Eur. J. Epidemiol. 0392-2990 November 1992, p. 776-782
EUROPEAN
Vol. 8, No. 6
JOURNAL OF
EPIDEMIOLOGY
THE INDEPENDENT EFFECT OF HABITUAL CIGARETTE AND COFFEE CONSUMPTION ON BLOOD PRESSURE A. SALVAGGIO .1, M. PERITI**, G. QUAGLIA***, D. MARZORATI** and M. TAVANELLI*** *Istituto di Igiene e Medicina Preventiva - Universitgt deg# Studi di Milano - Via F. Sforza, 35 20122 Milano - Italy. **Clinica Medica Generale - Universitd degli Studi di Milano - Ospedale "L. Sacco" - Milano, Italy. ***Centro Diagnostico Italiano - Milano, Italy.
Key words: Blood pressure - Coffee - Smoking The authors investigated the possible relation between habitual cigarette and coffee consumption and blood pressure (BP) levels in 7506 men and 2095 women. The study population were managers and employees examined in northern Italy between 1986-1988. In particular, the hypothesis of a substantial independence between smoking-BP and coffee-BP was tested. BP levels were corrected for age, body mass index, physical activity, and alcohol consumption by analysis of covariance. Significantly, smoking was inversely related to BP, both in men (SBP, P < 0.001, DBP, P < 0.001) and women (SBP, P = 0.001, DBP, P = 0.012). In particular, the BP of non-smoking men, SBP/DBP, was 131.0/83.5, whereas in male smokers up to and over 20 cigarette/day, BP was 128.1/ 82.0 and 128.1/82.1 respectively. Coffee consumption was related to BP levels in men (SBP, P < 0.001; DBP, P = 0.009), but not in women (SBP, P = 0.320; DBP, P = 0.982). BP in male subjects was 131.3/83.5 in non-drinkers, 130.7/83.3 in those drinking 1-3 cups/day, 128.4/82.6 and 127.2/81.8 in drinkers of 4-5 and over 5 cups/day, respectively. No significant interactions were demonstrated, thus the relationship between habitual smoking and coffee consumption with BP appears to agree with an additive model.
INTRODUCTION
Cigarette smoking has been demonstrated to have an acute hypertensive effect, and rises in blood pressure (BP) (systolic/diastolic) of 11/9 mmHg have been reported within 10 minutes after smoking (3, 17). Coffee (200 mg caffeine) increased BP about 10/7 mmHg between one and two hours after consumption (9). Experimental observations have also found that the combination of smoking and coffee had a larger and more sustained effect than either stimulus alone (10). Despite the hypertensive effect attributed to acute coffee consumption, Klatsky et al. (12), in 1977, i Corresponding author.
analyzed data on more than 83,000 men and women examined by the Multiphasic Health Checkup and observed lower BP levels in subjects drinking six or more cups of coffee per day. Further, Bertrand et al. (6) report data showing a lower than expected percentage of hypertensives in persons consuming over 4 cups of coffee daily. Observations on Italian men and women (16, 19) examined during a health screening programme, also indicated that an association exists between habitual coffee consumption and lower BP levels (in men), systolic and diastolic, even after allowing for age, weight, habitual alcohol and cigarette consumption. Regarding habitual cigarette smoking, an inverse relationship with BP levels has been shown in both studies, as well as that of Erikssen & Enger (8) in 1832
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Scandinavian men, Seltzer (20) in 849 healthy US male subjects and more general studies including only men (1, 2) or both sexes (7, 12). MATERIALS AND METHODS
The study consisted of 9601 subjects, examined from September 1986-June 1988 as part of a programme of preventive medicine agreed upon between various companies and the Centro Diagnostico Italiano. These subjects, aged 18-65 years, were managers (executives) and employees (clerks) of both sexes whose characteristics are summarized in Table 1. The programme concentrated on cardiovascular prevention and early cancer diagnosis. Seventy-four percent of the subjects covered by the programme and asked to participate were examined. Ninety-eight percent of the subjects examined were employeed in Lombardia.
TABLE 1. - Characteristics of the study subjects (means _+ SD or percentages). Men Number
Women
7506
2095
Age (years)
43.8 ___ 9.0
38.7 _+ 10.6
BMI (kg/m 2)
25.5 _+ 3.0
22.8 _+ 3.4
Smoking - cigarettes/day
Coffee - cups/day
Alcohol - g/day
Physical activity - none or irregular regular intensive
0 1-20 > 20
60.2% 25.8% 14.1%
64.9% 28.5% 6.5%
0 1-3 4-5 > 5
15.7% 54.4% 21.6% 8.3%
20.6% 58.4% 16.0% 5.0%
0 1-30 31-60 > 60
24.9% 46.6% 21.8% 6.7%
52.4% 41.9% 5.0% 0.7%
54.2% 44.7% 1.1%
66.1% 33.7% 0.2%
Examined subjects fasted for 8 hours and were asked not to smoke for 2 hours. The examination was performed between 8:30 (am) and 12:30. Twelve doctors were involved in performing the examinations. A monthly 'audit' was performed to minimize intra- and inter-observer variations. The medical and paramedical personnel examining the subjects were unaware of the aims of the study. A questionnaire was administered to all the subjects by a doctor during the physical examination. The questionnaire is actually a collection of 'bar codes' which are selected using an optical pen, so the data are directly computerized. In addition to the physical examination, the following measurements were taken: BP according to the World Health organization recommendations (14), some anthropometric indexes, an electrocardiogram, respiratory function tests and some laboratory tests. Body mass index (BMI), weight (kg)/[height (m)] 2, was used as a weight index; weight was measured without shoes and clothes (only a standard bathrobe). The smokers were requested to indicate their habitual cigarette consuption. They were classified as smoking up to 20 or over 20 cigarettes/day. According to habitual coffee consumption, subjects were classified as non-drinkers, or drinkers of 1-3, 4-5, or over 5 cups/day. Alcohol consumption, expressed as fractions of a liter for wine and beer and number of glasses for spirits (30-ml glasses for strong liquors, 50-ml glasses for others) was transformed into grams of ethanol/day using Mallor's nomogram (13). The participants were thus classified as non-drinkers or drinkers of up to 30, 31-60, over 60 g ethanol/day. The subjects were further classified according to physical activity: none or irregular, regular but noncompetitive, or intense (over 4 hours of intense training weekly). Analysis of covariance (ANCOVA) was used to assess the statistical significance of differences in mean BP levels among cigarette and coffee consumption categories, adjusting BP for alcohol consumption, physical activity, age and BMI (22) for each sex. We expressed the mathematical models for analysis of covariance as multiple regression models, in which, as confounding variables, continuos (age and BMI) and binary variables were introduced (3 binary variables for alcohol consumption: up to 30 g/ day, 31-60 g/day, and over 60 g/day; 2 binary variables for physical activity: regular and intensive). In addition, the existence of a linear or curvilinear trend was tested using 'linear' and 'quadratic' contrasts between BP means observed in different cigarette (linear contrast: -1, 0, 1; quadratic contrast: 1, -2, 1) and coffee (linear: - 3, -1, 1, 3; quadratic contrast: -1, 1, 1, -1,) consumption categories (22). A first order interaction term was introduced to assess the independence of the relations of coffee and smoking with BP. A p-value of 0.05 or less was considered significant.
