY ANATOMY

FACULTY OF MEDICINE
UNIVERSITY OF HASANUDDIN
2011

RESEARCH TITLE:

THE RELATIONSHIP OF DRINKING BEER AND CORONARY

ARTERY DISEASE
IN MEN AGED 30 TO 40 YEARS OLD.
RESEARCH QUESTIONS:
1. What is the importance of this research study?
2. What is the effect of drinking beer to coronary artery disease?
3. Is there any difference between low/moderate beer drinker and high beer
drinker towards risk of coronary artery disease?
4. What are the contents of beer that can cause coronary artery disease?
5. What is coronary artery disease?
6. Is there any scientific evidence to prove this research study?
FOX LION PHENOMENON:
The fox: Amount of beer consumed per day
The lion: Hypertension, Diabetes, Dyslipidemia, Smoking
In our research study, the lion will be chased out as this will affect the
final results of our research study.
VARIABLES:
a) Independent variable
: Amount of beer consumed per day
b) Dependent variable : Risk of coronary artery disease (CAD)
c) Controlled variable
: Hypertension, Diabetes, Dyslipidemia, Smoking
(EXCLUDE)
EXCLUSION AND INCLUSION CRITERIA:
a) Inclusion criteria
: We only include samples that are men and their age
is between 30 to
40 years old.
b) Exclusion criteria
: Exclusion criteria is the confounding factor. In this
case, the confounding
factor or the thing that should be
exclude are samples that smoking,
samples that have
diabetes, samples that have dyslipidemia and
samples that have hypertension. The major risk factors of CAD are high
level LDL in blood, hypertension, smoking and
others.1 So, if we do not
exclude these factors, it will affect
the final results of this research study.

1 S.GORINSTEIN et al. Moderate beer consumption and the blood coagulation in

patients with coronary artery disease. Journal of Internal Medicine 241: 47-51, 1997

OPERATIONAL DEFINITION
a) Heavy beer drinker
Heavy drinking indicates usual intake of more than 3 drinks per day of wine,
liquor or beer. In absolute terms, amount of pure alcohol consumed
>30g/day are considered as heavy drinking 2
b) Moderate beer drinker
The recommended daily limits for moderate alcohol consumption are no
more than two drinks for men or one drink for women per day 3
c) Coronary artery disease (CAD)
Risk of coronary artery disease is measured using exercise cardiac stress test
(ECST).A positive
test was defined as horizontal and segmental ST depression or elevation of 0.1 mV

.4

2 DHARAM PA. Cardioprotective Effects of Light Moderate Consumption of Alcohol:

A Review of Putative Mechanisms. Alcohol & Alcoholism 37: 409-415, 2002
3 U.S. Department of Health & Human Services National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism, 2006. Young Adult Drinking.
4 ALAN GB, VICTOR SB, ROBERT HP, EDWARD SO, YIHONG K: Graded Exercise Stress
Tests in Angiographically Documented Coronary Artery Disease. Circulation 49: 348356, 1974

SPIRAL PENTA ORBIS APPROACH

1. Construct Conceptual Writing Framework

High beer drinking

(>3 glass/day)

Coronary Artery
Disease
(CAD)

2. Explore the Dynamic Potential of Each Variable

Beer
a) Beer contains alcohol
Whenever available, we extracted information on amount of alcohol
consumed, using grams of alcohol per day as the common unit of measure.
When a study did not specifically report the grams of alcohol per unit, we
used 12.5 g/drink for analysis. We standardized portions as a 12 oz (355ml)
bottle or can of beer, a 5 oz (148 ml) glass of wine, and 1.5 oz (44 ml) glass
of 80 proof (40% alcohol) distilled spirits. Volume of intake was categorized
as <2.5 g/day (<0.5 drink), 2.514.9 g/day (about 0.51 drink), 1529.9
g/day (about 12.5 drinks), 3060 g/day (about 2.55 drinks), and >60 g/day
(5 drinks).5
Alcohol content of different beer styles6
Description
Amount
Alcohol

Amount containing 80g

5 PAUL ER, SUSAN EB, BARBARA JT, KENNETH JM, WILLIAM AG. Association of alcohol
consumption with selectedcardiovascular disease outcomes: a systematic review and metaanalysis. British Medical Journal 2011;342:d671.

