Cigarette Smoking, Smoking Cessation, and Heart Failure Subtypes: Insights From the Jackson Heart Study

Abstract

Background

Cigarette smoking has been associated with incident heart failure (HF). However, the association between cigarette smoking and smoking cessation with HF subtypes has not been well elucidated, particularly among Black people.

Methods and Results

We investigated 4189 (never smoker n=2934, former smoker n=761, current smoker n=464) Black participants (mean age 54 years, 64% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the association of cigarette smoking with incident HF hospitalization and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction). After adjustment for confounding factors, current smoking was associated with incident HF (both subtypes) compared with never smoking. Smoking intensity among those who identified as currently smoking and smoking burden among those who ever smoked were associated with higher incidence of HF with preserved ejection fraction compared with never smoking. Lung function evaluated by spirometry at baseline did not significantly influence these associations. The risk of developing HF decreased with more years after smoking cessation, and more than 20 years of smoking cessation were required to reach a risk comparable to that of never smoking.

Conclusions

Smoking cigarettes was associated with developing both subtypes of HF and it was independent from the influences on baseline lung function. Long‐term smoking cessation is necessary to prevent the onset of HF in people who smoke cigarettes.

Nonstandard Abbreviations and Acronyms

HFpEF

heart failure with preserved ejection fraction

HFrEF

heart failure with reduced ejection fraction

JHS

Jackson Heart Study

Clinical Perspective.

What Is New?

In our large community‐based cohort of Black adults, current smoking was associated with both incident heart failure (HF) with reduced ejection fraction and HF with preserved ejection fraction hospitalizations, independent of the effects of smoking on lung function.

It took ≈20 or more years of cigarette smoking cessation to reduce the risk of developing HF in former smoking to similar risk of never smoking.

What Are the Clinical Implications?

Given the higher rates of HF and worse outcomes in Black people with HF, smoking cessation and prevention of smoking should be targeted and promoted better in Black people.

During the past 3 decades, the prevalence of heart failure (HF) has been increasing, particularly HF with preserved left ventricular ejection fraction (HFpEF). ¹ The number of patients with HF is expected to exceed 8 million in the United States by 2030, and the social and economic burden is enormous. ² The pathophysiology of HFpEF is heterogeneous and development of effective therapeutic strategies has been challenging. ³ , ⁴ Therefore, investigating risk factors for the development of HFpEF to inform preventive strategies is quite important.

We have previously reported that cigarette smoking is associated with incident HF among Black adults after adjusting for possible confounding factors and incident coronary heart disease (CHD), and several other studies suggest the influences of cigarette smoking on incident HF. ⁵ , ⁶ , ⁷ However, less is known about the effects of smoking and risk of HF subtypes. Abnormal respiratory function and right HF may play a role and mediate the relationship between cigarette smoking and HFpEF, but this has not been adequately studied. ⁵ Furthermore, the impact of smoking cessation on HF reduction has not been well evaluated, particularly in Black adults. ⁸ Therefore, the purpose of this study was to investigate the relationship between smoking and incident HF subtypes, the influence of lung dysfunction on this relationship, and the relationship between smoking cessation and incident HF and HF subtypes, based on our previous research.

METHODS

Data Availability

Because of the sensitive nature of the data collected for this study, requests to access the data set from qualified researchers trained in human subject confidentiality protocols may be sent to JHS (Jackson Heart Study) at https://www.jacksonheartstudy.org/.

Jackson Heart Study Participants

The JHS (Jackson Heart Study) is a large prospective community‐based observational cohort of Black adults focused on the investigation of risk factors for cardiovascular diseases. Details of the JHS study design, recruitment, and data collection have been described previously. ⁵ , ⁹ During the baseline examination from 2000 to 2004 (Visit 1), 5306 Black participants from the Jackson, Mississippi tri‐county area (Hinds, Rankin, and Madison counties) were recruited and completed 2 subsequent study follow‐up visits (Visit 2: 2005–2008, Visit 3: 2009–2012). The JHS was approved by the Institutional Review Boards of Jackson State University, Tougaloo College, and the University of Mississippi Medical Center in Jackson, Mississippi. All study participants provided written informed consent. For the present analysis, we excluded all individuals with prevalent HF at the baseline examination, missing information on HF prevalence, or those who had already died on January 1, 2005 (n=659), those who did not consent to the researchers' use of their Visit 1 record (n=180), prevalent CHD at January 1, 2005 (n=250), or missing information on smoking status (n=28). Therefore, 4189 participants were included (Figure 1).

Figure 1. Exclusion criteria and the numbers of participants for each study.

CHD indicates coronary heart disease; HF, heart failure; and JHS, Jackson Heart Study.

Smoking Information

Self‐reported smoking information was obtained via questionnaire at Visit 1. Participants who smoked >400 cigarettes in their lifetime were defined as “ever smoking.” Participants who gave a positive response to the question, “Do you now smoke cigarettes?” were labeled as “current smoking.” Those who responded negatively to both questions were labeled as “never smoking.” ⁹ Participants who smoked >400 cigarettes but no longer smoked at the time of the examination were labeled as “former smoking.” Smoking intensity (cigarettes per day) and smoking burden (cigarette pack‐years) were also collected.