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and cigarette consumption was not significant in either men (SBP, P = 0.650; DBP, P < 0.754) or women (SBP, P = 0.634; DBP, P = 0.699). The relationship between BP and the adjusting variables are also summarized in Table 3 and 4 (footnotes). The relationship between age and BMI with BP appears to be very strong. So, a non-perfect adhesion of these relationships to a linear model may interfere with the estimation of relationships of BP with other variables and possibly generate spurious relationships. Thus, to confirm our results on the relationship between coffee and cigarette consumption and BP, we
RESULTS
Tables 2-4 show BP values, adjusted (and nonadjusted) for age, BMI, alcohol consumption, and physical activity, of the subjects in the various cigarette and coffee consumption categories. Classification according to cigarette consumption was significant in men (ANCOVA, F-test: SBP, P < 0.001; DBP, P < 0.001) and women (SBP, P = 0.001; DBP, P = 0.012) whereas, classification according to coffee consumption was significant in men (SBP, P < 0.001; DBP, P < 0.009) but not in women (SBP, P = 0.320; DBP, P = 0.982). Interaction between coffee
TABLE 2. - Mean systolic and diastolic blood pressure in male and female subjects by cigarette and coffee consumption. Mean values are both adjusted and non-adjusted. Men
Women
SBP
DBP
SBP
DBP
Smoking no
mean SD n (percent ~)
131.1 15.0 4516
yes, _< 20 cigarettes/day mean SD n (percent t)
127.5 14.4 1935
yes, _> 20 cigarettes/day mean SD n. (percent ~)
128.6 14.9 1055
Coffee No mean SD n (percent t)
130.7 14.3 1177
yes, 1-3 cups/day mean SD n (percent ~)
130.4 15.2 4082
yes, 4-5 cups/day mean SD n (percent I")
128.6 14.6 1622
yes, > 5 cups/day mean SD n (percent I")
128.0 14.6 625
131.0" (60.2%)
128.1" (25.8%)
128.1" (14.0%)
131.3" (15.6%) 130.7" (54.3%) 128.4" (21.6%) 127.2" (8.3%)
83.7 9.4 4516
81.6 9.1 1935
82.4 9.5 1055
83.2 8.8 1177 83.3 9.6 4082 82.7 9.3 1622 82.3 9.2 625
83.5* (60.2%)
82.0* (25.8%)
82.1" (14.0°/0)
83.5* (15.6%) 83.3* (54.3%) 82.6* (21.6%) 81.8" (8.3%)
122.4 14.9 1360
118.9 13.6 598
117.3 15.2 137
121.4 15.1 431 121.3 14.7 1224 120.0 14.3 336 120.5 13.2 104
* mean values adjusted for age, BMI, alcohol consumption, and physical activity. I" total percent. 778
121.9" 64.9%)
119.7" (28.5%)
117.0" (6.5%)
122.2" (20.6%) 121.7" (58.4%) 120.2" (16.0%) 119.0" (5.0%)
78.1 9.3 1360
76.2 8.6 598
76.3 8.7 137
77.9 8.6 431 77.3 19.3 1224 77.2 9.2 336 78.2 8.3 104
77.8* (64.9%)
76.7* (28.5%)
76.1" (6.5%)
78.5* (20.6%) 77.5* (58.4%) 77.2* (16.0%) 77.4* (5.0%)
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Cigarette smoking and blood pressure
TABLE 3. - Mean systolic and diastolic blood pressure in male subjects by cigarette and coffee consumption. Coffee consumption, cups/day 0
1-3
4-5
> 5
SBP Non-smokers mean SD n (percent t)
131.1
131.9"
14.4 893
131.4
131.6"
15.2 (11.9%)
2653
130.6
130.0"
14.6 (35.3%)
739
129.7
128.4"
15.7 (9.8%)
231
(3.1%)
Smokers, < 20 cigarettes/day mean SD n (percent I")
129.7
130.1"
14.1 200
128.2
129.3"
14.9 (2.7%)
1037
126.0
126.7"
13.7 (13.8%)
523
125.0
125.3"
12.3 (7.0%)
175
(2.3%)
Smokers, > 20 cigarettes/day mean
129.3
SD
12.8
n (percent t)
84
129.1"
129.0
129.0"
15.0 (1.1%)
392
128.1
127.8"
15.4 (5.2%)
360
128.4
127.6"
14.6 (4.8%)
219
(2.9%)
DBP Non-smokers mean SD n (percent ~)
83.3
83.7*
9.0 893
83.7
83.8*
9.5 (11.9%)
2653
84.0
83.5*
9.1 (35.3%)
739
83.4
82.5*
9.8 (9.8%)
231
(3.1%)
Smokers, < 20 cigarettes/clay mean SD n (percent t)
82.8
83.0*
8.3 200
81.7
82.4*
9.5 (2.7%)
1037
81.5
81.9"
9.1 (13.8%)
523
80.6
80.7*
7.9 (7.0%)
175
(2.3%)
Smokers, > 20 cigarettes/day mean SD n (percent ?)