6 MICHAEL GM: Alcohol and coronary heart disease. International Journal of

Epidemiology 30: 724-729, 2001

Draught bitter
Draught
ale,
mild

pint
pint

(g)
8.7
7.4

alcohol (approx)
5 pints
5 pints

b) Beer contains maltose

Data from Buckee and Hargitt state that beer contains maltose (0.02% w/v
as glucose). In general, though, because beer has the sugar maltose in it, it
is by far the most fattening of all alcoholic beverages. Most alcoholic
beverages when consumed with a meal help delay digestion and thereby
have a favorable effect on the glycaemic index of the meal. The maltose in
beer is digested more rapidly than any other food and causes large swings in
blood sugar and insulin levels. This is the origin of a beer belly. We do not get
wine bellies because wine does not contain maltose. Light beers with lower
carbohydrate content are better than regular beers.7
Table IV. Sugar content of a range of beers.
Beer
Lager
Light lager
Pale ale
All values in % (w/v) and derived from Thomas et al

Maltose
0.008
0.01
0.0003

Brewers wort (to make beer, brewers use water and barley to create a
sweetened liquid called the wort, which they flavor with hops, then ferment
with yeast) contains the sugars sucrose, fructose, glucose, maltose,
maltotriose, dextrin material, and a complex mixture of amino acids,
peptides, proteins, vitamins, ions, nucleic acids and other constituents.8
c) Beer contains barley

7 C.W. BAMFORTH: Beer, Carbohydrates and Diet. Journal of The Institute of

Brewing.
8 Sandra HdC, Eduardo MC, Jos RE: Structural Complexity on the Nitrogen Source
and Influence on Yeast Growth and Fermentation. J. Inst. Brew. 108(1):5461, 2002

Good brewing practices from barley to beer are important for the production
of a high quality beverage. Water is added to barley to trigger the
germination of the barley during the steeping step of the malting process.
Germinating barley can be held under anaerobic conditions for 24 hours or
more, until it becomes acidic due to the action of naturally present LAB.
Alternatively, malt can be sprayed with a suspension of Lb. delbrueckii and
then incubated at approximately 50C for a period of 2436 hours before
kilning17. A third method is that the kilned malt is steeped in water at 45
50C until the LAB in the malt have formed about 1% lactic acid. The malt is

carefully dried, thus concentrating the lactic acid to between 2 and 4%.9
Fig. 2c. Basic schematic representation of the brewing process. 10

Coronary Artery Diseases (CAD)

a) CAD is caused by atherosclerosis
Atherosclerosis begins as deposits of cholesterol and its esters, referred to as
fatty streaks, in the intima of large muscular arteries. In some persons and at
certain arterial sites, more lipid accumulates and is covered by a
fibromuscular cap to form a fibrous plaque. Further changes in fibrous
plaques render them vulnerable to rupture, an event that precipitates
occlusive thrombosis and clinically manifest disease (sudden cardiac death,
myocardial infarction, stroke, or peripheral arterial disease).
The extent of both fatty streaks and raised lesions (fibrous plaques and
other advanced lesions) in the right coronary artery and in the abdominal
aorta was associated positively with non-HDL cholesterol concentration,
hypertension, impaired glucose tolerance, and obesity and associated
negatively with HDL-cholesterol concentration.
9 Anne V, Tadhg OS, Douwe VS. Enhancing the Microbiological Stability of Malt and
Beer : A Review. J. Inst. Brew. 111(4), 355371, 2005

There has been little or no doubt for many years that the raised lesions
of atherosclerosis (a collective term for fibrous plaques and the associated
complications) determine the risk of clinically manifest coronary artery
disease (CAD), both for populations and for individuals. CAD events become
frequent in a population when the average extent of coronary artery raised
lesions in middle-aged persons approaches 30% of the coronary intimal
surface; individuals with CAD have on average 60% of the coronary intimal
surface involved with raised lesions. Recent studies by angiography,
ultrasonography, and histochemistry show that the qualities of raised lesions
also predict risk of an occlusive event.
The relation of fatty streaks to more advanced lesions is different in the
coronary arteries than in the aorta. Fatty streaks begin to appear in the
coronary arteries 510 y later than in the aorta. Comparisons of the
localization of lesions in the coronary arteries show a close correspondence
between the localization of fatty streaks in young persons and that of raised
lesions in older persons. In nonblack populations, the extent of coronary
artery fatty streaks in young persons predicts the extent of raised lesions in
older persons. However, although women have about the same extent of or
more coronary artery fatty streaks than do men, they have only half the
extent of raised lesions at older ages10

