Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects

1476-7120-6-9 1476-7120 Research Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects Giacomin Elisa elisagiacomin@libero.it Palmerini Elisabetta elisabettapalmerini@interfree.it Ballo Piercarlo pcballo@tin.it Zacà Valerio valezeta@libero.it Bova Giovanni giovanni.bova@libero.it Mondillo Sergio mondillo@unisi.it

Department of Cardiovascular Disease, University of Siena, Italy

Cardiology Operative Unit, S. Andrea Hospital, La Spezia, Italy

Cardiovascular Ultrasound 1476-7120 2008 6 1 9 http://www.cardiovascularultrasound.com/content/6/1/9 18318902 10.1186/1476-7120-6-9 25 12 2007 04 3 2008 04 3 2008 2008 Giacomin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Few data exist regarding the direct effects of caffeine and smoking on cardiac function. We sought to explore the acute effects of caffeine assumption, cigarette smoking, or both on left ventricular (LV) and right ventricular (RV) function in a population of young normal subjects.

Methods

Forty-five healthy subjects aged 25 ± 2 years underwent echocardiography. Fifteen of them were non-smokers and habitual coffee consumers (group 1), 15 were smokers and not habitual coffee consumers (group 2), and 15 were smokers and habitual coffee consumers (group 3). Peak systolic (S_a), early diastolic E_a, and late diastolic (A_a) velocity of mitral annulus were measured by pulsed Tissue Doppler, and left atrioventricular plane displacement was determined by M-mode. Tricuspid annular velocities and systolic excursion (TAPSE) were also determined. Measurements were performed at baseline and after oral assumption of caffeine 100 mg in group 1, one cigarette smoking in group 2, and both in group 3.

Results

No changes in ventricular function were observed in group 1 after caffeine administration. In group 2, cigarette smoking yielded an acute increase in mitral A_a(+12.1%, p = 0.0026), tricuspid S_a(+9.8%, p = 0.012) and TAPSE (+7.9%, p = 0.017), and a decrease in the mitral E_a/A_aratio (-8.5%, p = 0.0084). Sequential caffeine assumption and cigarette smoking in group 3 was associated with an acute increase in mitral A_a(+13.0%, p = 0.015) and tricuspid A_a(+11.6%, p < 0.0001) and a reduction in mitral E_a/A_aratio (-8.5%, p = 0.0084) tricuspid E_a(-6.6%, p = 0.048) and tricuspid E_a/A_aratio (-9.6%, p = 0.0003). In a two-way ANOVA model controlling for hemodynamic confounding factors, changes in the overall population remained significant for mitral A_aand E_a/A_aratio, and for tricuspid A_aand E_a/A_aratio.

Conclusion

In young healthy subjects, one cigarette smoking is associated to an acute impairment in LV diastolic function and a hyperdynamic RV systolic response. Caffeine assumption alone does not exert any acute effect on ventricular long-axis function, but potentiates the negative effect of cigarette smoking by abolishing RV supernormal response and leading to a simultaneous impairment in both LV and RV diastolic function.

Background

Both caffeine assumption and cigarette smoking are well known to yield considerable changes in cardiovascular hemodynamics. Increases in blood pressure and heart rate related to dietary intake of caffeine and cigarette smoking 123 as well as reductions after short-time abstinence 45 have been previously reported. Caffeine assumption has also been shown to acutely increase both systolic and diastolic blood pressure 6 with no significant changes in heart rate 78, whereas an adrenergic-mediated acute increase in blood pressure and heart rate has been observed after cigarette smoking 9. Moreover, available data support the hypothesis that caffeine assumption and cigarette smoking may show synergistic effects on the hemodynamic status 1011.

