1

1.

(coronary
heart disease)

: Association between caffeien

beverage and the risk factor for
Coronary heart disease of patient in
medicine clinic

Rajavithi

Hospital.
2.

2.1

(Oraphin Ubonnoi.MD)

: 0813785175
E-mail address:
:

Aubonnoi@gmail.com
80

2.2 /:

20

3.
q
q
q

(Basic research)
(Applied research)
(Experimental development)

4.

5. (keywords)
Coffee; Caffeine; Coronary heart disease;Acute
coronary syndrome
6. (Background)

(coronary heart disease)

( Acute coronary syndrome)

3-3.5%

1 5

1 100,000

..2549-2553
3

2 ..2549-2553

1

( Acute coronary syndrome)
1

CAD CAD

CHD first degree

relative < 55

Obesity (BMI 30

CHD first degree

kg/m )

relative < 65

( BP >=

>/= 45 ,

140/90 mmHg.)

>/= 55

, (caffeine)
Low HDL
cholesterol (</=60 mg/dL)
*

Hight LDL cholesterol

metabolic syndrome
3

( Acute coronary syndrome)

, (caffeine)
,

Metabolism of Caffeine

1 caffeine
metabolism cell

Metabolism of Caffeine

45 (
half-life) 3-5


3 %
7080% N 3-demethylation Paraxanthine 1,7
dimethylxanthine. CYP 1A2
95 %
xanthine
adenosine
receptors phosphodiesterase (phosphodiesterase

enzymes) sensitizer calcium channels

GAPA receptor
cytoplasmic Ca2+
(vascular smooth muscle cell)
VSMC cyclic adenosine monophosphate (cAMP)
(nitric oxide)

1. translocations of intracellular calcium,

2. increasing accumulation of cyclic nucleotides
3. blockade of receptors for adenosine

2 (Direct effect)

2 VSMC
Direct effect . voltagedependent Ca2+ channels

inositol triphosphate

(IP3) ( IP 3 Ca2+ ) Ca2+

independent
antiphosphodiesterase action.

3 ( Indirect effect )
3 Indirect effect VSMC
cytoplasmic Ca2+
nitric oxide synthase enzyme NO.
3 Indirect effect VSMC
cytoplasmic Ca2+
nitric oxide synthase enzyme NO.

10

3 Indirect effect VSMC

cytoplasmic Ca2+

nitric oxide synthase enzyme NO.

Adenosine Receptors. Adenosine receptor
Adenosine
chemoreceptor sympathetic
tone cathecolamines peripheral
vascular resistance and renin secretion.
300mg
systolic blood pressure 6 to 7.5mmHg.
diastolic blood pressure 2.6 to 4mmHg.

11

4 Adenosine

1.

2.
3. ( cholesterol)
4. (
Acute coronary syndrome or myocardial infraction )

(coronary heart disease)

12

(coronary heart
disease)
7.
7.1

(coronary heart disease)

7.2 : :
7.2.1

7.2.2

8.

13

( coronary heart disease)

9.

10.(Review of literature)
Coffee and Coronary Heart Disease
, Martin G. Myers, MD, FRCPC; Antoni

Basinski, MD, PhD, CCFP Arch Intern

14

Med. 1992;152(9):1767-1772. doi:10.1001/archinte.1992

prospective cohort 1966 August

1991
</= 1
/



1-4 /


1 / (odds ratio, 1.01; confidence
interval [0.93,1.11]).
4-6

6 / odds ratio 0. .01 (0.90,1.12)

and respectively 1.09 (97,1.22 )

Coffee and tea consumption and the
prevalence of coronary heart disease in men and women:
results from the Scottish Heart Health Study.
C A Brown, C Bolton-Smith, M Woodward, H TunstallPedoe.Journal of Epidemiology and
Community Health 1993; 47: 171-175.
10,359 40-59
9,740 ( = 4897, = 4843)

15

standard questions
prevalence

high coffee consumption

low coffee consumption

prevalence

high tea consumption

low tea consumption

sub

group analysis

cholesterol 2 %
(2% increase between 0 cups/day and 6
cups/day, p<005)

Does coffee drinking increase the

risk of coronary heart disease? Ichiro
Kawachi, Graham A Colditz, Catherine B Stone
Br HeartJ7 1994;72:269-275 meta analysis
review 8 case control studies 15 cohort studies

16

case control odds ratio (

5/) 1.63 ( 95% confidence

interval = 1.5-1.78)

cohort studies relative

risk ( 5 /) 1.5 ( 95% CI = 0.99

1.12)

cohort studies

case control rule out

subgroup

Coffee Consumption and Coronary

Heart Disease in Women A Ten-Year Follow-up
Walter C.Willett,MD, DrPH;Meir J,
Stampfer,MD,DrPH; E.Manson,MD,DrPH;Graham A
Colditz,MD, DrPH;Brenard A.Rosner,PhD;Frank E.
Speize,MD;Chaeles H. Hennekens,MD,DrPH
JAMA. 1996;275(6):458-462
85,470 34 59

17

CHD, stroke, or cancer.

