Smoking, Smoking Cessation and Risk of Sudden Cardiac Death in Women

Abstract

Background

Few prospective studies have examined quantitative cigarette consumption and smoking cessation on sudden cardiac death (SCD) risk among individuals without pre-existing coronary heart disease (CHD) with long-term follow-up.

Methods and Results

We prospectively examined the association between cigarette smoking and smoking cessation on the risk of SCD among 101,018 women participating in the Nurses’ Health Study without CHD, stroke and cancer at baseline 1980. During 30 years of follow-up, we identified 351 SCD events. Compared to never smokers, current smokers had a 2.46-fold (95% CI, 1.81–3.33) increased risk of SCD after controlling for coronary risk factors. In multivariable analyses, quantity of cigarettes smoked daily (P for trend, <.0001) and smoking duration (P for trend, <.0001) were linearly associated with SCD risk among current smokers. Small to moderate amounts of cigarette consumption (1–14 per day) were associated with a significant 1.86-fold (95% CI, 1.17–2.96) increase in SCD risk and every 5 years of continued smoking was associated with an 8% increase in SCD risk (HR 1.08; 95% CI, 1.05–1.12, p<.0001). The SCD risk linearly decreased over time after quitting and was equivalent to that of a never smoker after 20 years of cessation (p for trend <0.0001).

Conclusions

In this large prospective cohort of women without CHD at baseline, a strong dose response relationship between cigarette smoking and SCD risk was observed, and smoking cessation significantly reduced and eventually eliminated excess SCD risk. This suggests efforts to prevent SCD among women should include aggressive strategies for smoking cessation.

Introduction

Sudden cardiac death (SCD) is a leading cause of cardiovascular mortality.¹ Most SCDs occur in those without known cardiac disease and are not in the well recognized high risk subset with myocardial infarction (MI), impaired left ventricular ejection fraction (LVEF), and heart failure.^{2, 3} Therefore, the current paradigm for SCD prevention does not address the population with the highest number of SCD events. Understanding population-based characteristics that are associated with SCD risk is important for SCD prevention in the general population.

Cigarette smoking is strongly associated with SCD risk.^4–9 Although smoking status (current, past, never) is a well-established risk factor for SCD and coronary heart disease (CHD)^10–12, there are limited data on dose-response relationships between quantity of cigarettes smoked, smoking duration, as well as the impact of smoking cessation on SCD risk over a long follow-up. Data from prospective studies on dose-response relationships appear to conflict. ^{6, 11, 13} In the Framingham cohort¹³, quantity of cigarettes smoked daily was linearly associated with SCD risk only among men without underlying CHD, while a gradient in risk was not observed among patients with a prior history of CHD in the Bezafibrate infarction Prevention (BIP) Trial.¹¹ These studies were limited by relatively few numbers of SCD events, particularly among women. In addition, among patients with known CHD, smoking cessation has been associated with lower incidence of SCD;^{10–12, 14} however, sparse data exists regarding the benefits of smoking cessation among individuals without documented CHD, who comprise the majority of SCD events in the population.¹³

To better define the impact of smoking and cessation among women with and without CHD, we prospectively evaluated the association between amount of cigarette smoking (status, quantity of cigarettes smoked daily and duration of smoking) and smoking cessation on the risk of SCD among 101, 018 women free of cardiovascular disease at baseline in the Nurses’ Health Study over 30 years of follow- up.

Methods

The Nurses’ Health Study Cohort

The Nurses’ Health Study was established in 1976, consisting of 121 701 registered female nurses, 30 to 55 years of age who completed a questionnaire with detailed information about medical history, cardiovascular risk factors, menopausal status and lifestyle factors.¹⁵ Twice a year, follow-up questionnaires are mailed to update exposure information and ascertain newly diagnosed medical conditions.

Study Population

Follow-up for the present analysis began in 1980 to include important covariates (alcohol use, physical activity, and vitamin use), which were not ascertained until this follow-up period. Women who died prior to 1980 or with a missing date of death (n=748), had incomplete information regarding smoking questions (n=4118) or baseline characteristics (n=8634), and/or previous history of cardiovascular disease (CVD; angina, myocardial infarction (MI), coronary revascularization, or stroke) or cancer at baseline (n=7183) were excluded leaving 101 018 women who were included in the analysis. Women who reported coronary heart disease (angina, MI or coronary revascularization) during follow-up were not excluded from the primary analyses. This study was approved by the Partners Human Research Committee (Boston, Massachusetts) and subjects, or family members provided written, informed consent.

