Association of household secondhand smoke exposure and mortality risk in patients with heart failure

NHANES III is cross-sectional survey in a nationwide probability sample of non-institutionalized civilian resident population in the United States. It is designed to assess the health and nutritional status of adults and children in the United States. From 1988 to 1994, 33,994 sample participants were interviewed and 30,818 participants were examined. Detailed descriptions of plan and operation of NHANES III is available on the website of National Center for Health Statistics [13]. The study was approved by the National Center for Health Statistics Research Ethics Review Board, and a signed informed consent form was obtained from every participant. Our study included currently nonsmoking adults (≥18 years) with a self-reported history of heart failure from survey participation. Participants with a history of non-skin cancer were excluded because of poor prognosis. There were totally 19,592 adults in NHANES III. Among them, 18,810 denied a history of heart failure, and 28 had no idea about their heart failure history. There were 757 participants with a history of heart failure in NHANES III. Among them, 126 current smokers and 59 participants with a history of non-skin cancer were excluded. Finally, 572 heart failure patients were included in the analysis.

Data on household SHS exposure were obtained from the Family Characteristics section of the interview. The specific question was “Does anyone who lives here smoke cigarettes?” If the answer was yes, the participant was considered to be exposed to household SHS.

Data on mortality status of included participants were obtained from the 2011 Public-Use Mortality Linked File. The file provided mortality follow-up data from the date of survey participation through December 31, 2011. Identifier data were matched to the National Death Index using a probabilistic matching algorithm. A detailed description of the linkage methodology has been published [14].

The primary analytic goal was to assess the association of household SHS exposure and mortality risk in patients with heart failure.

Continuous variables were expressed as mean ± SD, and categorical variables were expressed as percentage. The differences between groups were tested by t test and Pearson’s chi-squared test, respectively.

We calculated unadjusted rates of death per person-year. Kaplan-Meier survival curves and log-rank test were used to evaluate the mortality risk of SHS exposed and unexposed group. We used univariate Cox proportional-hazards models to assess the association of household SHS exposure and mortality risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Follow-up began at the time of interview and ended on the date of death or December 31, 2011, whichever came first. We then used multivariate models to adjust for potential confounders. Model 1 included age, gender, race, education level, family income, urbanization classification of the county, medication, and NHANES III phase. Model 2 included variables in model 1, self-reported general health status, and comorbidities (hypertension, diabetes, hypercholesterolemia, myocardial infarction, chronic kidney disease, COPD/emphysema). Model 3 included variables in model 2, physical functioning, heart rate, systolic, and diastolic blood pressure. However, analysis of Model 3 was exploratory because physical functioning, blood pressure, and heart rate are probably in the causal pathway between SHS exposure and mortality among patients with heart failure. Subgroup analyses were performed among ex-smokers (those who had smoked at least 100 cigarettes) and never-smokers (those who hadn’t smoked 100 cigarettes). A sensitivity analysis was performed by excluding those who died within 6 months. We imputed missing values of covariates using multiple imputation with a Markov Chain Monte Carlo method. Variables listed in Table 1 were included in the imputation model. The assumption of proportional hazards was confirmed for all variables.

Baseline characteristics were summarized in Table 1. Eighty-eight patients were exposed to household SHS, and 484 were not. Exposed patients were younger than the unexposed. Patients with household SHS exposure were more likely to be non-Hispanic Black, have a family income of more than 20,000 dollars, and have a larger household size, while those without exposure were more likely to live in an urbanized area, take beta-blockers, and have a history of myocardial infarction. The mean diastolic blood pressure in exposed group was 3.5 mmHg higher than that in unexposed group. Other baseline characteristics were comparable in both groups.

During a mean follow-up period of 9.2 years, there were 475 deaths (72 deaths in exposed group and 403 deaths in unexposed group). Rates of death per person-year were comparable between two groups (88.0 and 90.4 deaths per 1000 person-years in exposed group and unexposed group, respectively) (Table 2). Kaplan-Meier survival curves showed similar results (P for log-rank test = 0.864) (Fig. 1). Results of Cox regression models were summarized in Table 3. In the univariate analysis, household SHS exposure was not associated an increased mortality risk (HR: 0.98, 95% CI: 0.76–1.26, p = 0.854). However, after adjusting for demographic variables, socioeconomic variables, and medication in Model 1, household SHS exposure was associated of a 43% increase of mortality risk (HR: 1.43, 95% CI: 1.10–1.86, p = 0.007). Model 2 further adjusted for self-reported general health status and baseline comorbidities, and HR for the association was 1.47 (95% CI: 1.13–1.92, p = 0.005). Result in Model 3 was consistent. In subgroup analyses, the associations of household SHS and mortality risk did not differ significantly between ex-smokers and never-smokers (p for interaction> 0.1). Excluding death within 6 months did not significantly change the results (HR: 1.38, 95% CI: 1.05–1.82, p = 0.020 for Model 1; HR: 1.42, 95% CI: 1.08–1.88, p = 0.014 for Model 2; HR: 1.35, 95% CI: 1.02–1.80, p = 0.037).