Objective: To determine whether exposure to secondhand smoke is associated with early prognosis following acute coronary syndrome.
Design, setting and participants: We interviewed consecutive patients admitted to nine Scottish hospitals over 23 months. Information was obtained, via questionnaire, on age, sex, smoking status, postcode of residence and admission serum cotinine concentration was measured. Follow-up data were obtained from routine hospital admission and death databases.
Results: Of the 5815 participants, 1261 were never-smokers. Within 30 days, 50 (4%) had died and 35 (3%) had a non-fatal myocardial infarction. All-cause deaths increased from 10 (2.1%) in those with cotinine ⩽0.1 ng/ml to 22 (7.5%) in those with cotinine >0.9 ng/ml (χ2 test for trend p<0.001). This persisted after adjustment for potential confounders (cotinine >0.9 ng/ml: adjusted OR 4.80, 95% CI 1.95 to 11.83, p = 0.003). The same dose response was observed for cardiovascular deaths and death or myocardial infarction.
Conclusions: Secondhand smoke exposure is associated with worse early prognosis following acute coronary syndrome. Non-smokers need to be protected from the harmful effects of secondhand smoke.
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Secondhand smoke (SHS) exposure predisposes to acute coronary syndrome (ACS) through a combination of mechanisms including endothelial dysfunction, platelet adhesion and plaque instability.1,2,3,4,5 SHS contains higher concentrations of toxins and small particles than mainstream smoke.6,7,8 Therefore, SHS exposure carries up to 90% of the risk of cardiovascular events associated with active smoking.1,9 Animal experiments suggest that SHS exposure may also result in larger infarctions and greater risk of ventricular hypertrophy.10,11 If so, SHS may impact adversely on prognosis; increasing the risk of recurrent events, heart failure and death.
Setting and participants
We previously conducted a before and after study evaluating the impact of the Scottish smoke-free legislation, which is reported in detail elsewhere.12 We used data from the patients recruited as part of the previous study to conduct this one. Data were collected prospectively on consecutive patients admitted with ACS to nine Scottish acute hospitals from May 2005 to March 2007 inclusive. ACS was defined as elevated cardiac troponin level following emergency admission for chest pain. To ensure complete case ascertainment, the hospital laboratories produced daily lists of troponin assays. Dedicated research nurses identified all eligible patients and conducted structured interviews that included self-classification of smoking status. Our study cohort comprised patients who classified themselves as never-smokers and did not have a serum cotinine concentration over 12 ng/ml. This is equivalent to a cut-off of 15 ng/ml for salivary cotinine, which is the standard criterion used to differentiate between active and non-smokers.13,14
Secondhand smoke exposure
Cotinine assays were performed on the clinical blood samples taken routinely on admission to hospital. All assays were performed in a single laboratory using gas chromatography with a specific nitrogen/phosphorus detector GC-NPD.15 Cotinine and the internal standard 5-methyl cotinine were extracted using dichloroethane from 100-μl samples after alkalisation using sodium hydroxide. The lower limit of detection was 0.1 ng/ml. Cotinine assays were used to provide an objective, quantitative measurement of recent, overall SHS exposure among non-smokers.13,16
The Information Services Division of NHS Scotland collates data routinely on all admissions to Scottish hospitals via the Scottish Morbidity Record (SMR) (http://www.isdscotland.org/isd/3348.html). The SMR records the date and urgency of admissions as well as the underlying clinical diagnoses. The General Registrar’s Office collates death certificate data for all deaths that occur in Scotland including date and cause of death (http://www.gro-scotland.gov.uk/statistics/deaths.html). Both databases use the International Classification of Diseases (ICD). Index cases were linked to the SMR and death certificate databases to provide follow-up information on fatal and non-fatal events. Patients who died before discharge from hospital were included in the analysis.