3. Conduct the Correlation among Factor

a) Alcohol - Atherosclerosis
Total homocysteine (tHcy) is recognized as a CVD risk factor. It is elevated in
patients with chronic alcoholism and falls following alcohol withdrawal;
therefore, alcohol may have a deleterious effect on health by raising tHcy
levels.11
It was shown that chronic alcohol intake among alcohol dependent patients
redounds to markedly elevated homocysteine plasma concentrations; the
data indicated that actively drinking alcoholics had twice the level of
10 Henry CMGJ, C Alex MM, Edward EH, Gray TM, Richard ET, Jack PS: Origin of
atherosclerosis in childhood and adolescence. The American Journal of Clinical
Nutrition. 2000;72(suppl):1307S15S

homocysteine in their plasma than did the healthy controls. In another study,
plasma homocysteine levels were found to be significantly correlated with
the extent of alcoholisation assessed with the blood-alcohol concentration
among alcoholic subjects at admission. The mean value of plasma
homocysteine levels fell after cessation of drinking from 33.6mol/l to
13.9mol/l on day 3 after admission. Several mechanisms contributing to the
hyperhomocysteinemia have been discussed. A direct inhibition of MS by
acetaldehyde, which is an alcohol breakdown product, might cause an
elevation of homocysteine levels. Homocysteine is metabolized via
remethylation and transsulphuration, for reactions, folate, vitamin B6 as well
as vitamin B12 are essential co-factors. Reduced availability of folate,
vitamin B6 and vitamin B12 cause an impairment of homocysteine
metabolism. Low folate intake, poor absorption, decreased hepatic uptake
and retention, increased urinary excretion of folate account for the folate
deficiency observed among alcohol dependent patients. Genetic factors
involved in homocysteine and folate metabolism also may contribute to the
association between elevated homocysteine plasma concentrations and
alcohol dependence. An excess of MTHFR 677T-allele found among alcohol
dependent patients compared to healthy control subjects potentially affects
homocysteine plasma levels.12
Elevated homocysteine levels (also called hyperhomocysteinemia) may
cause irritation of the blood vessels. Elevated levels of homocysteine show
an increased risk for (1) hardening of the arteries (atherosclerosis), which
could eventually result in a heart attack and/or stroke, and (2) blood clots in
the veins, referred to as venous thrombosis. An elevated homocysteine level
is associated with an increased risk for developing atherosclerosis, which can
in turn lead to coronary artery disease (CAD), heart attack, and stroke. The
magnitude of risk for CAD is not well defined. Generally, it seems that people
with an elevated homocysteine level may have about twice the risk of CAD
compared with those without a high homocysteine level. However, the risk is
dependent on the homocysteine level. For example, in one study,
researchers found that for every 10% elevation in homocysteine, there was
nearly the same rise in the risk of CAD. The risk may also be related to how
long someone has had an elevated homocysteine level.13

11 A. GIBSON, et al. Alcohol increases homocysteine and reduces B vitamin

concentration in healthy male volunteersa randomized, crossover intervention
study. Q J Med 2008; 101:881887
12 Ulrich C.L: Alterations in Homocysteine Metabolism Among Alcohol Dependent
Patients Clinical, Pathobiochemical and Genetic Aspects. Current Drug Abuse
Reviews, 2008, 1, 47-55

b) Maltose Atherosclerosis
The maltose in beer is digested more rapidly than any other food and causes
large swings in blood sugar and insulin levels.
Metabolic syndrome is strongly associated with endothelial dysfunction
and increased atherosclerosis risk. Insulin resistance and adaptive
hyperinsulinemia are thought to cause endothelial dysfunction and exert
mitogenic influences on vascular smooth muscle cells, in contrast to insulins
vasodilatory effect by promoting NO release under normal physiological
conditions.
Circulating adipokine levels are elevated in obese and insulin resistant
states in animals and humans, and intra-abdominal fat appears to produce
several of the adipokines in greater amounts than other fat depots.
A large number of adipokines also affect insulin action, blood sugar,
and fat metabolism and consequently insulin resistance, which ultimately
leads to Type 2 diabetes. Hence, they exert direct as well as indirect
influences on the process of atherosclerosis.
Furthermore, leptin increases platelet aggregation and arterial
thrombosis via a leptin receptor-dependent pathway, has a direct action on
macrophages by increasing the release of monocyte colony-stimulating
factor, promotes cholesterol accumulation in macrophages under high
glucose conditions, and stimulates angiogenesis. 14

13 Elizabeth A.V, Amy C.S, Caron P.M, Stephan M : Homocysteine and MTHFR
Mutations : Relation to Thrombosis and Coronary Artery Diseases. Journal of The
American Heart Association. Circulation 2005, 111:e289-e293
14 David C. W. Lau, et al. Adipokines: molecular links between obesity and
atherosclerosis. Am J Physiol Heart Circ Physiol 288:H2031-H2041, 2005. First
published 14 January 2005

Fig. 2. Effects of metabolic syndrome of insulin resistance on endothelial dysfunction. Insulin resistance
and adaptive hyperinsulinemia are thought to cause endothelial dysfunction by promoting endothelial
activation and a proatherogenic environment. The adipokines reinforce these detrimental effects. The
molecular links between obesity and atherosclerosis are explored through the effects of fat-derived
15
adipokines on endothelial function and vascular health.