82.8
82.8*
8.2 84
82.7
82.7*
9.7 (1.1%)
392
81.9
81.8"
9.6 (5.2%)
360
82.5
82.0*
9.3 (4.8%)
219
(2.9%)
* mean values adjusted for age (regression coeffficient __+SE, 0.32 _ 0.2 mmHg/year, P < 0.0001), BMI (1.27 _+ 0.06 mmHg/kg/m 2, P < 0.0001), consumption of up to 30 g ethanol/day (0.06 _ 0.43 mmHg, P = 0.8835), 31-60 (0.81 + 0.51 mmHg, P = 0.1094) and over 60 g ethanol/day (2.38 + 0.76 mmHg, P = 0.0016), and physical activity (regular, -0.44 __-0.35 mmHg, P = 0.2094; intensive -0.81 + 1.16 mmHg, P = 0.6151). I" total percent
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TABLE 4. - Mean systolic and diastolic blood pressure in female subjects by cigarette and coffee consumption. Coffee consumption, cups/day 0
1-3
4-5
> 5
SBP Non-smokers mean SD n (percent I")
121.9
122.9"
15.8 347
122.6
122.4"
14.6 (16.6%)
794
122.6
121.7"
15.2 (37.9%)
168
122.3
119.2"
12.6 (8.0%)
51
(2.4%)
119.4"
121.4
121.5"
Smokers, _< 20 cigarettes/day mean
120.4
SD
12.4
n (percent ?)
67
120.5"
118.6
120.2"
13.9 (3.2%)
374
118.2 13.2
(17.9%)
123
14.3 (5.9%)
34
(1.6%)
116.7"
113.8
114.0"
Smokers, > 20 cigarettes/day mean
116.2
SD
10.7
n (percent I")
17
115.9"
120.2
119.4"
19.0 (0.8%)
56
115.5 12.1
(2.7%)
45
10.8 (2.1%)
19
(0.9%)
DBP Non-smokers mean SD n (percent t)
78.2
78.8*
8.8 347
77.7
77.6*
9.4 (16.6%)
794
78.7
78.1"
10.0 (37.9%)
168
80.1
78.3*
8.3 (8.0%)
51
(2.4%)
Smokers, < 20 cigarettes/day mean SD n (percent -~)
77.0
77.2*
7.4 67
76.2
77.1"
8.9 (3.2%)
374
75.5
76.2*
8.4 (17.9%)
123
77.2
77.2*
8.2 (5.9%)
34
(1.6%)
Smokers, > 20 cigarettes/day mean SD n (percent I-)
75.3
75.3*
9.8 17
77.3
76.8*
9.6 (0.8%)
56
75.9
76.6*
7.6 (2.7%)
45
75.0
75.0*
7.3 (2.1%)
19
(0.9%)
* mean values adjusted for age (regression coefficient + SE, 0.45 _+ 0.03 mmHg/year, P < 0.0001), BMI (1.23 _ 0.09 m m H g / k g / m 2, P < 0.0001), consumption of up to 30 g ethanol/day (-0.48 + 0.61 m m H g P = 0.4350), 31-60 (-2.25 ___1.35 mmHg, P = 0.0948) and over 60 g ethanol/day (-0.31 + 3,37 mmHg, P = 0.9256), and physical activity (regular, -1.31 + 0.63 mmHg, P = 0.0382; intensive 3.96 _+ 5.59 mmHg, P = 0.4786). t total percent.