Nonetheless, few evidences exist regarding the direct effects of caffeine and smoking on cardiac function. Studies on animal models suggest that intravenous caffeine may acutely affect left ventricular (LV) relaxation without altering contractility 12, although a depression in invasively determined indices of systolic and diastolic LV function has been observed after intracoronary administration 13. Caffeine was found to have no effects on standard indices of diastolic and short-axis systolic function after oral administration in humans 14. Both acute and chronic smoking have been reported to induce LV diastolic impairment in normal subjects 1516, an effect that seems to be more evident in type-2 diabetes patients 17. Abnormalities in right ventricular (RV) diastolic performance after acute or chronic exposition to cigarette smoke have also been reported 1819. However, whether caffeine administration and cigarette smoking may have a synergistic impact on LV cardiac function has never been assessed.

The aim of this study was to analyze the acute effects of caffeine assumption, cigarette smoking, or both, on LV and RV performance in a population of young healthy subjects.

Methods

Study population

The study population included a total of 45 young healthy volunteers (mean age 25 ± 2 years) free of cardiovascular or systemic diseases. Of them, 15 were non-smokers and habitual coffee consumers (group 1), 15 were smokers and not habitual coffee consumers (group 2), and 15 were smokers and habitual coffee consumers (group 3). Ten non-smokers and non habitual coffee consumers were considered as controls. None of patients were assuming any medication.

Study protocol

Baseline measurements

Informed written consent for the participation to the study was obtained from all participants. All subjects were asked to abstain from smoking, coffee, and other foods or beverages containing caffeine (e.g., tea, cola, cacao, guarana) for a wash-out period of at least 12 hours before examinations. Baseline systolic blood pressure, diastolic blood pressure, and heart rate were measured after 5 minutes of resting in the supine position, using standard procedures. Arterial oxygen saturation was also measured using a digital pulse oximeter.

Echocardiographic examinations were performed using high-quality machines (Vivid 7, GE, USA) equipped with 2.5 MHz probes. LV diameters and thicknesses, LV mass, end-diastolic LV relative wall thickness, end-diastolic RV diameter were determined in accordance with current ASE recommendations 20. LV volumes, stroke volume, and ejection fraction were measured using the biplane modified Simpson's method. Left atrial volume was obtained from apical views using the biplane method of discs. Pulsed Doppler interrogation of mitral inflow was performed to measure peak early diastolic velocity (E), peak late diastolic velocity (A), their ratio E/A, E wave deceleration time, and isovolumic relaxation time. Mitral annulus velocities were measured using pulsed Tissue Doppler by positioning a 5 mm-sample volume at the level of septal, lateral, inferior and anterior annulus, in accordance with current ASE recommendations 21. Particular care was given to adjust filter and gain settings at the minimal level to obtain the maximal signal-to-noise ratio. The average value of peak systolic (S_a), early diastolic (E_a), and late diastolic (A_a) mitral annulus velocities were determined. The E_a/A_aand E/E_aratios were calculated, and used as indices of LV filling pressures 222324. Pulsed Tissue Doppler imaging of the lateral tricuspid annulus was also performed, and peak systolic, early diastolic, and late diastolic velocities were measured. Two-dimensionally guided M-mode imaging of septal, lateral, inferior, and anterior mitral annulus motion was performed from the apical 4-chamber view, using the zoom function. Total amplitude of systolic annular excursion was measured from the nadir of M-mode profile – corresponding to the point furthest from LV apex – to the point of maximal excursion towards LV apex 25. Left atrioventricular plane displacement (AVPD) was determined by averaging excursion amplitudes recorded at the four annular sites. Tricuspid annular plane systolic excursion (TAPSE) was also measured using two-dimensionally guided M-mode imaging from the apical 4-chamber view. For both Tissue Doppler and M-mode imaging, careful alignment of the ultrasonic beam with annular motion was obtained. All measurements were obtained by averaging values recorded in three consecutive cycles, at a sweep speed of 100 mm/s.

