1. Introduction
Smoking is the leading cause of preventable premature mortality in the world. Death is mainly caused by ischemic heart disease, stroke, lung cancer, and the catastrophic complications of advanced stage chronic obstructive pulmonary disease [
1]. It has been estimated that the 10-year fatal cardiovascular risk is doubled in smokers [
2], and that for young smokers the risk for myocardial infarction is up to 5-fold higher compared to non-smokers [
2,
3]. The risk is primarily related to the amount of tobacco smoked daily and shows a clear dose-response relationship with no obvious lower limit for deleterious effects [
4,
5]. By sustaining low-grade systemic inflammation [
6] and contributing to arterial stiffness [
7], tobacco smoke is also likely to lead to arterial hypertension [
8], thus further worsening smokers’ cardiovascular risk profile.
The interaction between smoking and blood pressure (BP) is complex. Despite the strong relationship between smoking and elevated risk for cardiovascular disease [
9,
10], there is paucity and discrepancy about the long-term effects of smoking cessation on BP in already established hypertension [
11,
12,
13].
Electronic cigarettes (ECs) are battery-operated devices designed to vaporise nicotine without burning tobacco. These consumer products share many similarities with smoking in the behavioural aspect of their use [
14]. Users are predominantly smokers, who report using them long-term as an alternative for conventional cigarettes, to reduce cigarette consumption or quit smoking, to relieve tobacco withdrawal symptoms, and to continue having a “smoking” experience [
15], but with much reduced health risks [
16,
17].
Data from clinical trials of “healthy” smokers [
18,
19,
20] and in vulnerable populations [
21,
22] have shown that ECs may help smokers with quitting or reducing their tobacco consumption and their use is well tolerated. There is no data about changes in smoking behaviour after daily ECs use among smokers with arterial hypertension. Most importantly, it is unknown if long-term smoking cessation/reduction after switching to regular “vaping” (the act of inhaling vapour from ECs) in patients taking anti-hypertensive medications could result in improved resting BP and better BP control.
Here we report, for the first time, long-term improvement in resting BP as well as in level of BP control in smokers with a diagnosis of hypertension who quit or reduced substantially their tobacco consumption by switching to ECs.
4. Discussion
Smoking is known to act synergistically to elevate the risk of myocardial infarction in patients with established hypertension [
25]. Moreover, there is emerging evidence that arterial hypertension may be one of the many recognized deleterious effects of tobacco smoking [
26]. For these reasons, quitting smoking is among the most important steps patients with elevated BP can take to improve their cardiovascular health [
5]. Abstinence has been the preferred strategy to address these harmful effects, but has been largely unsuccessful with modest quit rates being reported [
27,
28].
Here we illustrate for the first time the utility of ECs as a bridge in reducing cigarette consumption in smokers with arterial hypertension. Adoption of regular long-term ECs use in this group led to a marked and stable reduction in conventional cigarette consumption, with about 50% of them abstaining completely from tobacco smoking by the end of the observation period. The success rate observed in these patients with arterial hypertension is similar to that recently reported in asthmatics [
22] and may be explained by the notion that ECs are a valid long-term alternative nicotine source to conventional cigarettes due to their many similarities to smoking behaviour [
14,
29]. Moreover, ECs use was well tolerated with no reported severe adverse reactions or acute decompensation in BP.
As a result of the substantial reduction in cigarette consumption, decreased systolic and diastolic BP as well as improved BP control was also reported. In the EC group, systolic and diastolic BP fell by 10 mmHg and 6 mmHg, respectively. Improvement in systolic (but not diastolic) BP was also observed in dual users at 12 (but not 6) months. These findings are in agreement with the 8.8 mmHg reduction in systolic BP at week-52 in a prospective randomised control trial looking at the effect of smoking cessation by using ECs in subjects with high BP at baseline [
30]. Predictably, not only was there a decrease in the proportion of patients with hypertension, but also the overall proportion of patients in the EC group with good BP control increased five-fold compared to the reference group. Of note, improvement in resting BP as well as in level of BP control was unrelated to the minor adjustments in the use of anti-hypertensives.