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re-analyzed these adjusting BP levels for age and BMI introduced as linear, quadratic and interactive terms (alcohol consumption and physical activity). Even so, no substantial variations were found in the coffee-BP and cigarette-BP relationships. In men, coffee consumption and smoking were reconfirmed as important explicative variables (SBP: coffee consumption, P < 0.001; smoking, P < 0.001; DBP: coffee consumption, P = 0.030; smoking, P < 0.001). In women, as in the previous analyses, only smoking was confirmed as an important variable (SBP: coffee consumption, P = 0.834; smoking, P < 0.001; DBP: coffee consumption, P = 0.487; smoking, P = 0.038). The analysis of linear and quadratic contrasts among BP means observed in different coffee consumption categories suggests a substantially linear, inverse relationship between BP and habitual coffee consumption in men but not women (men, SBP/ DBP: linear, P < 0.0001/P = 0.0032, quadratic, P = 0.1233/P = 0.2505; women: linear, P = 0.2043/ P = 0.5431, quadratic, P = 0.4639/P = 0.1948). However, between BP and smoking the relationship appear to be curvilinear, with lower BP levels in smokers, but similar levels in male smokers varying by number of cigarettes (men, SBP/DBP: linear, P = 0.0001/P = 0.0006, quadratic, P = 0.0010/P = 0.0014; women: linear, P = 0.0002/P = 0.7105, quadratic, P = 0.0389/P -- 0.7178). Interaction between coffee and cigarette consumption was not significant in either men or women (men, SBP/DBP: P = 0.6744/P = 0.7961; women: P = 0.6682/P = 0.9020. DISCUSSION
In this study a significant relationship was found between habitual cigarette consumption and BP levels, with lower BP levels in smokers than nonsmokers (Tables 2-4). Furthermore, contrary to shortterm observations, habitual coffee drinkers presented lower BP levels than non-drinkers and, in men, increasingly lower mean BP levels were observed with increases in the amount of coffee habitually drank (Tables 2-4): this relationship was more evident for systolic blood pressure. When simple linear and quadratic contrasts were introduced to analyze coffee consumption and smoking, a significant 'linear' inverse relationship was found between coffee consumption and BP, both systolic and diastolic. A significant, non-linear relationship was found between cigarette smoking and systolic and diastolic BP, with lower levels in 'smokers' than non-smokers, and small differences between smokers of _< 20 cigarette/day and over 20 cigarette/ day. Studies using serum cotinine concentration, the major metabolite of nicotine that reflects daily intake of nicotine, indicate a linear inverse relationship between cotinine levels and BP (5). However, no BP differences among smokers based on level of cigarette consumption grouping were observed (5). Thus, the 781
non-linear, inverse relationship between cigarette smoking and BP observed by us might to be an expression of a divergence between actual tobacco smoke exposure and its assessment based on level of habitual cigarette consumption. It is possible that smokers titrate their intake of nicotine, taking more nicotine per cigarette when smoking fewer compared to a greater number of cigarettes. Naturally, it is not possible to infer causal relations from cross-sectional results such as those presented here. However, our observations suggest a possible dose dependence of the relationship between BP and both cigarette and coffee consumption. Our observations relate the medium/long-term effects of habitual cigarette and coffee consumption to BP, evaluated as 'basal' BP. BP levels during the day have to be considered before inferences on the eventual consequences of smoking or coffee consumption, resulting from prolonged but reversible variations of BP levels, can be made. In fact, we cannot extrapolate from BP values recorded in abstinent smokers to BP during the average day. Smoking individual cigarettes may only increase BP for 30-60 minutes, but daily cigarette consumption may to be enough to significantly raise average BP levels during the day. Thus, our observation of normal BP, or even lower than normal, in smokers suggests an integrity of hemostatic mechanisms to counter (short-term) cigarette-induced blood pressure elevation. It may be a temporary 'reset' of BP since 'basal' blood pressure tends to rise when smokers give up the habit (9). The same is also theoretically valid for coffe consumers, even if a recent study found that caffeine increased BP only in nontolerant subjects but had little effect on BP in regular coffee drinkers (21). Relationships that involve coffee consumption in Italian subjects are particularly interesting given that the typical Italian brewing method is vaporisation under pressure, the so-called 'espresso' (15), a method different from those used in other countries, such as filtering or boiling. Water (the extracting liquid) is brought to a temperature slightly higher than the boiling point and is passed through a bed of coffee placed on a filter. Thus, the water temperature is higher than in both boiling and filtering under gravity methods (and its variants, notably filtration under pressure and filtration with recirculation, as used in 'percolators') (4). However, extraction time, about 100 seconds, is brief. Finally, the 'consumption of cigarettes' and the 'consumption of coffee' appear heavily associated (X2test for independence of the subjects' classification by smoking and coffee consumption: men, Table 3, P < 0.0001; women, Table 4, P < 0.0001). Experimental observations showed a larger and sustained 'hypertensive' effect of contemporary coffee and cigarette consumption than either stimulus alone (10). However, caffeine would be able to inhibit the hypertensive activity of nicotine 'in acuto' (24), and an accelerated catabolism of caffeine is reported in smokers (23).
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Fur. J. Epidemiot.
In our observations, all interactive terms, relative to an eventual interaction between coffee and cigarette consumption with respect to BP levels, were not significant (Table 6). Thus, smoking and coffee consumption appear to be associated with BP levels according to an additive model. It is possible that eventual chronic effects of cigarette and coffee are produced independently, as well as eliminate a possible interactive effect. Our observations have confirmed, in Italian subjects, the inverse relationships between cigarette and coffee consumption and BP. Some important details were analyzed in depth. Thus, a substantial independence between chronic effects o f coffee consumption and smoking on BP was demonstrated. Moreover, unlike some observations (11, 18), even if weight (BMI) is taken into account in a complex fashion (relating it to BP by linear and quadratic terms and considering eventual interactions with age), we found that the relationship between cigarette and coffee consumption and BP do not disappear.
Acknowledgements We acknowledge with thanks the most constructive comments and suggestions of the anonymous reviewers.
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9. Freestone S. and Ramsay L.E. (1982): Pressor effect of coffee and cigarette smoking in hypertensive patients - Clin. Sci. 63 (suppl. 8): 403s-5s. 10. Freestone S. and Ramsay L.E. (1982): Effect of coffee and cigarette smoking on the blood pressure of untreated and diuretic-treated hypertensive patients Am. J. Med. 73: 348-53.
