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(Hypertension. 1999;33:586-590.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effects of Smoking Cessation on Blood Pressure and Heart Rate Variability in Habitual Smokers

Junichi Minami; Toshihiko Ishimitsu; Hiroaki Matsuoka

From the Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.

Correspondence to Junichi Minami, MD, Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. E-mail j-minami{at}dokkyomed.ac.jp

	Abstract

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Abstract—We investigated the effects of 1-week of smoking cessation on ambulatory blood pressure, heart rate, and heart rate variability in 39 normotensive male habitual smokers (mean±SEM, 32.5±1.0 years). The ambulatory blood pressure, heart rate, and ECG R-R intervals were measured during a 24-hour period with a portable recorder (TM-2425) on the last day of 1-week smoking and nonsmoking periods. The order of the 2 periods was randomized. In the smoking period, the subjects were instructed to smoke cigarettes according to their usual smoking patterns. A power-spectral analysis of R-R intervals was performed to obtain the low-frequency (LF) and high-frequency (HF) components. The percentage of differences between adjacent normal R-R intervals >50 milliseconds (pNN50) was used as a time-domain measure of heart rate variability. The 24-hour ambulatory blood pressure was significantly lower in the nonsmoking period than in the smoking period, by 3.5±1.1 mm Hg systole [P<0.01] and by 1.9±0.7 mm Hg diastole [P<0.05], whereas the nighttime blood pressure did not differ significantly between the 2 periods. The 24-hour heart rate was significantly lower in the nonsmoking period than in the smoking period, by 7.3±1.0 beats/min (P<0.0001). The pNN50 and the 24-hour HF component were significantly higher in the nonsmoking period than in the smoking period (P<0.0001 for each). The plasma norepinephrine and epinephrine concentrations were significantly lower in the nonsmoking period than in the smoking period (P<0.05 for each). These results demonstrate the substantial and immediate benefits of smoking cessation on these cardiovascular indices.

Key Words: smoking cessation • blood pressure monitoring, ambulatory • heart rate • heart rate variability • sympathetic nervous system • parasympathetic nervous system

	Introduction

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Cigarette smoking is one of the strongest contributors to the risks of cardiovascular diseases, including coronary heart disease, stroke, sudden death, peripheral artery disease, and aortic aneurysm.¹ Considerable reductions in the risk of cardiovascular diseases occur immediately after the discontinuation of cigarette smoking.² Alterations in blood pressure (BP), heart rate (HR), and autonomic nervous function are thought to be at least in part responsible for the rapid reduction in the risk of cardiovascular diseases after quitting. However, no randomized trials have assessed the effects of smoking cessation on these factors simultaneously in the same individuals. Regarding smoking cessation–induced changes in 24-hour BPs, no investigations have been performed in the manner of interventional trials. To obtain conclusive information on these issues, we investigated the effects of short-term smoking cessation on 24-hour BP, HR, and heart rate variability (HRV) and plasma catecholamine levels in a considerable number of male habitual smokers.

	Methods

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Subjects
We studied 42 normotensive healthy Japanese men who were all habitual cigarette smokers (10 cigarettes daily; range 10 to 80) and stated their desire to stop smoking. The mean±SEM age was 32.8±1.1 years. They all agreed to participate in the study after receiving a detailed explanation of its nature and purpose, and each subject gave written informed consent. The study protocol was in accordance with the Declaration of Helsinki (1989) of the World Medical Association and was approved by the institutional review board of Dokkyo University School of Medicine.

Study Protocol
The subjects were randomly allocated to 1 of 2 experimental groups. Members of the first group (n=19) were instructed to cease smoking for 1 week (nonsmoking period). At the end of this period, subjects resumed their usual smoking with their usual pattern of smoking for another 1 week period (smoking period). Members of the second group (n=23) were allocated to a reverse study design; they continued their usual smoking habits and usual patterns of smoking during the first week (smoking period) and were instructed to cease smoking for the second week (nonsmoking period). During the first 3 days of the nonsmoking periods, all subjects were strongly encouraged, via telephone conversations, to maintain the cessation of smoking.

Blood Sampling and Analysis
Venous blood samples were obtained after a 12-hour overnight fast from subjects after 15 minutes of supine rest on the last day of each period. Plasma catecholamine levels were measured with high-performance liquid chromatography. Serum nicotine and cotinine concentrations were measured with gas chromatographiy as described by Jacob et al.³ Cotinine, a metabolite of nicotine, has a much longer half-life and fluctuates much less throughout the day than does nicotine and is widely used as a marker of daily nicotine intake.⁴ We used cotinine to assess compliance with the cessation protocol.