Assessment of Smoking

Participants reported whether they currently smoked or had ever smoked in the past and the age at which they started smoking on the initial questionnaire. Current smokers reported the number of cigarettes smoked per day. Past smokers reported the age at which they stopped smoking and the number of cigarettes smoked per day prior to quitting. At the start of each 2 year follow up cycle, women were reclassified according to most recent smoking status (never, past, current), quantity of cigarettes smoked per day, duration of smoking, and time since quitting among former smokers. We used cigarettes smoked per day and duration of smoking separately instead of a summary measure of pack-years which can classify women with varying doses and duration as having the same pack-years.¹⁶

End-Point Ascertainment and Definitions

The study end points included incident cases of SCD after the return of the 1980 questionnaire and before January 1, 2011. Deaths were reported by either next of kin, postal authorities or identified through a search of the National Death Index and confirmed with death certificates. We confirmed the endpoint of SCD through review of medical records, autopsy reports, and interviews with family members regarding the circumstances surrounding the death.

SCD classification has been previously described.⁶ Briefly, the etiology of cardiac death was considered sudden if the death or cardiac arrest precipitating death occurred within 1 hour of symptoms. Women with documented collapse of circulation (hypotension, exacerbation of congestive heart failure, or altered mental status) before disappearance of pulse were excluded from ‘arrhythmic deaths’ to increase specificity.¹⁷ Unwitnessed deaths occurring within 1 hour of symptom onset and with autopsy findings consistent with SCD were considered possible SCDs (n=31) and included in the analysis. In a secondary analysis, we included unwitnessed deaths and deaths that occurred during sleep where the women was documented to be asymptomatic in the preceding 24 hours and where circumstances suggested the death could be sudden (n=117). SCD events were confirmed by two Cardiologists.

Statistical Analysis

Person-years of follow up were calculated for each woman from date of return of the 1980 questionnaire to date of death or to January 1, 2011, whichever came first. Women with missing smoking data did not contribute person-time in the respective follow-up cycle. All other covariates with missing data had person-time assigned to a missing category for that covariate. In the present analysis, current smokers were classified into categories of cigarettes smoked per day; 1–14, 15–24 and ≥25. Current and past smokers were classified as ever smoker to assess duration of smoking which was classified into categories of years: ≤ 12, 13–≤24, 25–≤35 and >35. In addition, smoking duration was evaluated as a continuous variable in 5 year increments. For past smokers, cessation was classified into categories of years since quitting of <5, 5–<10, 10–<15, 15–<20 and ≥20. We used time-varying Cox models to estimate age and multivariable-adjusted hazard ratios for SCD across categories of smoking status, cigarettes smoked per day, smoking duration and years since quitting smoking. Never smoker was used as the reference group for analyses on smoking status, cigarettes smoked per day and smoking duration. Current smokers were used as the reference category for analyses examining smoking cessation among past smokers. All multivariable adjusted models included age, history of diabetes mellitus, hypertension, hypercholesterolemia, body mass index(<25, 25–29.9, ≥ 30 kg/m²), alcohol intake (0, 0.1–4.9,5.0–14.9,15.0–29.9, ≥ 30 g/d), physical activity (0,0–1.9,2–3.9, ≥ 4 hrs/wk), menopausal status and postmenopausal hormone use, usual aspirin use (<1, 1–5, ≥ 6 times/wk), multivitamin use, vitamin E use, and family history of MI (no, before age 60 y, after age 60 y).

A Wald test was conducted for linear trend by assigning median values to categories of cigarettes smoked per day, duration of smoking (years) and years since quitting and modeling this variable as a continuous variable. CHD was not controlled for in multivariable models because it is a potential intermediate on the causal pathway between smoking and SCD. In order to evaluate whether the association between smoking and smoking cessation differs once CHD becomes clinically manifest, a pre-specified analysis examining effect modification by history of CHD was performed. To test formally for an interaction between CHD and each smoking variable (status, quantity of daily cigarettes, duration and years since quitting), we added a cross-product term into separate multivariable models and used a likelihood ratio test, comparing a model with and without the interaction term. We then performed separate multivariable models stratified by CHD status prior to SCD.