Clinical Covariates

At Visit 1, systolic and diastolic blood pressures were measured in the right arm of participants twice using the random‐0 blood pressure sphygmomanometer (Hawksley and Sons Limited, Sussex, UK). The first blood pressure was obtained after allowing the participant to rest for 5 minutes in a seated position, and the second blood pressure was obtained after waiting 1 additional minute. The average of the 2 measurements was used. Body mass index was calculated as body weight (kg)/(height [m])². Self‐reported antihypertensive medication use was collected at the time of each examination. Venous blood samples were drawn from each participant after >12 hours of fasting. Fasting plasma glucose, hemoglobin A1c, and serum creatinine levels were assessed using standard laboratory techniques. Diabetes was defined as the use of diabetes medications, a hemoglobin A1c ≥6.5%, or a fasting blood glucose ≥126 mg/dL at baseline. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. ¹⁰

Data Imputation

For participants with missing values in any covariate of interest, values were imputed using multiple imputation by chained equations (STATA 17, STATA Corp, College Station, TX).

Longitudinal Study Outcomes

The primary outcome of our study was time to incident HFpEF and HF with reduced ejection fraction (HFrEF) hospitalization. HF hospitalization surveillance began January 1, 2005 in JHS. After excluding participants who died before January 1, 2005, we assessed the cumulative incidence of HF hospitalization from January 1, 2005 through December 31, 2015. Potential HF hospitalizations were identified and adjudicated as previously described. ¹¹ In brief, hospitalization data were obtained from the hospital discharge index from all catchment area hospitals and annual follow‐up information. Hospitalization data from noncatchment area hospitals were obtained after participant consent. The self‐reported data from annual follow‐up were confirmed with the hospital discharge index data. The primary diagnoses based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes were reviewed by trained medical personnel and adjudicated by trained adjudicators based on signs and symptoms, clinical documentation, laboratory tests, chest radiographs and other imaging modalities including echocardiography, multiple gated acquisition scans, and cardiac magnetic resonance imaging scans. ¹² In this analysis, HFpEF or HFrEF was defined as left ventricular ejection fraction ≥50% or left ventricular ejection fraction <50%, respectively, based on ejection fraction during the index HF hospitalization. Incident CHD was ascertained through directed patient queries during annual telephone follow‐up and ongoing surveillance of hospitalizations and subsequently confirmed through the review of hospital records.

Lung Function Data

The following lung function measures were used for covariates:

1. Percent forced vital capacity (%FVC)

2. Forced expiratory volume in first 1 second (FEV1)/FVC ratio (FEV1%)

3. Lung dysfunction category:

   1. Normal lung function
   2. Restrictive lung dysfunction: <80% of %FVC
   3. Obstructive lung dysfunction: <70% of FEV1%
   4. Mixed lung dysfunction: compatible to the definition of both 2 and 3

Maximum values of FVC and FEV1 were selected for analysis based on recommendations from the American Thoracic Society. ¹³ Derivation of the percent predicted measures of pulmonary function measures were based on the National Health and Nutrition Examination Survey and were formulated based on the race/ethnicity, height, age, and sex of the participant. ¹⁴

Statistical Analysis

Normally distributed continuous data variables are presented with means and SDs. Non‐normally distributed continuous variables and frequencies are presented as medians with interquartile ranges and categorical variables are presented as proportions. Relationships between smoking variables and incident HF hospitalization were assessed as prospective longitudinal analyses.

Cox proportional hazards models were used to estimate the hazard ratios (HR) of incident HF and subtypes using smoking status, intensity (per 10 cigarettes/d among people who currently smoke), and burden (per 10 pack‐years among ever smokers). We further examined the relationship between smoking cessation years (time since quitting) among people who formerly smoked and incident HF using Cox models. Participants who were lost to follow‐up or died were censored. Schoenfeld residuals tested assumptions of proportionality demonstrating no deviations from proportionality. Models were constructed to evaluate associations of smoking information with HF outcomes. Model 1 adjusted for age and sex, and Model 2 additionally adjusted for body mass index, systolic blood pressure, use of antihypertension medications, history of diabetes, estimated glomerular filtration rate, and incident CHD as a time‐dependent variable. To further examine the effects of lung function and inflammation on the relationships with HF, we used the following models. Model 3: Model 2+%FVC, Model 4: Model 2+FEV1/FVC ratio, Model 5: Model 2+lung dysfunction category. We additionally assessed the following 2 models. Model 6: because heavy alcohol use is associated with an increased risk of HF, we additionally adjusted for alcohol use status (Model 6: Model 2+alcohol use status). Model 7: because smoking is associated with a higher risk of illicit drug use, additionally adjusted for illicit drug use (Model 7: Model 2+illicit drug use). Restricted cubic spline curves were used to visualize the relationship between the years since quitting smoking and incident HF and its subtypes. The analysis was adjusted using multiple covariates (Model 2). The model converged well and median and interquartile range of years since quitting smoking was 20 (27–35). We used 2 knots located at 10 and 30 years. For this analysis, the y‐axes were expressed as adjusted HRs with 95% CI.