Quartiles (0.1 ng/ml, 0.3 ng/ml and 0.9 ng/ml) were used to categorise serum cotinine into four ordinal groups. Because a large number of participants had a cotinine concentration equivalent to the 25th percentile (0.1 ng/ml), the bottom two groups were unequal in size. Participants’ postcodes of residence were used to attribute Scottish Index of Multiple Deprivation (SIMD) scores (http://www.scotland.gov.uk/Topics/Statistics/SIMD/Overview). SIMD scores are an aggregated measure of material deprivation. They are derived from 37 indicators in seven domains (income, employment, health, education, access to services, housing and crime) and are determined at the data zone level (geographical areas with a median population of 769). SIMD scores were grouped into population quintiles. We defined three endpoints: all-cause death, cardiovascular death (ICD10 I00-I99) and a composite endpoint of all-cause death or readmission for a principal diagnosis of acute myocardial infarction (ICD10 I21 or I22). All were applied over the 30 days following the index admission. We examined the crude association between cotinine band and risk of each outcome using χ2 tests for trend and univariate logistic regression. We then adjusted for the potential confounders of age, sex and SIMD quintile in a multivariate logistic regression model. All analyses were performed using SPSS for Windows v13.0 software. The West Glasgow research ethics committee approved the study.
Between May 2005 and March 2007 inclusive, 6687 patients were admitted for ACS and 5815 (87%) consented to participate in the study. Of the 1408 patients who classified themselves as never-smokers, cotinine concentrations were both available and 12 ng/ml or less in 1261 (90%). These comprised the study cohort. Their geometric mean cotinine concentration was 0.382 ng/ml, their median age was 72 years (IQR 62–80) and 654 (52%) were male. Within 30 days of the index admission, 50 (4%) patients had died and a further 35 (3%) required readmission to hospital for myocardial infarction, giving a total of 85 (7%) adverse events. Overall, 132 (10.5%) never-smokers had a spouse or partner who smoked. The likelihood of a partner smoking increased significantly across the increasing cotinine bands from 10 (2.1%) patients with a serum cotinine concentration of 0.1 ng/ml or less to 93 (31.7%) patients with a cotinine above 0.9 ng/ml (χ2 test for trend, p<0.001)
There was a significant trend in the frequency of all-cause deaths by cotinine band from 10 (2.1%) deaths among patients with a serum cotinine concentration of 0.1 ng/ml or less, to 22 (7.5%) deaths among those with a cotinine level above 0.9 ng/ml (χ2 test for trend, p<0.001) (table 1). This trend persisted after adjustment for age, sex and SIMD quintile with a significantly higher risk among those with cotinine concentrations above 0.9 ng/ml (OR 4.80, 95% CI 1.95 to 11.83, p = 0.003) (table 2). The results were similar for cardiovascular death. In respect of the composite endpoint, there was also a significant trend in the frequency of total events from 23 (4.8%) among patients with a serum cotinine concentration of 0.1 ng/ml or less, to 29 (9.0%) deaths among those with a cotinine concentration above 0.9 ng/ml (χ2 test for trend, p = 0.014) (table 1). As before, this trend persisted after adjustment for age, sex and SIMD quintile with a higher risk among those with cotinine concentrations above 0.9 ng/ml (OR 2.42, 95% CI 1.28 to 4.59, p = 0.050) (table 2). Adjustment for troponin concentration did not attenuate the results with significant associations remaining for all-cause death (cotinine >0.9 ng/ml: adjusted OR 4.88, 95% CI 1.98 to 12.06, p = 0.003), cardiovascular death (cotinine >0.9 ng/ml: adjusted OR 4.84, 95% CI 1.82 to 12.92, p = 0.012) and death or myocardial infarction (cotinine >0.9 ng/ml: adjusted OR 2.43, 95% CI 1.28 to 4.60, p = 0.050).
Among the 1831 current smokers excluded from the primary analyses, 53 (3%) died and 78 (4%) died or were readmitted for myocardial infarction within 30 days of the index admission. The early risk of death in smokers was comparable to that among never-smokers with cotinine concentrations below the median and significantly less than that in never-smokers as a whole (univariate OR 0.60, 95% CI 0.41 to 0.88, p = 0.008). However, the difference was no longer statistically significant when adjusted for differences in age. Similarly, smokers had a lower risk of total events on univariate analysis (OR 0.61, 95% CI 0.46 to 0.83, p = 0.001) but not after adjustment for age.