Statistical analyses was performed by using of SAS software version 9.1.3 (SAS Institute Inc, Cary, North Carolina). All P values were two-sided and statistically significant at p ≤ 0.05.

Results

Among the 101 018 women free of CVD, stroke or cancer at baseline, 29.1% were current smokers, 26.4% past smokers and 44.5% never smokers. Women who reported current smoking were more likely to be postmenopausal and consumed ≥15.0 grams of alcohol per day. They were less likely to have a BMI ≥30 kg/m², regularly use multivitamin or vitamin E and participate in physical activity ≥ 4 hours/week compared to never smokers (Table 1).

Table 1.

Age-Standardized Characteristics by Smoking Status Among 101 018 Participants in the Nurses’ Health Study at Baseline in 1980.

Characteristic	Never (n=44904)	Past (n=26684)	Current (29430)
Smoking Status of participants (%)	44.5	26.4	29.1
Total person-years of follow-up	1 181 691	978504	396698
Duration of smoking, mean (SD), y	NA	14.7 (9.1)	26.6 (8.1)
Age at smoking initiation, mean (SD)	NA	15.6 (8.2)	18.1 (6.4)
Hypertension (%)	16	17	15
Diabetes (%)	2	2	2
High cholesterol (%)	5	6	5
BMI > 30 kg/m2 (%)	12	12	8
Parental MI at age ≤ 60 y (%)	11	13	13
Premenopausal (%)	61	61	56
Postmenopausal (%)	32	33	38
Current postmenopausal hormone use (%)	7	8	8
Aspirin Use 7+ times/week (%)	46	47	47
Multivitamin Use (%)	30	33	28
Vitamin E Use (%)	12	13	10
Alcohol Intake (%)
0.1 – 4.9 g/day	34	34	32
5.0 – 14.9 g/day	17	27	26
≥15.0 g/day	6	15	18
Physical Activity (hrs/wk) (%)
>0–1.9	34	33	37
2.0–3.9	25	23	28
≥ 4	41	45	34

^*All percentages are standardized for age to the total cohort. SD denotes standard deviations. BMI denotes body mass index

During 30 years of follow-up, there were 351 incident SCDs. Current smoking was associated with a 2.46-fold (95% CI, 1.81–3.33) increased risk of SCD compared to a never smoker in multivariable analysis (Table 2). In age and multivariable adjusted models, quantity of cigarettes smoked daily among current smokers was linearly associated with risk of SCD (Table 2, p for trend <.0001). Small to moderate amounts of daily cigarette consumption (1–14 per day) was significantly associated with a 1.86-fold (95% CI, 1.17–2.96) increase in SCD risk, and women who smoked 25 cigarettes or more had a 3.31 fold (95% CI, 2.05–5.35) increase in SCD risk compared to never smokers in multivariable models. Duration of smoking was also linearly associated with SCD risk (Table 3, p for trend <.0001), with the highest risk associated with a smoking duration greater than 35 years in both age and multivariable adjusted models (multivariable HR 2.23; 95% CI, 1.71–2.91). For every five years of continued smoking, there was an associated 8% increase in SCD risk (HR 1.08; 95% CI, 1.05–1.12, p<.0001) in multivariable analysis.

Table 2.

Age and Multivariable-Adjusted Relative Risks of SCD According to Smoking Status and Quantity of Cigarettes Smoked Daily for Current Smokers.

	Smoking Status			Quantity of Cigarettes Smoked Daily by Current Smokers
	Never (n=44904)	Past (n=26684)	Current (n=29430)	1–14 (n=8085)	15–24 (n=12630)	≥ 25 (n=8715)	P value for Trend
No. of events (n=351)	128	148	75	22	31	22
Person years of follow up (n=2 556 893)	1 181 691	978504	396698	142244	161000	93454
Incidence rate†	11	15	19	15	19	24
Age Adjusted	1.00 (referent)	1.32 (1.04–1.68)	2.42 (1.81–3.25)	1.69 (1.07–2.66)	2.65 (1.77–3.95)	3.70 (2.32–5.90)	<0.0001
Multivariable‡	1.00 (referent)	1.40 (1.10–1.78)	2.46 (1.81–3.33)	1.86 (1.17–2.96)	2.63 (1.74–3.96)	3.31 (2.05–5.35)	<0.0001

SCD indicates sudden cardiac death;

^*95% confidence intervals shown in parentheses.

^†Incidence per 100 000 person-years.