24-Hour Ambulatory Blood Pressure Measurement
The ambulatory BP was monitored every 30 minutes by a cuff-oscillometric device (model TM-2425; A&D Co)⁵ on the last day of each period. The subjects were asked to carry the device for 26 hours, and the first 2 hours of recordings made at or near the hospital were omitted from the analysis. The ambulatory monitoring was performed during an average working day. The TM-2425 contains an acceleration sensor in the main unit⁵ ; the subject's physical activity was quantified every 1 minute. The subject was requested to note his activities in a miniature diary with particular attention to times of retiring to bed and arising in the morning. The daytime and nighttime BPs were calculated according to the true waking and sleeping times of the individual subjects. The subject was also requested to note the number of cigarettes smoked per hour in the diary during the smoking period. The same recorder was used for each subject for the entire protocol to avoid having different BP readings obtained by different recorders.

Power-Spectral Analysis of R-R Intervals
The ambulatory BP recorder used in this study, the TM-2425, also monitored the R-R interval of the electrocardiogram (ECG). The procedures for determining the power-spectral analysis of R-R intervals in this device were previously reported in detail by our group.⁶ Spectral R-R interval variability was computed as the LF component (0.05 to 0.15 Hz) and HF component (0.15 to 0.40 Hz) with the autoregressive model from every 5-minute block over a 24-hour period. The LF/HF ratio was calculated as an index of sympathovagal balance,⁷ although there are some problems with the interpretation of this index.⁸ We also calculated 1 of the time domain indices, pNN50, which is the percentage of differences between adjacent normal R-R intervals >50 milliseconds; the pNN50 is a useful marker of parasympathetic nerve activity.⁹ HR was calculated on the basis of continuous ECG recordings.

Statistical Analysis
Values are expressed as means±SEM. Comparisons between the smoking and nonsmoking periods were made using Student's paired t test and 1-way repeated measures ANOVA as appropriate. Newman-Keuls tests were used as determined by the ANOVA results. For the comparisons of power-spectral data, the natural logarithmic values, ie, ln (the LF component), ln (the HF component), or ln (the LF/HF ratio), were used to normalize the skewness of the data. Statistical significance was accepted at the level of P<0.05.

	Results

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Of the 42 subjects, 3 resumed smoking during the nonsmoking period. Therefore, we analyzed the data of the remaining 39 subjects. Their baseline characteristics are shown in Table 1.

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics of Study Subjects

Effects of Smoking Cessation on Body Weight and Laboratory Data
Table 2 lists the average values of body weight, serum nicotine and cotinine concentrations, and plasma norepinephrine and epinephrine concentrations during the smoking and nonsmoking periods. The subjects' body weights did not differ significantly between the 2 periods. The serum nicotine and cotinine concentrations were significantly lower in the nonsmoking period than in the smoking period. The plasma norepinephrine and epinephrine concentrations were also significantly lower in the nonsmoking period than in the smoking period.

View this table: [in this window] [in a new window]   Table 2. Body Weight, Serum Nicotine and Cotinine Concentrations, and Plasma Norepinephrine and Epinephrine Concentrations During the Smoking and Nonsmoking Periods

Effects of Smoking Cessation on 24-Hour BP and HR
Figure 1 depicts the 24-hour trends of BP and HR in each period and the average number of cigarettes smoked per hour in the smoking period. Table 3 lists the average values of BP, HR, and physical activity for the entire 24-hour period, the daytime, and the nighttime. Physical activity quantified by an acceleration sensor did not differ significantly between the 2 periods in the daytime or the nighttime. The daytime BP was significantly lower in the nonsmoking period than in the smoking period, by 4.9±1.2 mm Hg systole (P<0.001) and 2.7±0.8 mm Hg diastole (P<0.01), whereas the nighttime BP did not differ significantly between the 2 periods. The difference in the 24-hour BP between the 2 periods was 3.5±1.1 mm Hg systole (P<0.01) and 1.9±0.7 mm Hg diastole (P<0.05). With regard to the HR, not just the daytime HR but also the nighttime HR was significantly lower in the nonsmoking period than in the smoking period, by 9.2±1.1 beats/min (P<0.0001) and by 3.7±1.2 beats/min (P<0.01), respectively. The difference in the 24-hour HR between the 2 periods was 7.3±1.0 beats/min (P<0.0001). The number of total heart beats over 24 hours was 118 919±2 017 in the smoking period and 108 448±2 065 in the nonsmoking period (P<0.0001).

View larger version (22K): [in this window] [in a new window]   Figure 1. The 24-hour trends of BP and HR during the smoking () and nonsmoking () periods and the average number of cigarettes smoked per hour in the smoking period. The daytime BP was significantly lower in the nonsmoking period than in the smoking period, whereas the nighttime BP did not differ significantly between the 2 periods. The daytime and nighttime HR values were significantly lower in the nonsmoking period than in the smoking period.

View this table: [in this window] [in a new window]   Table 3. BP, HR, and Physical Activity During the Smoking and Nonsmoking Periods

Effects of Smoking Cessation on Measures of HRV
Table 4 lists the average values of the pNN50, the LF component, the HF component, and the LF/HF ratio for the entire 24-hour period, the daytime and the nighttime. Figure 2 depicts the 24-hour trends of the LF component, the HF component, and the LF/HF ratio in each period and the average number of cigarettes smoked per hour in the smoking period. The pNN50 and the HF component both were significantly higher in the nonsmoking period than in the smoking period in both the daytime and nighttime, indicating that the smoking cessation augmented the parasympathetic nerve activity throughout a 24-hour period in these subjects. The daytime LF/HF ratio was significantly lower in the nonsmoking period than in the smoking period (P<0.01), whereas the nighttime LF/HF ratio did not differ significantly between the 2 periods.