11. Karvonen M., Orma E., Keys A., Fidanza F. and Brozek J. (1959): Cigarette smoking, serum-cholesterol, blood-pressure and body fatness. Observations in Finland - Lancet i: 492-4. 12. Klatsky A.L., Freedman G.D., Sieglaud A.B. and Gkrard M.J. (1977): Alcohol consumption and blood pressure. Kaiser Permanente Multiphasic Health examination data - N. Engl. J. Med. 296: 1194-200. 13. Mallor C.S. (1970): Nomogram for calculating mass of alcohol in different beverages - (letter) Br. Med. J. 3: 703. 14. Participants at the Fourth Mild Hypertension Conference (1986): 1986 Guidelines for treatment of mild hypertension: memorandum from a W H O / I S H Meeting - J. Hypertension 4: 383-6. 15. Piaet G. (1987): Home catering brewing of coffee. In: 'Coffee' Vol. 2 - Technology, Edited by R.J. Clarke and R. MacRae, Elservier Applied Science, London, pp 221-52. 16. Periti M., Salvaggio A., Quaglia G. and Di Marzio L. (1987): Coffee consumption and blood pressure: an Italian study - Clin. Sci. 72: 443-7. 17. Rabinowitz B.D., Thorp K., Huber G.L. and Abelmann W.H. (1979): Acute hemodynamic effects of cigarette smoking in man assessed by systolic time intervals and echocardiography - Circulation 60: 752-60. 18. Reid D.D., Holland W.W., Humetfelt S. and Rose G. (1966): A cardiovascular survey of British postal workers - Lancet i: 614-8. 19. Salvaggio A., Periti M., Miano L. and Zambelli C. (1990): Association between habitual coffee consumption and blood pressure - J. Hypertension 8: 585-590. 20. Seltzer C.C (1974): Effect of smoking on blood pressure - Am. Heart J. 87: 558-64. 21. Sharp D.S. and Benowitz N.L. (1990): Pharmacoepidemiology of the effect of caffeine on blood pressure - Clin. Pharm. Ther. 47: 57-60. 22. Snedecor G.W. and Cochran W.G. (1980): Statistical methods. 7th edition - Iowa State University Press, Ames, pp 365-92, 404-7.
7. Chiqui M.I-I., Wallace R.B., Mishkel M., BarretConnor E. and Heiss G. (1981): Alcohol consumption and blood pressure. The Lipid Research Clinics Prevalence Study - Hypertension 3: 557-65.
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EUROPEAN
Vol. 8, No. 6
JOURNAL OF
EPIDEMIOLOGY
THE INDEPENDENT EFFECT OF HABITUAL CIGARETTE AND COFFEE CONSUMPTION ON BLOOD PRESSURE A. SALVAGGIO .1, M. PERITI**, G. QUAGLIA***, D. MARZORATI** and M. TAVANELLI*** *Istituto di Igiene e Medicina Preventiva - Universitgt deg# Studi di Milano - Via F. Sforza, 35 20122 Milano - Italy. **Clinica Medica Generale - Universitd degli Studi di Milano - Ospedale "L. Sacco" - Milano, Italy. ***Centro Diagnostico Italiano - Milano, Italy.
Key words: Blood pressure - Coffee - Smoking The authors investigated the possible relation between habitual cigarette and coffee consumption and blood pressure (BP) levels in 7506 men and 2095 women. The study population were managers and employees examined in northern Italy between 1986-1988. In particular, the hypothesis of a substantial independence between smoking-BP and coffee-BP was tested. BP levels were corrected for age, body mass index, physical activity, and alcohol consumption by analysis of covariance. Significantly, smoking was inversely related to BP, both in men (SBP, P < 0.001, DBP, P < 0.001) and women (SBP, P = 0.001, DBP, P = 0.012). In particular, the BP of non-smoking men, SBP/DBP, was 131.0/83.5, whereas in male smokers up to and over 20 cigarette/day, BP was 128.1/ 82.0 and 128.1/82.1 respectively. Coffee consumption was related to BP levels in men (SBP, P < 0.001; DBP, P = 0.009), but not in women (SBP, P = 0.320; DBP, P = 0.982). BP in male subjects was 131.3/83.5 in non-drinkers, 130.7/83.3 in those drinking 1-3 cups/day, 128.4/82.6 and 127.2/81.8 in drinkers of 4-5 and over 5 cups/day, respectively. No significant interactions were demonstrated, thus the relationship between habitual smoking and coffee consumption with BP appears to agree with an additive model.
INTRODUCTION
Cigarette smoking has been demonstrated to have an acute hypertensive effect, and rises in blood pressure (BP) (systolic/diastolic) of 11/9 mmHg have been reported within 10 minutes after smoking (3, 17). Coffee (200 mg caffeine) increased BP about 10/7 mmHg between one and two hours after consumption (9). Experimental observations have also found that the combination of smoking and coffee had a larger and more sustained effect than either stimulus alone (10). Despite the hypertensive effect attributed to acute coffee consumption, Klatsky et al. (12), in 1977, i Corresponding author.
analyzed data on more than 83,000 men and women examined by the Multiphasic Health Checkup and observed lower BP levels in subjects drinking six or more cups of coffee per day. Further, Bertrand et al. (6) report data showing a lower than expected percentage of hypertensives in persons consuming over 4 cups of coffee daily. Observations on Italian men and women (16, 19) examined during a health screening programme, also indicated that an association exists between habitual coffee consumption and lower BP levels (in men), systolic and diastolic, even after allowing for age, weight, habitual alcohol and cigarette consumption. Regarding habitual cigarette smoking, an inverse relationship with BP levels has been shown in both studies, as well as that of Erikssen & Enger (8) in 1832
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Scandinavian men, Seltzer (20) in 849 healthy US male subjects and more general studies including only men (1, 2) or both sexes (7, 12). MATERIALS AND METHODS
The study consisted of 9601 subjects, examined from September 1986-June 1988 as part of a programme of preventive medicine agreed upon between various companies and the Centro Diagnostico Italiano. These subjects, aged 18-65 years, were managers (executives) and employees (clerks) of both sexes whose characteristics are summarized in Table 1. The programme concentrated on cardiovascular prevention and early cancer diagnosis. Seventy-four percent of the subjects covered by the programme and asked to participate were examined. Ninety-eight percent of the subjects examined were employeed in Lombardia.