Caffeine assumption and cigarette smoking

The study design is summarized in Figure 1. At the end of baseline evaluation, subjects in group 1 were asked to assume caffeine 100 mg administered orally (galenic preparation solved in 40 ml of water), a dosage that is equivalent to that of an express coffee. Subjects in group 2 were asked to smoke one cigarette in 5 minutes. Subjects in group 3 were asked to assume caffeine 100 mg per os, to wait for 30 minutes, and then to smoke one cigarette in 5 minutes. Cigarettes used for groups 2 and 3 contained nicotine 0.9 mg, carbon monoxide 10 mg, and tar 10 mg, and were of the same brand (Camel).

Figure 1

Study design

Study design.

A second clinical and echocardiographic examination was performed after a total of 45 minutes from caffeine assumption in group 1, after 15 minutes from beginning of cigarette smoking in group 2, and after 45 minutes from caffeine assumption (i.e., 15 minutes from beginning of cigarette smoking) in group 3. During these periods, patients were asked to rest quiet in the sitting position. The second examination included measurement of systolic blood pressure, diastolic blood pressure, heart rate, arterial oxygen saturation, mitral inflow indices, mitral annulus velocities and AVPD averaged over four annular sites, lateral tricuspid annulus velocities, and TAPSE.

The experimental setting (Figure 2) included a smoking room and a standing room, both characterized by quiet and comfortable environments. The smoking room was only used by patients in group 2 and 3 for 5 minutes during cigarette smoking. The standing room was used for all other protocol intervals.

Figure 2

Experimental setting of the study

Experimental setting of the study. Caffeine in group 1 and 3 was administered within the Echo Lab, at the end of basal examination.

Statistical analysis

Data were expressed as mean ± standard deviation. Between-group comparisons at baseline were performed using the Kruskal-Wallis test for continuous variables and the chi-square test for categorical variables. Within-group comparisons between baseline values and those obtained after caffeine assumption, cigarette smoking, or both were performed using the Student t test for paired samples. Repeated measures two-way ANOVA was also performed by considering groups and status (i.e., baseline or after testing) as the main variables within a 3 × 2 factorial design, using a mixed model adjusting for heart rate, systolic blood pressure, and diastolic blood pressure. The P value for the main effect of status was used to express the significance of the effect of caffeine and smoking on ventricular function in the overall population, whereas the interaction P value was considered to explore for differences in the effect of testing across groups. A P value < 0.05 was considered for statistical significance. All tests were two-tailed. Analyses were performed using the SPSS (Statistical Package for the Social Sciences, Chicago, Illinois) software Release 11.5.

Results

Baseline clinical and echocardiographic characteristics were similar among the four study groups (Table 1). Changes in clinical variables and mitral flow Doppler indices after caffeine assumption, cigarette smoking, or both in comparison with baseline are shown in Table 2. An increase in systolic blood pressure, diastolic blood pressure, and heart rate was observed in group 2. An isolated increase in heart rate was found in group 3, whereas no changes were noted in group 1.

Table 1

General characteristics of the study groups. Comparison of clinical and echocardiographic features among the four study groups.

Controls

Coffee assumption

Cigarette smoking

Coffee assumption + cigarette smoking

ANOVA P value

Age (years)

24.1 ± 1.7

25.3 ± 4.3

24.9 ± 2.7

23.6 ± 2.5

0.68

Male gender (n)

6 (60%)

9 (60%)

6 (40%)

9 (60%)

0.68

BMI (Kg/m²)

20.2 ± 2.1

20.7 ± 5.5

21.0 ± 1.7

22.0 ± 2.4

0.38

Coffees (n/die)

2.5 ± 1.1

3.0 ± 2.4

0.28*

Cigarettes (n/die)

8.4 ± 5.3

11.7 ± 5.1

0.09*

Years of smoking (n)

7.5 ± 3.8

8.1 ± 2.7

0.66*

SBP (mmHg)

116.0 ± 8.1

125 ± 9.6

116.7 ± 12.8

122.3 ± 2.5

0.11

DBP (mmHg)

