Smoking-associated electrocardiographic abnormalities predict cardiovascular mortality

Abstract

Background -Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. In electrocardiogram (ECG) recordings abnormal durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality. Previous analyses of the National Health and Nutrition Examination Survey (NHANES) database for associations between smoking and ECG abnormalities were incomplete. To elucidate how smoking affects cardiac excitation, we assessed in a nationally representative sample (NHANES III) the association between serum cotinine and P duration, PR interval, PR segment, rate-corrected QT (QTc), QRS duration, and JT interval. Methods and Results-We analyzed data from 5,653 adults using survey-weighted multinomial logistic regression to estimate associations between tobacco use (> 15 ng/ml serum cotinine) and short (< 5th percentile) or long (> 95th percentile) ECG intervals, relative to reference (5-95th percentile). After adjustment for demographics, risk factors, and conduction-altering medications, smoking was associated with a higher odds of short PR interval, PR segment, and QRS, and long JT. Broader effects of smoking on ECG were also assessed by survey-weighted linear regression of continuous cotinine and ECG, which revealed cotinine inversely associated with PR segment and QTc. Over a 22-year follow-up, many ECG abnormalities predicted cardiovascular mortality in smokers, including long JT, QRS, and QTc, and short QRS, whereas only short JT predicted mortality in nonsmokers. Conclusions -Smoking increases likelihood for rapid atrioventricular and ventricular depolarization and slow ventricular repolarization, which may promote cardiac arrhythmia and mortality.

Keywords: Cigarette; Cotinine; Electrocardiography; JT interval; P wave; PR interval; PR segment; QRS duration; QT interval; Smoking.

Fig. 1

Association of ECG abnormalities with smoking status. Association of ECG abnormalities with smoking status. Forest plots of hazard ratios (± 95% confidence intervals) among smokers for abnormal durations in ECG intervals and their components. ECG variables groups: Short (< 5th percentile), reference (5-95th percentile) and Long (> 95th percentile). Models adjusted as detailed in Methods for demographics (Model 1), plus cardiovascular risk factors (Model 2), plus medications (Model 3). Model 4 was adjusted only for baseline variables associated with specific ECG parameters in this study population, including PR interval (age, sex, previous cardiovascular disease, beta blockers, calcium channel blockers, heart rate), P duration (age, sex, race-ethnicity, congestive heart failure, alcohol intake, beta blockers, calcium channel blockers, heart rate), PR segment (age, sex, alcohol intake, calcium channel blockers, heart rate), QTc interval (age, chronic obstructive pulmonary disease, beta blockers, calcium channel blockers), QRS duration (sex, obese, chronic obstructive pulmonary disease, heart rate), and uncorrected JT interval (age, sex, dyslipidemia, alcohol intake, heart rate, anti-arrhythmic drugs).

Fig. 2

Concentration-dependent relationship between serum cotinine and shortening of PR segment or QTc. A, linear relationships of PR segment (ms) and QTc interval (ms) with cotinine levels. B, representation of progressive shortening of PR segment and QTc with corresponding increases in serum cotinine.

Fig. 3

Risk of long-term mortality among smokers and nonsmokers with prior ECG abnormalities. Forest plots of hazard ratios (± 95% confidence intervals) for ECG categories and mortality in smokers (green diamonds) and non-smokers (blue squares). Models adjusted for demographic variables, cardiovascular risk factors, heart rate (omitted for QTc), and select medications using covariates for Model 3 detailed in Fig. 1.

Fig. 4

Associations of ECG abnormalities and cardiovascular mortality among smokers and non-smokers. Kaplan-Meier survival estimates for cardiovascular disease-attributable mortality stratified by smoking status and ECG abnormality at time of exam. Time is indicated as months from exam.

Fig. 5

Summary of ECG abnormalities associated with smoking status.