Among never-smokers admitted for ACS, there was a dose-response effect whereby increasing levels of SHS exposure were associated with increasing risk of early adverse events. SHS exposure is known to increase the risk of developing atherosclerosis. Side-stream smoke contains higher concentrations of toxic gases and small, respirable particles than mainstream smoke.5 It rapidly induces platelet aggregation, thrombosis, endothelial dysfunction, increased arterial stiffness and inflammation.1,2,3,4,5 Even brief exposure can produce changes in endothelium-dependent vasodilation17 and platelet activation of a comparable magnitude to those observed in active smokers.18
SHS exposure is also associated with disease progression. In a population cohort, those exposed to SHS had 20% higher progression of carotid intima media thickness over three years.19 In the apoE-deficient murine model, exposure to SHS for 21 days increased atherosclerotic lesions by 76%.19 In a case-control study of non-smokers married to smokers, there was a dose-response relation between the number of arteries stenosed and SHS exposure measured by the number of cigarettes smoked by partners and their duration of smoking.20 In contrast, there is a paucity of data on whether SHS exposure affects prognosis following ACS. The only previous study comprised 2172 patients admitted for either myocardial infarction or unstable angina.21 They included both smokers and non-smokers. SHS exposure was recorded as a self-reported binary variable (yes/no). Overall, 46% of participants reported SHS exposure and follow-up information was available on 1683 (77%). Those exposed to SHS had a higher risk of adverse events (death or rehospitalisation) within 30 days (adjusted RR 1.61, 95% CI 1.14 to 2.8). There was a dose response in relation to the number of years index cases had lived with their smoking partner. In a subgroup analysis of non-smokers, exposure to SHS carried a relative risk of recurrent events of 1.37 (95% CI 1.11 to 1.61).
Our study design has a number of strengths. Our cohort is restricted to one clinical presentation of cardiovascular disease and cases were recruited prospectively using one standard case definition that incorporated biochemical confirmation. Panagiotakis et al validated self-reported SHS exposure against the reports from relatives but did not have access to biochemical measurements.21 We had cotinine concentrations providing confirmation of smoking status and an objective measurement of recent exposure to SHS. Also, a quantitative measurement of SHS exposure enabled us to examine whether there was evidence of a dose response. Panagiotakis et al achieved 77% follow-up.21 In Scotland we are fortunate to have very complete and accurate routine data systems. Linkage to such data has been shown to be as complete as the prospective follow-up achieved in large clinical trials.22
The effect of SHS exposure on prognosis following ACS may be mediated via ongoing exposure after the incident event. For example, non-smokers married to smoking partners are likely to continue to be exposed. Alternatively, it may reflect a more severe initial presentation among those exposed to SHS before the event. Panagiotakos et al reported a correlation between years of exposure to SHS and both troponin I and creatine kinase concentrations.21 Non-smokers presenting with Q-wave myocardial infarction reported longer exposure to SHS than those presenting with non-Q-wave myocardial infarction or unstable angina.21 Animal models have demonstrated associations between SHS exposure and both infarct size11 and left ventricular hypertrophy,7 with evidence of a dose response in the former.11 People exposed to SHS for two hours in an airport smoking lounge experienced a reversible 12% reduction in heart rate variability.23 This magnitude of change can increase the risk of ventricular fibrillation or tachycardia following ACS.1
Future studies are required to determine whether the effect is mediated via the initial infarct or ongoing exposure, to examine other outcomes such as heart failure, and to determine whether the worse prognosis is sustained over the longer term.
We are grateful to the research nurses who collected the baseline data: Judith Anderson, Anne Andrews, Sharon Cameron, Jackie Dougall, Carole Gibson, Joanne Kelly, John Rodgers, Karen Smith, Fiona Stevenson, Helen Waldie, Ann Wright, Jim Young, and to the Clinical Biochemists who provided access to the clinical samples: James Burns, Ann Cruikshank, Callum Fraser, Jacqueline McGuire, Elliott Simpson, Peter Stromberg and Simon Walker. We are grateful to the Wellcome Trust Clinical Research Facility in Edinburgh and the ABS Laboratory in London.
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