75.0 ± 5.8

76.7 ± 9.6

75.0 ± 11.2

79.7 ± 7.9

0.50

Heart rate (bpm)

74.9 ± 10.0

74.5 ± 10.6

72.7 ± 11.4

66.1 ± 9.4

0.15

O₂saturation (%)

97.5 ± 1.2

97.6 ± 0.7

97.9 ± 0.7

97.5 ± 0.9

0.77

LVEDV (ml)

89.0 ± 28.2

99.7 ± 28.3

89.4 ± 14.2

92.9 ± 29.5

0.84

Ejection fraction (%)

67.4 ± 3.2

64.8 ± 3.6

64.2 ± 5.5

63.8 ± 4.8

0.14

Stroke volume (ml)

60.0 ± 18.5

66.4 ± 23.0

57.8 ± 5.5

59.2 ± 17.4

0.89

LV mass (g)

126.6 ± 31.4

132.0 ± 45.1

122.1 ± 22.5

143.2 ± 40.0

0.40

RWT

0.32 ± 0.05

0.34 ± 0.05

0.34 ± 0.07

0.82

Left atrial volume (ml)

42.6 ± 11.4

38.8 ± 16.2

34.0 ± 7.5

38.6 ± 10.4

0.34

RV diameter (mm)

30.7 ± 4.2

31.3 ± 5.4

29.3 ± 4.3

31.12 ± 4.3

0.60

PASP (mmHg)

20.5 ± 2.7

21.9 ± 3.6

21.6 ± 3.4

21.2 ± 4.5

0.66

E (cm/s)

80.2 ± 19.3

92.1 ± 14

89.1 ± 14.8

84.1 ± 13.0

0.32

A (cm/s)

52.2 ± 15.5

54.2 ± 11

53.9 ± 8.9

48.2 ± 13.2

0.42

E/A ratio

1.6 ± 0.3

1.8 ± 0.4

1.7 ± 0.4

1.9 ± 0.5

0.47

Deceleration time (ms)

209.8 ± 32.7

201.9 ± 50.3

202.5 ± 35.9

216.9 ± 34.8

0.70

IVRT (ms)

62.2 ± 9.4

67.6 ± 12.8

67.1 ± 10.7

63.1 ± 10.4

0.49

BMI = body mass index. SBP = systolic blood pressure; DBP = diastolic blood pressure; LVEDD = left ventricular end-diastolic diameter; LV = left ventricular; RWT = relative wall thickness; RV = right ventricular; PASP = pulmonary artery systolic pressure; IVRT = isovolumic relaxation time.

*P values for comparison of variables between two groups calculated by Student t test for unpaired data

Table 2

Clinical variables and mitral inflow after coffee assumption, cigarette smoking, or both. Comparison of clinical and echocardiographic characteristics among groups after coffee assumption, cigarette smoking, or both. Abbreviations are the same used in Tables 1–2.

Coffee assumption

Cigarette smoking

Coffee assumption and cigarette smoking

Adjusted overall P value^b

Interaction P value^c

Change from baseline

P value^a

Change from baseline

P value^a

Change from baseline

P value^a

SBP (mmHg)

+1.2%

0.43

+8.6%

0.0010

+4.8%

0.17

DBP (mmHg)

+3.2%

0.24

+7.6%

0.013

+3.3%

0.30

HR (bpm)

-3.2%

0.19

+18.7%

< 0.0001

+14.5%

< 0.0001

SO₂(%)

-0.2%

0.63

0.3%

0.36

+0.2%

0.58

0.62

0.52

E (cm/s)

-6.1%

0.11

+2.6%

0.80

+0.7%

0.99

0.26

0.15

A (cm/s)

-8.3%

0.06

-2.0%

0.79

+9.3%

0.81

0.29

0.22

E/A ratio

+4.8%

0.19

+10.8%

0.49

-2.7%

0.71

0.68

0.39

DT (ms)

