Date Published: April 9, 2019
Publisher: Public Library of Science
Author(s): Federico Murgia, Roberto Melotti, Luisa Foco, Martin Gögele, Viviana Meraviglia, Benedetta Motta, Alexander Steger, Michael Toifl, Daniel Sinnecker, Alexander Müller, Giampiero Merati, Georg Schmidt, Alessandra Rossini, Peter P. Pramstaller, Cristian Pattaro, Katriina Aalto-Setala.
Heart rate variability (HRV) reflects the autonomous nervous system modulation on heart rate and is associated with several pathologies, including cardiac mortality. While mechanistic studies show that smoking is associated with lower HRV, population-based studies present conflicting results.
We assessed the mutual effects of active smoking status, cumulative smoking history, and current smoking intensity, on HRV among 4751 adults from the Cooperative Health Research In South Tyrol (CHRIS) study. The HRV metrics standard deviation of normal-to-normal (NN) inter-beat intervals (SDNN), square root of the mean squared differences of consecutive NN intervals (RMSSD), total power (TP), low (LF) and high frequency (HF) power, and their ratio (LF/HF), were derived from 20-minute electrocardiograms. Smoking status, pack-years (PY), and tobacco grams/day from standardized questionnaires were the main exposures. We fitted linear mixed models to account for relatedness, non-linearity, and moderating effects, and including fractional polynomials.
Past smokers had higher HRV levels than never smokers, independently of PY. The association of HRV with current smoking became apparent when accounting for the interaction between smoking status and PY. In current smokers, but not in past smokers, we observed HRV reductions between 2.0% (SDNN) and 4.9% (TP) every 5 PY increase. Furthermore, current smokers were characterized by dose-response reductions of 9.8% (SDNN), 8.9% (RMSSD), 20.1% (TP), 17.7% (LF), and 19.1% (HF), respectively, every 10 grams/day of smoked tobacco, independently of common cardiometabolic conditions and HRV-modifying drugs. The LF/HF ratio was not associated with smoking status, history, or intensity.
Smoking cessation was associated with higher HRV levels. In current smokers, heavier smoking intensity appears gradually detrimental on HRV, corroborating previous evidence. By affecting both the sympathetic and parasympathetic nervous system indexes, but not the LF/HF balance, smoking intensity seems to exert a systemic dysautonomic effect.
Heart rate variability (HRV) is defined as the temporal variation between consecutive heartbeat intervals . It mainly reflects the dynamic and adaptive modulation of the rhythmicity of the sinoatrial node by stimuli from the autonomous nervous system (ANS). The HRV is usually estimated through metrics extracted from electrocardiogram (ECG) traces. Such metrics reflect time and frequency domains of the heart activity  and return complementary information on the parasympathetic activity and on the sympathetic/parasympathetic balance of the ANS .
Participants had a mean age of 46.2 years (range 18–93), with the youngest age observed for current smokers (Table 1), and 55.4% were women. Subjects with hypertension, history of cardiovascular events, and diabetes were 29.0%, 8.9%, and 4.6%, respectively. The study sample included 52.2% never smokers, 29.7% past smokers, and 18.1% current smokers. The mean age at smoking onset was 17.1 years (standard deviation, SD = 3.9), with minimal difference between past (mean = 16.9, SD = 4.3) and current (mean = 17.2, SD = 3.7) smokers. The median smoking duration was 11.0 (interquartile range, IQR: 8.0, 20.0) and 16.5 (IQR: 7.0, 22.3) years for past and current smokers, respectively. Among ever smokers, current and past smokers had smoked a median of 11.2 (IQR: 4.5, 22.0) and 8.5 (IQR: 3.3, 8.5) pack-years, respectively. Among current smokers, the median smoking intensity was 10.0 (IQR: 6.0, 18.0) grams a day. Participants’ characteristics by smoking status are described in Table 1.
In this study, we assessed the effects of multiple dimensions of smoking (i.e. smoking status, cumulative smoking history, and smoking intensity) on cardiac autonomic function using HRV metrics in a large general adult population sample. Our results indicate that HRV is strongly associated with smoking intensity, evaluated as grams of tobacco a day, in current smokers. Current smokers exhibited a decaying pattern of HRV level by more than 9% every 10 grams of daily smoked tobacco. Results were confirmed by metrics derived in terms of both time and frequency domains of HRV. Consequently, if smoking intensity is not accounted for, classical smoking status classification among never, past, and current tobacco users, may not entirely reflect the peculiar association with HRV. In our structured analytical framework, the effect due to smoking status became interpretable when we first included pack-years in the model and next, even more so, by the alternative inclusion of current smoking intensity. Further, smoking status and intensity were associated with HRV independently of the most common cardiometabolic conditions, including use of medications that potentially alter HRV levels, suggesting current progressively heavier smoking as an independent risk factor for lower HRV levels. Past smokers exhibited higher levels of HRV than never smokers. This effect was not entirely offset by lower HRV levels per increasing numbers of pack-years.
In conclusion, current smoking intensity is associated with a steep HRV reduction, as highlighted by both time and frequency domain indexes. Different components of smoking behavior may affect HRV in different ways. Sole inclusion of any single component may lead to erroneous conclusions. We warrant longitudinal studies to adopt our comprehensive modelling strategy, encompassing active smoking status, history, and intensity, with possible extension to passive smoking exposure, to illuminate further the smoking-HRV relationship on a temporal scale.