6 / relative risk 0.95 ( 95% CI

= 0.73 1.26)

Coffee consumption and risk of

coronary heart disease Francesco Sofi ,
Andrea A. Conti , Anna Maria Gori , Maria Luisa Eliana
Luisi , Alessandro Casini ,Rosanna Abbate , Gian Franco
Gensini , Nutrition, Metabolism &
Cardiovascular Diseases (2007) 17, 209-223
meta analysis cases control 13
paper ( N= 37,234) cohort studies 10 paper ( N
=403,631 ) F/U 3 -14
case control studies

> 4 / odds ratio =
1.83 ( 95% CI = 1.49 2.24) ( P < 0.0001)

18

3-4/ odds ratio = 1.33 ( 95% CI =

1.04-1.71 ) ( P < 0.0001 )

2 /
odds ratio = 1.03
(95% CI = 0.87-1.21) (P= 0.45) cohort
studies

> 4 / relative
risk = 1.16 ( 95% CI = 0.95 1.41)(P = 0.14)

3-4 / relative risk = 1.05 (95% CI= 0.901.22)

( P = 0.57)
2
/ relative risk = 1.04
( 95% CI = 0.09-1.19 ) ( P = 0.6)

case control studies

Association of Coffee Drinking with

Total and Cause-Specific Mortality
Neal D. Freedman, Ph.D., Yikyung Park,
Sc.D., Christian C. Abnet, Ph.D., Albert R. Hollenbeck,
Ph.D., and Rashmi Sinha, Ph.D.N Engl

19

J Med 2012; 366:1891-1940

National Institutes of Health (NIH)AARP Diet and

Health Study 617,119
50 -71


566,401
1995-1996 F/U 4 -9

large prospective cohort study

10. (Reference)
1. Miners J. O.

and Birkett D. J, The use of caffeine as a

metabolic probe for human drug metabolizing

enzymes, General

Pharmacology, vol. 27, no. 2, 1996;pp. 245249.

2..Miners J. O and McKinnon R. A., CYP1A in Metabolic

Drug Interactions, Eds., Lippincott Williams &Wilkins, New York, NY,

USA, 2000; pp. 6173.

20

3.Daro Echeverri, Felix R.Montes,Mariana Cabrera,et.al.

Review Article Caffeines VascularMechanisms of Action ,

International Journal of Vascular Medicine,
30 June 2010;pp. 1-7.

4. Amer Suleman , Nasir Hameed Siddiqui ., Haemodynamic

and cardiovascular effects of caffeine, Pharmaceutical and Chemical
Development and Production, from:URL;
http://www.priory.com/pharmol/caffeine.htm.
5. ,,
from:URL;http://www.budmgt.com/tech/tech01/tonic-formula.html.
6.

.. ,

, from:URL;
http://www.pharmacy.cmu.ac.th/dic/newsletter/newpdf
7. Martin G. Myers, FRCPC; Antoni Basinski,: Coffee and

Coronary Heart Disease,. Med Arch Intern 1992;152(9);pp. 17671772.

8. Brown C A, Bolton-Smith C, Woodward M ,Coffee and tea

consumption and the prevalence of coronary heart disease in men
and women: results from the Scottish Heart Health Study,Journal of
Epidemiology and Community Health 1993; 47: pp. 171-175.
9.Ichiro Kawachi, Graham A Colditz, Catherine B Stone,Does
coffee drinking increase the risk of coronary heart disease? Results
from a meta-analysis, Br HeartJ7 1994;72:pp. 269-275.

21

10. Walter C. Willett; Meir J. Stampfer; JoAnn E.

Manson,et,al. Coffee Consumption and Coronary Heart Disease in
WomenA Ten-Year Follow-up, JAMA. 1996;275(6):pp. 458-462.

11. Francesco Sofi, Andrea A. Conti, Anna Maria Gori,et,al.

Coffee consumption and risk of coronary heart disease: A metaanalysis, Nutrition, Metabolism & Cardiovascular Diseases (2007)
17; pp. 209-223.
12. Neal D. Freedman., Yikyung Park., Christian C.
Abnet,et,al. Association of Coffee Drinking with Total and CauseSpecific Mortality,N Engl J Med 2012; pp. 1,891-1,904.
13. J Bosch Canadian , Hamilton General Hospital, L
Richardson, THE HOPE (HEART OUTCOMES PREVENTION
EVALUATION) STUDY A large, randomized trial of the ACE
inhibitor, ramipril, and Vitamin E n patients at high risk of
cardiovascular events
Investigators: March 27, 2000; pp. 1- 13.