+5.1%

0.99

-1.9%

0.76

-7.8%

0.15

0.34

0.28

IVRT (ms)

+3.8%

0.60

+7.1%

0.41

+5.1%

0.36

0.28

0.92

^aCalculated by within-group comparison with baseline value

^bP value for the overall effect of testing in the entire population, as determined by two-way ANOVA using a mixed model adjusting for heart rate and blood pressure

^cP value for differences in the effect of testing across groups, as determined by two-way ANOVA in a mixed model adjusting for heart rate and blood pressure

At within-group analysis, caffeine assumption in group 1 did not yield any change in any of the analyzed variables (Figures 3, 4, top panels). In group 2, an increase in mitral A_a, tricuspid S_a, and TAPSE, and a reduction in the mitral annulus E_a/A_aratio were observed after cigarette smoking (Figures 3, 4, middle panels). In group 3, an increase in mitral A_aand tricuspid A_a, and a reduction in mitral E_a/A_aratio, tricuspid E_a, and tricuspid E_a/A_aratio were observed after sequential caffeine assumption and cigarette smoking (Figures 3, 4, bottom panels).

Figure 3

Relative changes in left ventricular long-axis function after caffeine assumption, cigarette smoking, or both

Relative changes in left ventricular long-axis function after caffeine assumption, cigarette smoking, or both. P values are calculated by within-group Student t test for paired data. S_m= peak systolic mitral annulus velocity; E_m= peak early diastolic mitral annulus velocity; A_m= peak late diastolic mitral annulus velocity; E = peak early diastolic transmitral flow; AVPD = left atrioventricular plane displacement.

Figure 4

Relative changes in right ventricular long-axis function after caffeine assumption, cigarette smoking, or both

Relative changes in right ventricular long-axis function after caffeine assumption, cigarette smoking, or both. P values are calculated by within-group Student t test for paired data. S_m= peak systolic tricuspid annulus velocity; E_m= peak early diastolic tricuspid annulus velocity; A_m= peak late diastolic tricuspid annulus velocity; TAPSE = tricuspid annular plane systolic excursion.

In a two-way ANOVA model adjusting for hemodynamic confounding factors, changes in long-axis function observed in the overall population remained significant for mitral A_a(p = 0.0014) and E_a/A_aratio (p = 0.0022), and for tricuspid A_a(p = 0.010) and E_a/A_aratio (p = 0.019). For these 4 variables, significant interaction P values were found (p = 0.0009, p = 0.0003, p < 0.0001, and p = 0.0006, respectively), suggesting differences in the effect of testing across groups. Significant interaction P values were also observed for tricuspid S_a(p = 0.038) and TAPSE (p = 0.049).

Discussion

The results of this study show that: 1) caffeine assumption does not yield any significant change in ventricular long-axis function; 2) cigarette smoking is associated with an acute impairment in LV diastolic function and an increase in RV long-axis systolic indices; 3) caffeine assumption followed by cigarette smoking is associated with an acute impairment in both LV and RV diastolic function.

The absence of significant effects of caffeine administration on LV long-axis indices observed in this study confirms early reports that found no effects on standard indices of LV systolic and diastolic function 26, and strengthens this hypothesis by showing that functional changes after caffeine assumption cannot be detected even when sensitive indices of ventricular function are considered. The evidence of changes in diastolic long-axis indices after cigarette smoking is also in accordance with current available data 1627. Of note, in our population most of this effect was driven by an increase in the late diastolic component of mitral annulus motion (Figure 5, top panels), with only a nonsignificant trend towards a reduction in the early diastolic component. This resulted in a 12% reduction in the mitral E_a/A_aratio – an index of LV diastolic function that correlates with LV filling pressures 23. Moreover, in this study caffeine assumption followed by cigarette smoking was associated with an increase in mitral A_aand a reduction in the E_a/A_aratio similar to that observed after cigarette smoking alone (Figure 6, top panels). This may indicate that caffeine assumption does not alter the acute effect of cigarette smoking on LV function, suggesting that the synergistic effect between smoke and caffeine previously demonstrated for blood pressure 112829 cannot be extended to LV function.