^‡Adjusted for age (continuous), diabetes (yes vs no), history of hypertension (yes vs no), hypercholesterolemia (yes vs no), body mass index (<25, 25–29.9, ≥ 30 kg/m²), alcohol intake (0, 0.1–4.9,5.0–14.9,15.0–29.9, ≥ 30 g/d), physical activity (0,0–1.9,2–3.9, ≥ 4 hrs/wk), menopausal and postmenopausal hormone use, usual aspirin use (<1, 1–6, ≥ 7 times/wk), multivitamin use (yes vs no), vitamin E use (yes vs no), and family history of MI (no, before age 60 y, after age 60 y)

Table 3.

Age and Multivariable-Adjusted Relative Risks of SCD According to Years of Smoking.

	Never (n=44904)	≤12 (n=1331)	13–≤24 (n=20832)	25–≤35 (n=17363)	>35 (n=4588)	P value for Trend
No. of events (n=351)	128	34	31	47	111
Person years of follow up (n=2 556 899)	1 181 565	323626	366063	344573	341072
Incidence rate†	11	11	8	14	33
Age Adjusted	1.00 (referent)	1.21 (0.83–1.77)	0.94 (0.63–1.39)	1.44 (1.03–2.02)	2.22 (1.71–2.87)	<0.0001
Multivariable‡	1.00 (referent)	1.35 (0.92–1.98)	1.02 (0.69–1.52)	1.47 (1.04–2.07)	2.23 (1.71–2.91)	<0.0001

SCD indicates sudden cardiac death; smoking duration includes ever smoke

^*95% confidence intervals shown in parentheses.

^†Incidence per 100 000 person-years.

^‡Adjusted for age (continuous), diabetes (yes vs no), history of hypertension (yes vs no), hypercholesterolemia (yes vs no), body mass index (<25, 25–29.9, ≥ 30 kg/m²), alcohol intake (0, 0.1–4.9,5.0–14.9,15.0–29.9, ≥ 30 g/d), physical activity (0,0–1.9,2–3.9, ≥ 4 hrs/wk), menopausal and postmenopausal hormone use, usual aspirin use (<1, 1–6, ≥ 7 times/wk), multivitamin use (yes vs no), vitamin E use (yes vs no), and family history of MI (no, before age 60 y, after age 60 y)

Women who quit smoking had a lower risk of SCD than women who continued to smoke (HR=0.57; 95% CI, 0.42–0.77), but their overall SCD risk remained elevated compared to women who never smoked (HR=1.40; 95% CI, 1.10–1.78) in multivariable analysis. Compared to current smokers, the hazard ratio for SCD linearly decreased among past smokers with length of time since quitting. (Figure 1, p<0.0001). This risk reduction became significant at > 15 years of smoking cessation, and by 20 years, the hazard ratio for SCD in comparison to women who continued to smoke was similar for past (HR=0.44; 95% CI, 0.31–0.64 and never smokers (HR 0.40,95% CI, 0.29–0.54).

Figure 1. Age and Multivariable Adjusted Hazard Ratios for SCD According to Years Since Quitting Among Past Smokers.

The error bars denote 95% confidence intervals. The reference category is current smokers. The white diamond represents age-adjusted HR. The black diamond represents multivariable HR adjusted for age, diabetes, history of hypertension, hypercholesterolemia, body mass index, alcohol intake, physical activity, menopausal and postmenopausal hormone use, usual aspirin use, multivitamin use, vitamin E use, and family history of MI. P value for trend, <0.0001 in the age and multivariable adjusted models.

In a secondary analysis, which included unwitnessed deaths where the women were documented to be asymptomatic in the 24 hours preceding death, the association between amount of cigarette smoking (quantity of cigarettes daily smoked and duration) and SCD risk were not materially altered. A linear association remained between quantity of cigarettes smoked daily (1–14: HR=1.76; 95% CI, 1.15–2.68), 15–24: HR 2.92;95% CI, 2.05–4.16, ≥25: HR=3.14;95% CI, 2.00–4.93, p for trend<0.0001) and duration of smoking (≤12: HR=1.34;95% CI, 0.96–1.88, 13–≤24: HR=1.08,95% CI, 0.76–1.52, 25–≤35: HR=1.33;95% CI, 0.97–1.82, >35: HR=2.42;95% CI, 1.93–3.04, p for trend<.0001) and SCD risk in multivariable analyses. Similarly, SCD risk reduction remained significantly associated with length of time since quitting (p<0.0001).