TABLE 1. - Characteristics of the study subjects (means _+ SD or percentages). Men Number
Women
7506
2095
Age (years)
43.8 ___ 9.0
38.7 _+ 10.6
BMI (kg/m 2)
25.5 _+ 3.0
22.8 _+ 3.4
Smoking - cigarettes/day
Coffee - cups/day
Alcohol - g/day
Physical activity - none or irregular regular intensive
0 1-20 > 20
60.2% 25.8% 14.1%
64.9% 28.5% 6.5%
0 1-3 4-5 > 5
15.7% 54.4% 21.6% 8.3%
20.6% 58.4% 16.0% 5.0%
0 1-30 31-60 > 60
24.9% 46.6% 21.8% 6.7%
52.4% 41.9% 5.0% 0.7%
54.2% 44.7% 1.1%
66.1% 33.7% 0.2%
Examined subjects fasted for 8 hours and were asked not to smoke for 2 hours. The examination was performed between 8:30 (am) and 12:30. Twelve doctors were involved in performing the examinations. A monthly 'audit' was performed to minimize intra- and inter-observer variations. The medical and paramedical personnel examining the subjects were unaware of the aims of the study. A questionnaire was administered to all the subjects by a doctor during the physical examination. The questionnaire is actually a collection of 'bar codes' which are selected using an optical pen, so the data are directly computerized. In addition to the physical examination, the following measurements were taken: BP according to the World Health organization recommendations (14), some anthropometric indexes, an electrocardiogram, respiratory function tests and some laboratory tests. Body mass index (BMI), weight (kg)/[height (m)] 2, was used as a weight index; weight was measured without shoes and clothes (only a standard bathrobe). The smokers were requested to indicate their habitual cigarette consuption. They were classified as smoking up to 20 or over 20 cigarettes/day. According to habitual coffee consumption, subjects were classified as non-drinkers, or drinkers of 1-3, 4-5, or over 5 cups/day. Alcohol consumption, expressed as fractions of a liter for wine and beer and number of glasses for spirits (30-ml glasses for strong liquors, 50-ml glasses for others) was transformed into grams of ethanol/day using Mallor's nomogram (13). The participants were thus classified as non-drinkers or drinkers of up to 30, 31-60, over 60 g ethanol/day. The subjects were further classified according to physical activity: none or irregular, regular but noncompetitive, or intense (over 4 hours of intense training weekly). Analysis of covariance (ANCOVA) was used to assess the statistical significance of differences in mean BP levels among cigarette and coffee consumption categories, adjusting BP for alcohol consumption, physical activity, age and BMI (22) for each sex. We expressed the mathematical models for analysis of covariance as multiple regression models, in which, as confounding variables, continuos (age and BMI) and binary variables were introduced (3 binary variables for alcohol consumption: up to 30 g/ day, 31-60 g/day, and over 60 g/day; 2 binary variables for physical activity: regular and intensive). In addition, the existence of a linear or curvilinear trend was tested using 'linear' and 'quadratic' contrasts between BP means observed in different cigarette (linear contrast: -1, 0, 1; quadratic contrast: 1, -2, 1) and coffee (linear: - 3, -1, 1, 3; quadratic contrast: -1, 1, 1, -1,) consumption categories (22). A first order interaction term was introduced to assess the independence of the relations of coffee and smoking with BP. A p-value of 0.05 or less was considered significant.
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and cigarette consumption was not significant in either men (SBP, P = 0.650; DBP, P < 0.754) or women (SBP, P = 0.634; DBP, P = 0.699). The relationship between BP and the adjusting variables are also summarized in Table 3 and 4 (footnotes). The relationship between age and BMI with BP appears to be very strong. So, a non-perfect adhesion of these relationships to a linear model may interfere with the estimation of relationships of BP with other variables and possibly generate spurious relationships. Thus, to confirm our results on the relationship between coffee and cigarette consumption and BP, we
RESULTS
Tables 2-4 show BP values, adjusted (and nonadjusted) for age, BMI, alcohol consumption, and physical activity, of the subjects in the various cigarette and coffee consumption categories. Classification according to cigarette consumption was significant in men (ANCOVA, F-test: SBP, P < 0.001; DBP, P < 0.001) and women (SBP, P = 0.001; DBP, P = 0.012) whereas, classification according to coffee consumption was significant in men (SBP, P < 0.001; DBP, P < 0.009) but not in women (SBP, P = 0.320; DBP, P = 0.982). Interaction between coffee