11.
-

22

12. /

12.1 Case control study

Prospective ()
Retrospective (
)
Flow chat ()
case control retrospective study

2

(coronary heart disease)

23

12.2

(Inclusion criteria)
- 40 80 ( Association of
Coffee Drinking with Total and Cause-Specific Mortality; N
Engl J Med 2012 and Coffee and tea consumption and the
prevalence of coronary heart disease in men and women:

24

results from the Scottish Heart Health Study; Journal of

Epidemiology and Community Health 1993).

(Exclusion criteria)
-
(schizophrenia), mania
- Alzheimer,
Dementia
-
-
12.3 subjects
( Sample size)

2 (Lemeshow et al.,1990)**
( Association of Coffee Drinking with Total and CauseSpecific Mortality; N Engl J Med 2012)

25

n1 =
n = kn1
1 =

1 = OR( 2)/OR( 2)+(1- 2)

2

= 2
OR = Odds Ratio = 0.70 ( Association of
Coffee Drinking with Total and Cause-Specific Mortality; N Engl J
Med 2012)

2
p-value = 0.05

sample size
1 = =
0.644,
2
0.73

= =

26

= 2
= ( 1- 2)/2 = 0.687

1 (2 )
5

1.96
= 0.2

, Power =

N/group = 450

1-

= 0.8

, Z

= 0.84

: Total N = N1 + N2 = 900

N1= sample size

= 450
N2= sample size

= 450
13. (Operation definition)
13.1 (coronary heart disease)

1. myocardial
infraction (previous MI).
Documented multivessel coronary disease
(~50% stenosis in at least two major coronary
arteries) or positive stress testing.

27

2. angina (previous angina).

( 1)
3. multivessel CABG or multivessel
PTCA.
4. cardiac catheter
> 70 %
investigation coronary
angiogram sternosis coronary artery

(coronary heart disease)
13.2
1. (

1-2
%)
2.
3. ,M-100,M150

13.3
1.

: - 1 250 cc

28

- 1 180 cc
- 1 150 cc
2. : - 150 cc
- 1 500 cc
- 1 500 cc

250 cc
3. : - 1 150 cc
4. : - 1
18 cc
- 1 50 cc
- 1 190 cc
- 1 750 cc
- 1 380 cc
- 1 630 cc
- 1 340
cc
- 1 150 cc
- 1 45 cc
- 1 30 cc ,
1 60 cc

29

INSTANT COFFEE

WEAK

27MG PER CUP

MEDIU 48MG PER CUP

M
STRON 68MG PER CUP
G
NON-INSTANT

WEAK

53MG PER CUP

COFFEE
MEDIU 62MG PER CUP
M
STRON 71MG PER CUP
G
DECAFFEINATED

2MG PER CUP

30

COFFEE
TEA

46MG PER CUP

( 250

1 )

40 - 70

25 - 40

18

/1

- 12

50 .

- 15

50 .

10

50 .

10

50 .

M-150 10

50 .

10

50 .

31

13.4

Data analysis

- SPSS
(Statistical Package for the Social Sciences,
version 14, SPSS Inc, Chicago, Ill, USA)
-

(Descriptive statistic)

(Dermographic data)
#

# Odds ratio

- (Inferentiel statistic)
T- test p-value 0.05

chi-square test p-value
0.05
Multiple logestics regression

32

13.5

(Measurement)
13.5.1

3
1.
(Checklist)

2.
(Checklist)
(Open-ended)


(
)
3.


(Checklist)
(Open-ended) 1

33

13.5.2.2
(coronary heart disease)

14.

55 55 55 55 55 55 56 56
1

34

15.

16.
-



-

35

17.

18.

5,000

2,500

36

1,000

8,500

(Patient Information Sheet)

37

() .

..081-378-5175 .
E-mail

Aubonnoi@gmail.com

/.........

(coronary
heart disease)

38

...900 . (/ ) 1
- 15 2556

1. 13

4
, , , ,
2. 10-15

39

40

19/1

10400. 081-378-5175

24 /E-mail Aubonnoi@gmail.com

(


)

41

1.

2.

3.

4.

7.

8.

9.

10.

42

M
. (02)3548108-37 2803

43

(Informed
Consent
:

Form)

(coronary heart disease)
.

.........................

............................. .. ..................

44

....................................................
....................................................
(................................................)
(................................................)
.
.

45

......................................................
......................................................
(................................................)
(................................................)
.

1. ()
2.

3.

()

4.

./ ./

46

5.

6. (
)

0 10,000
20,001 30,000

> 40,000

10,001 20,000
30,001 40,000

47

1. _________

___________
2. (BODY MASS INDEX)
______________ (18.5 - 22.99)
****** 2
3.

_____________________

3.1

3 in 1()

48

..(
/)
3.2

..(
/)
1.3

49

M-150

M-100

..
( /)
1.4

..
.

1.5

50

..