Figure 5

Tissue Doppler pattern of mitral annulus motion and M-mode imaging of tricuspid annulus motion at baseline (panels A-C) and after cigarette smoking (panels B-D), showing an increase in mitral peak A_mvelocity and tricuspid annular plane systolic displacement (TAPSE)

Figure 6

Tissue Doppler pattern of mitral and tricuspid annulus motion at baseline (panels A-C) and after coffeine assumption followed by cigarette smoking (panels B-D), showing an increase in both mitral and tricuspid peak A_mvelocities

Considering that nicotine gum chewing does not yield any acute change in LV diastolic performance in young healthy individuals 30, it is likely that the acute effect of smoking on LV diastolic function may not be due to nicotine alone. A potential role of smoke-induced acute impairment in coronary blood flow could be hypothesized 2631. Additionally, the absence of significant changes in the E/E_aratio – a powerful index of LV filling pressure 24 – suggests the effective mechanisms underlying the observed changes in diastolic mitral annulus velocities deserve further investigations.

In this study, caffeine assumption showed no acute effect on RV function as well. In contrast, cigarette smoking was associated with an acute increase in indices of RV long-axis systolic function (Figure 5, bottom panels). It could be hypothesized that this effect may represent the consequence of an acute adrenergic stimulus induced by nicotine 3233. Nonetheless, an interaction between neuroendocrine factors and variations in RV afterload due to acute changes in the vascular tone at the level of pulmonary vascular bed 19 cannot be excluded. Intriguingly, the hyperdynamic response of RV long-axis systolic function was no longer evident in patients assuming caffeine prior to cigarette smoking. Moreover, in these subjects an impairment of RV diastolic indices, characterized by an increase in the late diastolic component of tricuspid annulus motion and a reduction in the tricuspid E_m/A_mratio, was observed (Figure 6, bottom panels). The mechanisms underlying these changes are worthy of further exploration. However, these results may suggest that caffeine and cigarette smoking could exert a synergistic negative effect on RV function.

The findings of this study further highlight the importance of smoking as a cardiovascular risk factor, by pointing out that its well-known deleterious effects on the cardiovascular system include a depression in LV diastolic performance that is already evident few minutes after smoking a single cigarette. Moreover, the evidence that the association of caffeine administration and cigarette smoking resulted in simultaneous impairment in both LV and RV diastolic function suggests that concomitant assumption of coffee (or other food or beverages containing caffeine) and cigarette smoking should be avoided.

This study has limitations. A lager sample size would have added statistical solidity to our results. The study population included young healthy subjects, so that caution is required in extending results to other populations. The choice of an interval of 45 minutes between baseline and second examination in group 1 and 3 was based on a general estimate of the time necessary to reach the peak plasmatic concentration of caffeine after oral assumption, but a considerable inter-individual variability in caffeine kinetics exists 34. Similar considerations can be made for the arbitrary choice of an interval of 15 minutes after the beginning of smoking. Assessment of LV and RV diastolic function was performed using Tissue Doppler indices, but further studies on invasively determined measures of ventricular function are needed.

Conclusion

In summary, one cigarette smoking acutely impairs LV diastolic function and is associated to a hyperdynamic RV systolic response in young normal subjects. Concomitant caffeine assumption may enhance the negative effect of cigarette smoking by abolishing RV hyperdynamic response and favouring simultaneous impairment in both LV and RV diastolic performance.

Competing interests

The author(s) declare that they have no competing interests.

