One Way e-Cigarettes May Up CV Risk: Altering HR Variability

Larry Hand

February 01, 2017

LOS ANGELES, CA — Habitual e-cigarette use may increase the risk of cardiovascular disease by shifting the cardiac autonomic balance toward greater sympathetic activity and increasing oxidative stress, according to new research[1].

"The central message for cardiologists from our study is that habitual e-cigarette use is associated with altered heart-rate variability in the same pattern seen in tobacco cigarette smokers," Dr Holly R Middlekauff (David Geffen School of Medicine, University of California, Los Angeles) told heartwire from Medscape.

"This pattern of heart-rate variability has been associated with increased risk of myocardial infarction and sudden death in patients with heart disease, as well as in populations without known heart disease. Furthermore, habitual e-cigarette use is associated with increased susceptibility to oxidative stress, a critical component in the development of atherosclerosis," she said.

Middlekauff and colleagues conducted a study involving 23 self-identified otherwise-healthy e-cigarette smokers and 19 otherwise-healthy nonusers between 21 and 45 years old in 2015 and 2016.

Using electrocardiography and blood tests, they analyzed heart-rate variability by high-frequency component, which signals vagal activity, low-frequency component, which mixes vagal and sympathetic activity, and the ratio of low frequency to high frequency, which reflects the cardiac sympathovagal balance.

The researchers found the high-frequency component to be significantly decreased in e-cigarette users compared with nonusers (standard error of the mean [SEM], 46.5 nu vs 57.8 nu; P=0.04). They found the low frequency and the low–to–high-frequency ratio to be significantly increased (mean [SEM] 52.7 nu vs 39.9 nu; P=0.03; mean [SEM] 1.37 vs 0.85; P=0.05) in e-cigarette users, which they write as being consistent with sympathetic predominance.

They found plasma cotinine levels to be significantly related with each heart-rate variability components, inversely to high frequency (P =0.04) and directly to low frequency (P=0.03) and low–to–high-frequency ratio (P=0.03).

They also found LDL oxidizability to be significantly increased in 12 e-cigarette users compared with 18 nonusers (mean [SEM] 3801.0 U vs 2413.3 U; P=0.01). Paraoxonase-1 tended to be lower in e-cigarette users, which they write as being consistent with less protection against oxidative stress.

The researchers pointed out that both increased cardiac sympathetic activity and increased oxidative stress are known mechanisms of how tobacco smoking increases the risk of cardiovascular disease.

"We can conclude that habitual e-cigarette use is associated with physiologic effects. Nonetheless, we cannot confirm causality on the basis of this single, small study; further research into the potential adverse cardiovascular health effects of e-cigarettes is warranted," the researchers write in an article published online February 1, 2017 in JAMA Cardiology.

Middlekauff said cardiologists should be telling their patients, "E-cigarettes have real, physiologic, adverse effects. If you don't already smoke tobacco cigarettes, don't start using e-cigarettes. They are not harmless."

As for further research, she added, "We need to know whether the cardiac risks associated with e-cigarettes are as great as those associated with lethal tobacco cigarettes. We need to know which component of the e-cigarette aerosol is driving these adverse physiologic effects."

In an accompanying editorial[2], Dr Aruni Bhatnagar (University of Louisville, KY) writes that the nicotine in e-cigarettes "is a strong vasoactive drug that can profoundly affect cardiovascular function and health. . . . It has been shown that smoking e-cigarettes increases heart rate as well as diastolic and systolic blood pressure to levels comparable with those observed with conventional cigarettes."

He praised the researchers involved in the new study: "Such investigations are critical for evaluating how harmful e-cigarettes are and whether their widespread acceptance will decrease the incidence of cardiovascular disease or, by renormalizing smoking and promoting nicotine addiction, erode public-health gains made by evidence-based tobacco control and regulation."

Outside supporters of this research included the American Heart Association, the National Institute of Environmental and Health Sciences, and the Irma and Norman Switzer Dean's Leadership in Health and Science Scholarship program. The authors and editorialist reported no relevant financial relationships.

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