TABLE 2. - Mean systolic and diastolic blood pressure in male and female subjects by cigarette and coffee consumption. Mean values are both adjusted and non-adjusted. Men
Women
SBP
DBP
SBP
DBP
Smoking no
mean SD n (percent ~)
131.1 15.0 4516
yes, _< 20 cigarettes/day mean SD n (percent t)
127.5 14.4 1935
yes, _> 20 cigarettes/day mean SD n. (percent ~)
128.6 14.9 1055
Coffee No mean SD n (percent t)
130.7 14.3 1177
yes, 1-3 cups/day mean SD n (percent ~)
130.4 15.2 4082
yes, 4-5 cups/day mean SD n (percent I")
128.6 14.6 1622
yes, > 5 cups/day mean SD n (percent I")
128.0 14.6 625
131.0" (60.2%)
128.1" (25.8%)
128.1" (14.0%)
131.3" (15.6%) 130.7" (54.3%) 128.4" (21.6%) 127.2" (8.3%)
83.7 9.4 4516
81.6 9.1 1935
82.4 9.5 1055
83.2 8.8 1177 83.3 9.6 4082 82.7 9.3 1622 82.3 9.2 625
83.5* (60.2%)
82.0* (25.8%)
82.1" (14.0°/0)
83.5* (15.6%) 83.3* (54.3%) 82.6* (21.6%) 81.8" (8.3%)
122.4 14.9 1360
118.9 13.6 598
117.3 15.2 137
121.4 15.1 431 121.3 14.7 1224 120.0 14.3 336 120.5 13.2 104
* mean values adjusted for age, BMI, alcohol consumption, and physical activity. I" total percent. 778
121.9" 64.9%)
119.7" (28.5%)
117.0" (6.5%)
122.2" (20.6%) 121.7" (58.4%) 120.2" (16.0%) 119.0" (5.0%)
78.1 9.3 1360
76.2 8.6 598
76.3 8.7 137
77.9 8.6 431 77.3 19.3 1224 77.2 9.2 336 78.2 8.3 104
77.8* (64.9%)
76.7* (28.5%)
76.1" (6.5%)
78.5* (20.6%) 77.5* (58.4%) 77.2* (16.0%) 77.4* (5.0%)
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Cigarette smoking and blood pressure
TABLE 3. - Mean systolic and diastolic blood pressure in male subjects by cigarette and coffee consumption. Coffee consumption, cups/day 0
1-3
4-5
> 5
SBP Non-smokers mean SD n (percent t)
131.1
131.9"
14.4 893
131.4
131.6"
15.2 (11.9%)
2653
130.6
130.0"
14.6 (35.3%)
739
129.7
128.4"
15.7 (9.8%)
231
(3.1%)
Smokers, < 20 cigarettes/day mean SD n (percent I")
129.7
130.1"
14.1 200
128.2
129.3"
14.9 (2.7%)
1037
126.0
126.7"
13.7 (13.8%)
523
125.0
125.3"
12.3 (7.0%)
175
(2.3%)
Smokers, > 20 cigarettes/day mean
129.3
SD
12.8
n (percent t)
84
129.1"
129.0
129.0"
15.0 (1.1%)
392
128.1
127.8"
15.4 (5.2%)
360
128.4
127.6"
14.6 (4.8%)
219
(2.9%)
DBP Non-smokers mean SD n (percent ~)
83.3
83.7*
9.0 893
83.7
83.8*
9.5 (11.9%)
2653
84.0
83.5*
9.1 (35.3%)
739
83.4
82.5*
9.8 (9.8%)
231
(3.1%)
Smokers, < 20 cigarettes/clay mean SD n (percent t)
82.8
83.0*
8.3 200
81.7
82.4*
9.5 (2.7%)
1037
81.5
81.9"
9.1 (13.8%)
523
80.6
80.7*
7.9 (7.0%)
175
(2.3%)
Smokers, > 20 cigarettes/day mean SD n (percent ?)
82.8
82.8*
8.2 84
82.7
82.7*
9.7 (1.1%)
392
81.9
81.8"
9.6 (5.2%)
360
82.5
82.0*
9.3 (4.8%)
219
(2.9%)
* mean values adjusted for age (regression coeffficient __+SE, 0.32 _ 0.2 mmHg/year, P < 0.0001), BMI (1.27 _+ 0.06 mmHg/kg/m 2, P < 0.0001), consumption of up to 30 g ethanol/day (0.06 _ 0.43 mmHg, P = 0.8835), 31-60 (0.81 + 0.51 mmHg, P = 0.1094) and over 60 g ethanol/day (2.38 + 0.76 mmHg, P = 0.0016), and physical activity (regular, -0.44 __-0.35 mmHg, P = 0.2094; intensive -0.81 + 1.16 mmHg, P = 0.6151). I" total percent
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TABLE 4. - Mean systolic and diastolic blood pressure in female subjects by cigarette and coffee consumption. Coffee consumption, cups/day 0
1-3
4-5
> 5
SBP Non-smokers mean SD n (percent I")
121.9
122.9"
15.8 347
122.6
122.4"
14.6 (16.6%)
794
122.6
121.7"
15.2 (37.9%)
168
122.3
119.2"
12.6 (8.0%)
51
(2.4%)
119.4"
121.4
121.5"
Smokers, _< 20 cigarettes/day mean
120.4
SD
12.4
n (percent ?)
67
120.5"
118.6
120.2"
13.9 (3.2%)
374
118.2 13.2
(17.9%)
123
14.3 (5.9%)
34
(1.6%)
116.7"
113.8
114.0"
Smokers, > 20 cigarettes/day mean
116.2
SD
10.7
n (percent I")
17
115.9"
120.2
119.4"
19.0 (0.8%)
56
115.5 12.1
(2.7%)
45
10.8 (2.1%)
19
(0.9%)
DBP Non-smokers mean SD n (percent t)
78.2
78.8*
8.8 347
77.7
77.6*
9.4 (16.6%)
794
78.7
78.1"
10.0 (37.9%)
168
80.1
78.3*
8.3 (8.0%)
51
(2.4%)
Smokers, < 20 cigarettes/day mean SD n (percent -~)
77.0
77.2*
7.4 67
76.2
77.1"
8.9 (3.2%)
374
75.5
76.2*
8.4 (17.9%)
123
77.2
77.2*
8.2 (5.9%)
34
(1.6%)
Smokers, > 20 cigarettes/day mean SD n (percent I-)
75.3
75.3*
9.8 17
77.3
76.8*
9.6 (0.8%)
56
75.9
76.6*
7.6 (2.7%)
45
75.0
75.0*
7.3 (2.1%)
19
(0.9%)
* mean values adjusted for age (regression coefficient + SE, 0.45 _+ 0.03 mmHg/year, P < 0.0001), BMI (1.23 _ 0.09 m m H g / k g / m 2, P < 0.0001), consumption of up to 30 g ethanol/day (-0.48 + 0.61 m m H g P = 0.4350), 31-60 (-2.25 ___1.35 mmHg, P = 0.0948) and over 60 g ethanol/day (-0.31 + 3,37 mmHg, P = 0.9256), and physical activity (regular, -1.31 + 0.63 mmHg, P = 0.0382; intensive 3.96 _+ 5.59 mmHg, P = 0.4786). t total percent.