Given the well-established acute effect of smoking on immediate vasopressor and tachycardic responses [
31,
32] and increased arterial stiffness [
33], the observed reduction in BP after long-lasting smoking reduction or abstinence is not surprising. Nonetheless, in view of the complex interaction between smoking and blood pressure (BP) and the reported discrepancy about the long-term effects of smoking cessation on BP in already established hypertension [
11,
12,
13], our positive findings require explanation. Besides important methodological limitations of population studies that may predispose them to heterogeneous results [
26], the association of elevated risk for future development of hypertension after smoking cessation [
13] has been mainly attributed to post-cessation weight gain [
8,
34]. Low BP in smokers is related to decreased body weight [
35] with higher body weight and elevated BP being more common in former smokers compared to non-smokers [
36]. Thus, when interpreting BP variations in the context of smoking abstinence, post cessation weight gain becomes a critical confounder because the negative effects of weight gain on BP could outweigh the positive effects of smoking cessation. In the current study, we have observed that quitters who use ECs seem to limit substantially their post-cessation weight gain; a significant but small, increase in body weight (i.e., 1.2 kg) was observed at the second follow-up visit, but the observed small weight gain was not significant between EC group and reference group (1.2 kg vs. 0.7 kg). The trivial post-cessation weight gain after switching to regular EC use might have contributed to the positive long-term effects of smoking cessation on BP and BP control. Moreover, improved weight control has been shown in a recent one-year randomized smoking cessation trial of smokers who quit smoking by switching to ECs [
37]. By alleviating weight gain, EC use may ultimately deter the hypertensive comorbidities of both smoking and obesity. Additionally, it must be noted that we investigated a relatively “young” population with a short duration of hypertension history and probably less established vascular remodelling; this might also have contributed to the positive effects on BP and BP control.
In agreement with the findings from other research groups [
38,
39], positive improvements in BP after smoking cessation were noted not only in quitters, but also in those who reduced consumption in conventional cigarettes (i.e., dual users). A possible explanation is that dual users in our study substantially reduced their average cigarettes/day consumption, with 77.3% reporting a reduction of at least 75% from baseline by the end of the observation period. Of note, that reduction in tobacco smoking thanks to ECs may have led to improvements in BP which is also consistent with the results of a recent prospective RCT [
30]. The multiple linear regression model in which the SBP change from BL to week 52 was entered as a dependent variable and tested against continuous smoking phenotype classification, sex, age, and weight change as independent variables, demonstrated that the mean reduction in systolic BP from baseline at one-year remained significantly associated with both smoking reduction and smoking abstinence, with the b coefficient for quitters being more than two-fold greater compared to reducers.
The observed improvement in systolic and diastolic BP as well as in BP control in hypertensive smokers who switched to regular ECs use suggests that the harmful effects of cigarette smoke on the vascular system can potentially be reversed. By substantially reducing exposure to conventional cigarettes’ hazardous toxicants and achieving clinically relevant BP reductions, EC use may not only improve the cardiovascular risk profile but also confer an overall health advantage in smokers unable or unwilling to quit who are also at risk of developing arterial hypertension compared to continuing smoking. The use of low risk nicotine-containing products (including ECs) should be investigated as a safer alternative approach to harm-reversal (i.e., specific reversal of BP elevation) and, in general, to harm-reduction (i.e., overall reduction of cardiovascular risk associated with tobacco smoking).
There are some limitations in our study. First, the sample size is small; hence the results must be interpreted with caution. However, despite being small, significant results were reported for several study endpoints. Standard concerns associated with retrospective studies (including variance in the quality of information recorded by medical professionals and difficulty in establishing a causal relationship) need consideration. Nonetheless, a clear advantage conducting this type of study is the generation of hypotheses that can be tested prospectively under controlled conditions. Secondly, patients in this study may represent a self-selected sample, which is not representative of all smokers with arterial hypertension (e.g., smokers not intending to quit, switching to ECs). Thirdly, although careful extraction from patients’ medical records allowed systematic assessment of anti-hypertensive medication prescriptions, this alone may not reflect true usage due to lack of rigorous adherence checks. Carbon monoxide measurements are not routinely performed in patients who are followed-up for elevated blood pressure at outpatient clinics and their smoking abstinence was self-reported. However, self-reported number of cigarettes smoked per day in studies of this type is not subjected to the kind of biases observed in clinical trials where there is the tendency to claim abstinence [
40]. Moreover, similar beneficial effects were also reported in dual users (i.e., smoking reducers) and therefore objective measures of abstinence are unlikely to be of great importance. Given the design of this study, it was impossible to provide details about specific products and patterns of use, but this (lack of) knowledge will not change study findings or their interpretation. Last but not least, lifestyle changes (e.g., salt intake, diet, recreational exercise), which may have an influence on BP measures, were not taken into account. Nonetheless, by including a reference group, which was carefully matched for age, sex, weight, and systolic BP fluctuations between pre-baseline and baseline visits, we minimized the observation bias.