Authors' contributions

All authors participated to the design of the study. EP, EG, GB, and VZ were responsible for collection of data and drafting of manuscript. PB performed the statistical analysis and revised the manuscript critically for important intellectual content. SM conceived the study and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Critical review of dietary caffeine and blood pressure: a relationship that should be taken more seriously James JE Psychosomatic Medici 2004 66 63 71 10.1097/10.PSY.0000107884.78247.F9 Smoking among patients with malignant hypertension Tuomiletho J Elo J Nissinen A BMJ 1982 1 1086 24-hour ambulatory electrocardiographic registry: differences between smokers and non-smokers and habit breaking effects Aparici M Fernández González AL Peteiro J Med Clin 1993 100 125 127 Effects of coffee on ambulatory blood pressure in older men and women. A randomized controlled trial Rakic V Burke V Beilin LJ Hypertension 1999 33 869 873 10082501 Effects of a 2-day abstinence from smoking on dietary, cognitive, subjective, and physiologic parameters among younger and older female smokers Kos J Hasenfratz M Bättig K Physiol Behav 1997 61 671 678 10.1016/S0031-9384(96)00518-5 9145936 Hypertension risk status and effect of caffeine on blood pressure Hartley TR Sung BH Pincomb GA Whitsett TL Wilson MF Lovallo W Hypertension 2000 36 137 141 10904026 The effects of caffeine in women during aerobic-dance bench stepping Ahrens JN Lloyd LK Crixell SH Walker JL Int J Sport Nutr Exerc Metab 2007 17 27 34 17460331 Effects of caffeine on blood pressure, heart rate, and forearm blood flow during dynamic leg exercise Daniels JW Molé PA Shaffrath JD Stebbins CL J Appl Physiol 1998 85 154 159 9655769 Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events Cryer PE Haymond MW Santiago JV Shah SD N Engl J Med 1976 295 573 577 950972 Combined effects of caffeine and nicotine on cardiovascular hemodynamics in canine model Jain AC Mehta MC Billie M J Cardiovasc Pharmacol 1997 29 574 579 10.1097/00005344-199705000-00002 9213197 Oral caffeine maintenance potentiates the reinforcing and stimulant subjective effects of intravenous nicotine in cigarette smokers Jones HE Griffiths RR Psychopharmacology 2003 165 280 290 12434259 Load dependence of left ventricular contraction and relaxation. Effects of caffeine Leite-Moreira AF Correia-Pinto J Gillebert TC Basic Res Cardiol 1999 94 284 293 10.1007/s003950050154 10505429 Effects of intracoronary caffeine on left ventricular mechanoenergetics in Ca2+ overload failing rat hearts Fujii W Takaki M Yoshida A Ishidate H Ito H Suga H Jpn J Physiol 1998 48 373 381 10.2170/jjphysiol.48.373 9852346 The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease Hirsch AT Gervino EV Nakao S Come PC Silverman KJ Grossman W Ann Intern Med 1989 110 593 598 2930092 Longitudinal diastolic myocardial functions are affected by chronic smoking in young healthy people: a study of color tissue doppler imaging Gulel O Soylu K Yazici M Demircan S Durna K Sahin M Echocardiography 2007 24 494 498 10.1111/j.1540-8175.2007.00421.x 17456068 Acute effects of smoking on diastolic function in healthy participants: studies by conventional doppler echocardiography and doppler tissue imaging Alam M Samad BA Wardell J Andersson E Hoglund C Nordlander R J Am Soc Echocardiogr 2002 15 1232 1237 10.1067/mje.2002.124006 12411910 Differences in the immediate effects of smoking on left ventricular diastolic function between healthy volunteers and patients with type 2 diabetes mellitus Kim HKK Bae W Chung JW Cho YM Kim YJK Sohn DW Park YB J Am Soc Echocardiogr 2005 