We then explored whether the association between smoking status and SCD differed by the presence or absence of established CHD (Table 4). Among women who did not develop clinically manifest CHD, the incidence rate of SCD was 10, 11 and 17 per 100,000 for never, past, and current smokers, respectively. For women who developed CHD, comparable rates were much higher (46, 83, and 78 per 100,000 for never, past, current smokers respectively). Overall, women with CHD who had quit smoking continued to have a higher SCD risk compared to never smokers (HR 1.87, 95% CI, 1.16–3.01); whereas women without CHD did not (p for interaction 0.15). SCD risk reduction associated with smoking cessation varied significantly among women with and without CHD (p for interaction=0.03). An immediate reduction in SCD risk at < 5 years was observed among women without CHD as compared to the more gradual risk reduction observed among women with CHD. The association between quantity of cigarettes smoked daily and duration of smoking and SCD did not significantly vary among women with and without CHD.

Table 4.

Multivariable-Adjusted Hazard Ratios of SCD According to Smoking Status, Quantity of Cigarettes, Duration and Smoking Cessation stratified by Clinically Apparent CHD at time of SCD.

	No CHD				CHD				P Value*
	No. of cases n=254	Person years of follow up n=2234289	IR†	Multivariable HR (95%)CI‡	No. of cases n=97	Person years of follow up n=144553	IR†	Multivariable HR (95%)CI‡
Smoking Status									0.15
Never	100	1035670	10	1.00 (Referent)	28	60371	46	1.00 (Referent)
Past	91	828023	11	1.17 (0.87–1.56)	57	68833	83	1.87 (1.16–3.01)
Current	63	370596	17	2.43 (1.72–3.42)	12	15349	78	1.81 (0.84–3.88)
No. Cigarettes Smoked (per category increase)									0.81
	63	370596	17	1.35 (1.21–1.51)	12	15349	78	1.32 (1.05–1.67)
Smoking Duration (per every 5 years)									0.70
	154	1198619	28	1.07 (1.03–1.11)	69	84182	161	1.09 (1.03–1.15)
Smoking Cessation (years)									0.03
Current	63	370596	17	1.00 (Referent)	12	15349	78	1.00 (Referent)
<5	10	114384	9	0.46 (0.24–0.91)	15	9174	164	2.14 (0.91–5.03)
5–<10	14	108069	13	0.63 (0.35–1.14)	9	9544	94	1.22 (0.48–3.11)
10–<15	9	107430	8	0.43 (0.21–0.87)	11	8492	130	1.59 (0.64–3.95)
15–<20	12	116613	9	0.51 (0.27–0.97)	5	8747	57	0.52 (0.17–1.61)
≥ 20	46	381526	12	0.44 (0.30–0.67)	16	32877	52	0.58 (0.25–1.34)
Never	100	1035670	9	0.41 (0.29–0.57)	26	60371	46	0.50 (0.23–1.08)

^*P for interaction

^†Incidence per 100 000 person-years.

^‡Multivariable models adjusted with updated values for age (continuous), diabetes (yes vs no), history of hypertension (yes vs no), hypercholesterolemia (yes vs no), body mass index (≥ 30 kg/m²), alcohol intake (≥ 30 g/d), physical activity (≥ 4 hrs/wk), menopausal and postmenopausal hormone use, usual aspirin use (≥ 7 times/wk), multivitamin use (yes vs no), vitamin E use (yes vs no), and family history of MI (no, before age 60 y, after age 60 y)

CHD defined as angina, MI or coronary revascularization

Discussion

In this large, long-term, prospective cohort of women free of CHD, stroke or cancer at baseline, quantity and duration of smoking was directly associated with SCD. In multivariable analysis, quantity of cigarettes smoked daily was linearly associated with SCD risk with almost a 2.5 fold increase associated with small to moderate amounts of cigarette consumption. With respect to smoking cessation, SCD risk reduction linearly increased with length of time since quitting, decreasing to the level of never smoker after 20 years. In stratified analyses, the elevated SCD risk associated with past smoking appeared to be limited to those with established CHD, and the time course of the SCD risk reduction associated with smoking cessation varied significantly among women with and without CHD. An immediate reduction in SCD risk was observed among women without CHD compared to the more gradual risk reduction observed among women with CHD.