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re-analyzed these adjusting BP levels for age and BMI introduced as linear, quadratic and interactive terms (alcohol consumption and physical activity). Even so, no substantial variations were found in the coffee-BP and cigarette-BP relationships. In men, coffee consumption and smoking were reconfirmed as important explicative variables (SBP: coffee consumption, P < 0.001; smoking, P < 0.001; DBP: coffee consumption, P = 0.030; smoking, P < 0.001). In women, as in the previous analyses, only smoking was confirmed as an important variable (SBP: coffee consumption, P = 0.834; smoking, P < 0.001; DBP: coffee consumption, P = 0.487; smoking, P = 0.038). The analysis of linear and quadratic contrasts among BP means observed in different coffee consumption categories suggests a substantially linear, inverse relationship between BP and habitual coffee consumption in men but not women (men, SBP/ DBP: linear, P < 0.0001/P = 0.0032, quadratic, P = 0.1233/P = 0.2505; women: linear, P = 0.2043/ P = 0.5431, quadratic, P = 0.4639/P = 0.1948). However, between BP and smoking the relationship appear to be curvilinear, with lower BP levels in smokers, but similar levels in male smokers varying by number of cigarettes (men, SBP/DBP: linear, P = 0.0001/P = 0.0006, quadratic, P = 0.0010/P = 0.0014; women: linear, P = 0.0002/P = 0.7105, quadratic, P = 0.0389/P -- 0.7178). Interaction between coffee and cigarette consumption was not significant in either men or women (men, SBP/DBP: P = 0.6744/P = 0.7961; women: P = 0.6682/P = 0.9020. DISCUSSION
In this study a significant relationship was found between habitual cigarette consumption and BP levels, with lower BP levels in smokers than nonsmokers (Tables 2-4). Furthermore, contrary to shortterm observations, habitual coffee drinkers presented lower BP levels than non-drinkers and, in men, increasingly lower mean BP levels were observed with increases in the amount of coffee habitually drank (Tables 2-4): this relationship was more evident for systolic blood pressure. When simple linear and quadratic contrasts were introduced to analyze coffee consumption and smoking, a significant 'linear' inverse relationship was found between coffee consumption and BP, both systolic and diastolic. A significant, non-linear relationship was found between cigarette smoking and systolic and diastolic BP, with lower levels in 'smokers' than non-smokers, and small differences between smokers of _< 20 cigarette/day and over 20 cigarette/ day. Studies using serum cotinine concentration, the major metabolite of nicotine that reflects daily intake of nicotine, indicate a linear inverse relationship between cotinine levels and BP (5). However, no BP differences among smokers based on level of cigarette consumption grouping were observed (5). Thus, the 781
non-linear, inverse relationship between cigarette smoking and BP observed by us might to be an expression of a divergence between actual tobacco smoke exposure and its assessment based on level of habitual cigarette consumption. It is possible that smokers titrate their intake of nicotine, taking more nicotine per cigarette when smoking fewer compared to a greater number of cigarettes. Naturally, it is not possible to infer causal relations from cross-sectional results such as those presented here. However, our observations suggest a possible dose dependence of the relationship between BP and both cigarette and coffee consumption. Our observations relate the medium/long-term effects of habitual cigarette and coffee consumption to BP, evaluated as 'basal' BP. BP levels during the day have to be considered before inferences on the eventual consequences of smoking or coffee consumption, resulting from prolonged but reversible variations of BP levels, can be made. In fact, we cannot extrapolate from BP values recorded in abstinent smokers to BP during the average day. Smoking individual cigarettes may only increase BP for 30-60 minutes, but daily cigarette consumption may to be enough to significantly raise average BP levels during the day. Thus, our observation of normal BP, or even lower than normal, in smokers suggests an integrity of hemostatic mechanisms to counter (short-term) cigarette-induced blood pressure elevation. It may be a temporary 'reset' of BP since 'basal' blood pressure tends to rise when smokers give up the habit (9). The same is also theoretically valid for coffe consumers, even if a recent study found that caffeine increased BP only in nontolerant subjects but had little effect on BP in regular coffee drinkers (21). Relationships that involve coffee consumption in Italian subjects are particularly interesting given that the typical Italian brewing method is vaporisation under pressure, the so-called 'espresso' (15), a method different from those used in other countries, such as filtering or boiling. Water (the extracting liquid) is brought to a temperature slightly higher than the boiling point and is passed through a bed of coffee placed on a filter. Thus, the water temperature is higher than in both boiling and filtering under gravity methods (and its variants, notably filtration under pressure and filtration with recirculation, as used in 'percolators') (4). However, extraction time, about 100 seconds, is brief. Finally, the 'consumption of cigarettes' and the 'consumption of coffee' appear heavily associated (X2test for independence of the subjects' classification by smoking and coffee consumption: men, Table 3, P < 0.0001; women, Table 4, P < 0.0001). Experimental observations showed a larger and sustained 'hypertensive' effect of contemporary coffee and cigarette consumption than either stimulus alone (10). However, caffeine would be able to inhibit the hypertensive activity of nicotine 'in acuto' (24), and an accelerated catabolism of caffeine is reported in smokers (23).
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In our observations, all interactive terms, relative to an eventual interaction between coffee and cigarette consumption with respect to BP levels, were not significant (Table 6). Thus, smoking and coffee consumption appear to be associated with BP levels according to an additive model. It is possible that eventual chronic effects of cigarette and coffee are produced independently, as well as eliminate a possible interactive effect. Our observations have confirmed, in Italian subjects, the inverse relationships between cigarette and coffee consumption and BP. Some important details were analyzed in depth. Thus, a substantial independence between chronic effects o f coffee consumption and smoking on BP was demonstrated. Moreover, unlike some observations (11, 18), even if weight (BMI) is taken into account in a complex fashion (relating it to BP by linear and quadratic terms and considering eventual interactions with age), we found that the relationship between cigarette and coffee consumption and BP do not disappear.
Acknowledgements We acknowledge with thanks the most constructive comments and suggestions of the anonymous reviewers.
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