18 320 325 10.1016/j.echo.2004.10.014 15846158 Chronic and acute effects of smoking on left and right ventricular relaxation in young healthy smokers Lichodziejewska B Kurnicka K Grudzka K Malysz J Ciurzynski M Liszewska-Pfejfer D Chest 2007 131 1142 1148 10.1378/chest.06-2056 17426221 Acute effects of smoking on right ventricular function. A tissue Doppler imaging study on healthy subjects Ilgenli TF Akpinar O Swiss Med Wkly 2007 137 91 96 17370145 Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology J Am Soc Echocardiogr 2005 18 1440 1463 10.1016/j.echo.2005.10.005 16376782 Recommendations for quantification of Doppler echocardiography a report from the Doppler quantification task force of the nomenclature and standard committee of the American Society of Echocardiography Quinones MA Otto CM Waggoner A Zoghbi WA J Am Soc Echocardiogr 2002 15 167 84 10.1067/mje.2002.120202 11836492 Tissue Doppler imaging a new prognosticator for cardiovascular diseases Yu CM Sanderson JE Marwick TH Oh JK J Am Coll Cardiol 2007 49 1903 1914 10.1016/j.jacc.2007.01.078 17498573 Estimation of left ventricular end-diastolic pressure by color M-mode Doppler echocardiography and Tissue Doppler imaging Dagdelen S Eren N Karabulut H Akdemir I Ergelen M Saglam M Yüce M Alhan C Caglar N J Am Soc Echocardiogr 2001 14 951 958 10.1067/mje.2001.113544 11593199 Clinical utility of Doppler echocardiography and Tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study Ommen SR Nishimura RA Appleton CP Miller FA Oh JK Redfield MM Tajik AJ Circulation 2000 102 1788 1794 11023933 Circumferential versus longitudinal systolic function in subjects with hypertension: a nonlinear relation Ballo P Quatrini I Giacomin E Motto A Mondillo S J Am Soc Echocardiogr 2007 20 298 306 10.1016/j.echo.2006.08.024 17336758 The mechanism of action of nicotine on vascular adrenergic neuroeffector transmission Nedergaard OA Schrold J Eur J Pharmacol 1977 42 315 329 10.1016/0014-2999(77)90165-0 192563 Influence of smoking habit on cardiac functional capacity and diastolic function in healthy people Tello A Marin F Roldan V Lorenzo S Molto JM Sogorb F Int J Cardiol 2005 98 517 518 10.1016/j.ijcard.2003.11.025 15708192 The cardiovascular interaction between caffeine and nicotine in humans Smits P Temme L Thien T Clin Pharmacol Ther 1993 54 194 204 8354027 Smoking and caffeine have a synergistic detrimental effect on aortic stiffness and wave reflections Vlachopoulos C Kosmopoulou F Panagiotakos D Ioakeimidis N Alexopoulos N Pitsavos C Stefanadis C J Am Coll Cardiol 2004 44 1911 1917 10.1016/j.jacc.2004.07.049 15519028 Acute changes in left ventricular diastolic function: cigarette smoking versus nicotine gum Gembala MI Ghanem F Mann CA Sorrell VL Clin Cardiol 2006 29 61 4 10.1002/clc.4960290205 16506640 Changes of diastolic function induced by cigarette smoking: an echocardiographic study in patients with coronary artery disease Störk T Eichstädt H Möckel M Bortfeldt R Müller R Hochrein H Clin Cardiol 1992 15 80 86 1737409 Smoking-induced coronary vasoconstriction in patients with atherosclerotic coronary artery disease: evidence for adrenergically mediated alterations in coronary artery tone Winniford MD Wheelan KR Kremers MS Ugolini V van den Berg E Jr Niggemann EH Jansen DE Hillis LD Circulation 1986 73 662 667 3948369 Tobacco: a precipitating factor in angina pectoris Aronow WS Kaplan MA Jacob D Ann Intern Med 1968 69 529 536 5673171 Hemodynamic effects of "expresso" Italian coffee and pure caffeine on healthy volunteers Casiglia E Paleari CD Daskalakis C Petucco S Bongiovi S Pessina AC Cardiologia 1990 35 575 580 2088602