These data regarding the association between smoking and SCD in women are generally consistent with those reported in other prospective population-based cohort studies. In a British study of 7735 middle-age men, current smoking was associated with SCD, but only in the absence of ischemic heart disease⁹. In the Framingham Study, smoking greater than 20 cigarettes per day was associated with a long-term elevation in SCD risk among women but not among men⁸. Smoking was not associated with an elevation in short-term risk in women or men. Earlier data from this cohort based on only 50 SCD events suggested a lack of a dose response relationship between cigarette smoking and SCD among women ¹⁸. Utilizing a total of 351 SCD events, we were able to demonstrate a strong dose response relationship between quantity of cigarettes smoked daily and SCD risk. Prior studies^{5, 18} also suggested that a gradient in SCD risk associated with increasing cigarette use was less apparent once CHD becomes clinically manifest, but we were able to demonstrate direct associations between number of cigarettes smoked among women with and without CHD.

Our data also reinforce the important concept that the SCD risk associated with cigarette smoking can be modified through smoking cessation. Smoking cessation has previously been associated with SCD risk reduction primarily in populations with established CHD^{10–12, 14}; whereas there is a paucity of data on smoking cessation and SCD among individuals without CHD. In the Framingham study, male smokers who were less than 65 at study entry and subsequently quit had half the sudden coronary death rate compared to those who continued to smoke over 18 years of follow-up.¹⁹ Similar to the above studies, we observed a reduction in SCD risk associated with smoking cessation in women. In contrast to prior data suggesting a fairly prompt reduction in SCD risk among patients with CHD^{10–12, 14}, our data suggests that SCD risk reduction may be more gradual once women develop manifestations of CHD. In this setting, severe and/or vulnerable coronary atherosclerotic plaques and resultant myocardial fibrosis and scarring may confer a residual SCD risk which persists for some time after smoking cessation. In contrast, the more immediate SCD risk reduction observed among women without CHD may, in part, be explained by alleviation of the more acute proarrhythmic effects of nicotine such as reductions in catecholamine release ¹⁹, alteration of potassium handling²⁰, and lowering of ventricular fibrillation threshold caused by transient enhanced platelet adhesion.¹⁹

This study has several strengths, including the prospective design, large number of participants with long follow-up, and outcome events confirmed by next-of-kin reports and medical record review. There are also several limitations of the present study which warrant discussion. First, information on cigarette smoking (status, quantity of cigarettes, duration, and years since quitting) was based on self-report, which could lead to misclassification. However, numerous validation studies have established the accuracy of self-reported smoking and other CHD risk factors in this cohort of health professionals^22–24. In addition, smoking characteristics were assessed on 2 year follow-up questionnaires and updated accordingly to further minimize misclassification. Second, determination of sudden death is difficult in free-living individuals and is susceptible to error. Accordingly, we tried to minimize error by employing a strict definition of SCD⁶ and requiring supporting information from medical records or witnessed reports. These strict criteria would have missed women who died suddenly without supporting information. However, our results were not significantly altered when a sensitivity analysis was performed which included a broader definition of SCD. Third, participants of the Nurses’ Health Study are predominately Caucasian (96%), relatively healthy and of a homogeneous socio-demographic status, and it is uncertain whether these results would be generalizable to other ethnicities and/or socio-demographic groups. Finally, due to the observational nature of the study, we cannot exclude the possibility that residual or unmeasured confounding may have accounted for part of the associations observed. However, given that the magnitude of observed associations were not altered after controlling for numerous CHD risk factors, substantial residual confounding is unlikely.

In summary, these prospective data provide further evidence that cigarette smoking is an important modifiable risk factor for SCD among women with and without CHD. A dose-dependent relationship between smoking and SCD was observed, and even small-to-moderate quantities of daily smoking were associated with SCD risk. Since SCD is often the first manifestation of CHD among women^{4, 6}, lifestyle modifications that reduce SCD in this apparently healthy subset of the population are particularly important. The benefits of smoking cessation on SCD risk in women are in keeping with benefits demonstrated for reductions in all-cause mortality, CHD and cancer.^{25, 26} Smoking cessation was associated with significant reductions in SCD risk in women both with and without CHD. The reduction in SCD risk may be more immediate among women without CHD arguing that efforts at smoking cessation should not await the development of CHD. Efforts to prevent SCD among women should consider aggressive strategies for smoking cessation among all women.