View this table: [in this window] [in a new window]   Table 4. Time Domain and Frequency Domain Measures of HRV During the Smoking and Nonsmoking Periods

View larger version (22K): [in this window] [in a new window]   Figure 2. The 24-hour trends of the LF component, the HF component, and the LF/HF ratio during the smoking () and nonsmoking () periods and the average number of cigarettes smoked per hour in the smoking period. The LF and HF components both were significantly higher in the nonsmoking period than in the smoking period in both the daytime and nighttime. The daytime LF/HF ratio was significantly lower in the nonsmoking period than in the smoking period, whereas the nighttime LF/HF ratio did not differ significantly between the 2 periods.

	Discussion

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The data obtained in this study demonstrate that the short-term smoking cessation produced reductions in ambulatory BP, HR, and sympathetic nerve activity and an augmentation of parasympathetic nerve activity in male habitual smokers with normal BPs. Although the decrease in the nighttime BP was not prominent compared with that in the daytime BP, the 24-hour BP level was significantly decreased by the 1-week smoking cessation. In addition, decreases in the HR and the parasympathetic nerve activity were observed throughout a 24-hour period, and even in the nighttime.

This is the first study in which the effect of smoking cessation on ambulatory BP was examined over 24 hours by the use of intervention and a randomized trial in the same individuals. Several investigators have shown, in a cross-sectional comparison of habitual smokers and nonsmoking controls, that daytime ambulatory BP is significantly higher in smokers than in nonsmokers, whereas nighttime BP does not differ significantly between the 2 groups.^{10 11} The present study confirms these earlier findings with a randomized crossover design.

As for the effect of smoking on HRV, a few investigators have shown that HRV is lower in smokers than in nonsmokers on the basis of a cross-sectional comparison of habitual smokers and nonsmoking controls.^{12 13 14} There are 2 studies to date that assessed changes in HRV after smoking cessation; however, their findings are not completely consistent with each other. According to Stein et al,¹⁵ all time and frequency domain indices of HRV were significantly elevated after 4 weeks of smoking cessation, although the LF/HF ratio was not affected. In contrast, Yotsukura et al¹⁶ have recently shown that in a smaller number of subjects, the magnitude of the increase in HRV peaked 2 to 7 days after smoking cessation and gradually declined thereafter. These 2 studies were not randomized trials. Therefore, there are some concerns about the time-related effect on the measures of HRV. Changes in body weight were not addressed, although smoking cessation is often associated with an increase in food intake and weight gain.¹⁷ Moreover, in the 2 previous studies, the daytime and nighttime values of the measures of HRV were not assessed separately, although it is of considerable interest to assess whether smoking cessation has an influence on the indices of HRV even in the nighttime when subjects do not smoke cigarettes. These factors may limit the interpretation of the data of the 2 earlier studies. The present study is the first conducted as a randomized crossover design with a considerable number of subjects, to elucidate the effects of smoking cessation on HRV.

The present results showed that the smoking cessation significantly decreased both the pNN50 and the HF component throughout a 24-hour period, indicating that in habitual smokers, parasympathetic nervous function is impaired even in the nighttime when they are sleeping and do not smoke cigarettes. As for the effect of smoking cessation on sympathetic activity in these subjects, plasma norepinephrine and epinephrine were lower in the nonsmoking period than in the smoking period, confirming previous observations.¹⁸ This finding is in line with the well-established view that smoking increases sympathetic outflow to the heart and some other vascular beds including peroneal muscle in humans.^{19 20 21} It has also been suggested that a smoking-associated impairment of the baroreflex ability to counteract peripheral adrenergic stimulation participates in the sympathoexcitatory effects of smoking in humans.^{22 23}

This is the first interventional and randomized trial to identify associations between smoking cessation and various cardiovascular indices, including ambulatory BP, HR, time domain, and frequency domain measures of HRV and plasma catecholamine levels. The present findings verified the substantial and immediate beneficial effects of smoking cessation on these cardiovascular indices. The clinical implications seem to be quite favorable even for individuals who have been long-term cigarette smokers.

	Acknowledgments

 
This work was supported by Kimura Memorial Heart Foundation Grant for Research on Sympathetic Nervous System and Hypertension (J.M.). We thank Nobuo Shirahashi, PhD, for assisting us in the statistical analysis.

Received September 15, 1998; first decision October 26, 1998; accepted November 9, 1998.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Minami, J. Articles by Matsuoka, H. Search for Related Content PubMed PubMed Citation Articles by Minami, J. Articles by Matsuoka, H. Pubmed/NCBI databases Medline Plus Health Information Quitting Smoking Smoking