c) Barley Atherosclerosis
Barley is the source of carbohydrates and is largely found in beer drink.
Barley is one of the main components in malting process. So it shows that
barley contains high carbohydrates.
TABLE C : TOTAL CARBOHYDRATE CONTENT OF BEVERAGES 15
Food
Carbohydrate (g) per serving
Beer
10 -20
Light and low carb beer
2.5 - 10
Based on the table above, it shows that beer have high contents of
carbohydrate. Consuming large amount of carbohydrates, will eventually
lead to obesity.
TNF-, an inflammatory cytokine released in greater quantities by
obese humans and patients with insulin resistance, not only initiates but also
propagates atherosclerotic lesion formation. TNF- activates the
transcription factor nuclear factor-B (NF-B), which accelerates
experimental atherogenesis, in part by inducing the expression of VCAM-1,
ICAM-1, MCP-1, and E-selectin in aortic endothelial and vascular smooth
muscle cells. TNF- reduces NO bioavailability in endothelial cells and
impairs endothelium-dependent vasodilatation, promoting endothelial
15 C.W. BAMFORTH: Beer, Carbohydrates and Diet. Journal of The Institute of
Brewing.

dysfunction. TNF- may also promote apoptosis in endothelial cells by

dephosphorylating protein kinase B, or Akt, and thereby contribute to
endothelial injury, an effect counteracted by insulin.16

4. Explore the Surrounding Factors

Metabolic syndrome has big influence on atherosclerosis
CAD risk can be calculated from risk factors and the presence of clinical signs
and biochemical abnormalities. The Framingham risk score is often used as
an initial evaluation parameter of CAD risk in individuals with countless risk
factors, including those with Metabolic Syndrome (MS).
The MS is a multiple risk factor for cardiovascular disease and is
characterized by increased waist circumference, raised triglycerides, reduced
HDL cholesterol, elevated blood pressure, and raised plasma glucose. From
these, reduced HDL-c and elevated blood pressure
are common components of both CAD risk and MS.
Some factors related to MS such as dyslipidemia, hyperglycemia,
hypertension, obesity and other risk factors like low levels of physical activity
and smoking have already been well established as CAD risk factors.
Diagnosis of Metabolic Syndrome was made according to the criteria of
NCEP-ATP III. The 5 components used were plasma levels of triglyceride, HDL16 AAFJE SIERKSMA, et al. Effect of Moderate Alcohol Consumption on Adiponectin,
Tumor Necrosis Factor-Alpha, and Insulin Sensitivity. DIABETES CARE, VOLUME 27,
NUMBER 1, JANUARY 2004

C and, fasting plasma glucose, systolic and diastolic blood pressure and WC
measurements. Metabolic syndrome was diagnosed when 3 or more of these
components were abnormal.
The association between MS and CAD risk found in this study was
similar the one observed in studies conducted in the United States and
Europe, where they found a 2 to 3 times greater probability for an increase in
CAD risk in individuals with MS. A positive correlation was observed of CAD
risk score and the number of MS components, that is, the greater the number
of MS components the higher the risk of developing CAD.
In this study, recommended intake of saturated fats and dietary fiber
are, together with greater muscle mass, inversely associated with CAD risk
score. On the other hand, the presence of MS and high plasma uric acid are
associated with CAD risk score.17
So, in our study we shall exclude maltose and barley as the component that
cause atherosclerosis, because it is not both maltose and barley that cause
atherosclerosis, but consumption of both maltose and barley cause
metabolic syndrome. Insulin resistance is caused by high intake of maltose
while obesity is caused by high intake of barley that eventually caused the
incidence of atherosclerosis formation.
So, to make our experiment more reliable and accurate, we just take
alcohol as the component in beer that causes CAD.

17 Mauro MT,et al. Metabolic syndrome & dietary components are associated with
coronary artery disease risk score in free-living adults:a cross-sectional study.
Diabetology & Metabolic Syndrome 2011, 3:7

THEORITICAL FRAMEWORK
18, 19,
20

Smoking

Hypertensio
1
4

Irritation of
blood vessel
High
amount
of
ALCOHOL

12
,
13

[6],
[7]

High beer
drinking
(>3
glass/day) [3]

Elevated
homocysteine
plasma
concentrations

High
amount
of

Coronary
Artery
Disease
(CAD)
[5]

Atherosclero
4

Venous
thrombosis

Circulating
adipokine level

Insulin
resistance

5
2

Diabetes Mellitus

10

High
amount of

Dependent &
Independent variable

Increased
source of
carbohydrate
The correct
experimental
pathway

Obese
Confoundin
g factor

Relationshi
p linkage

TNF- is
released in
greater

Dyslipidemi