As a sensitivity analysis, we also examined the relationship between smoking status, intensity and burden, and incident HF subtypes hospitalization. In this analysis, we used the Model 2 without adjustment for incident CHD.

All statistical analyses were performed with STATA version 17 (STATA Corp, College Station, TX). A 2‐sided P value <0.05 was considered significant.

RESULTS

Baseline Characteristics

Among the study participants (n=4189), 494 (12%) were identified as current smoking, 761 (18%) identified as former smoking, and 2934 (70%) identified as never smoking. Women were more likely to have never smoked than other smoking status groups. Those who had previously smoked were older, and had a higher prevalence of hypertension and diabetes than those who did not previously smoke. Individuals who were currently smoking had a higher prevalence of current alcohol use and a higher mean estimated glomerular filtration rate compared with other smoking status groups (Table 1).

Table 1.

Baseline Characteristics

Variable	Overall (n=4189)	Never smoking (n=2934)	Former smoking (n=761)	Current smoking (n=494)
Age, y	54±13	53±13	59±11	52±11
Female sex, n (%)	2696 (64)	2058 (70)	401 (53)	237 (48)
BMI, kg/m2	31.7±7.1	32.1±7.2	31.2±6.3	29.7±7.2
SBP, mm Hg	127±16	126±16	128±16	128±17
DBP, mm Hg	76±8	76±8	75±8	77±9
Hypertension, n (%)	2237 (53)	1522 (52)	480 (63)	235 (48)
Diabetes, n (%)	870 (21)	589 (20)	194 (26)	87 (18)
Current alcohol use, n (%)	1942 (47)	1219 (42)	373 (49)	350 (71)
FEV1%, (%)	81±9	81±9	79±9	78±11
%FVC, (%)	91±17	92±17	92±17	89±18
Lung dysfunction types, n (%)
Normal	3055 (76)	2168 (77)	563 (78)	324 (70)
Restrictive only	40 (1)	21 (1)	7 (1)	12 (3)
Obstructive only	574 (14)	411 (15)	95 (13)	68 (15)
Mixed	327 (8)	210 (7)	57 (8)	60 (13)
Tc/HDL ratio	4.1±1.3	4.1±1.3	4.2±1.4	4.3±1.4
eGFR, mL/min per 1.73 m2	96±20	96±20	92±20	101±19
Average number of cigarettes/d			10 [6–20]	10 [8–20]
Pack‐y of cigarettes			13 [6–25]	18 [9–31]

The values depicted are number (%), mean±SD, and [25th–75th percentile]. BMI indicates body mass index; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FEV, forced expiratory volume; FVC, forced vital capacity; SBP, systolic blood pressure; and Tc/HDL ratio, total cholesterol/high‐density lipoprotein cholesterol ratio. The numbers present here are those before the imputation.

Regarding lung function, both FEV1% and %FVC were lower in the current smoking group than the never smoking group. The prevalence of obstructive and restrictive lung dysfunction was comparable between the groups, but the prevalence of mixed lung dysfunction was higher in the current smoking group than the never smoking group (Table 1).

Smoking Status, Intensity and Burden, and Incident HF Hospitalizations

Over a median follow‐up of 12.0 years (interquartile range, 11.2–12.0 years), there were 317 incident HF hospitalizations (incidence rate: 7.16 per 1000 person‐years). Current smoking was associated with increased incident HF hospitalizations after adjustment for conventional risk factors and incident CHD as a time‐dependent variable (HR, 2.54 [95% CI, 1.81–3.58]) (Table 2, Model 2). Furthermore, both smoking intensity among current smoking (HR, 1.46/10 cigarettes/d, [95% CI, 1.22–1.74]) and burden among ever smoking (HR, 1.07/10 pack‐years [95% CI, 1.00–1.14]) were associated with incident HF hospitalization in multivariable analyses (Table 3).

Table 2.

Smoking Status and Incident HF Hospitalization

Smoking status	Never smoking	Former smoking	Current smoking
Model		HR (95% CI)	HR (95% CI)
Model 1	Ref (1)	1.19 (0.91–1.55)	1.83 (1.31–,2.56)*
Model 2	Ref (1)	1.25 (0.95–1.64)	2.54 (1.81–3.58)*
Model 3	Ref (1)	1.26 (0.96–1.65)	2.49 (1.77–3.51)*
Model 4	Ref (1)	1.25 (0.95– 1.64)	2.41 (1.71–3.40)*
Model 5	Ref (1)	1.28 (0.98–1.69)	2.41 (1.71–3.40)*

Model 1: adjusted for age and sex. Model 2: further adjusted for systolic blood pressure, antihypertensive medication use, body mass index, diabetes, estimated glomerular filtration rate, and incident coronary heart disease as a time‐dependent variable. Model 3: Model 2+FEV1%. Model 4: Model 2+%FVC. Model 5: Model 2+lung dysfunction category. FEV indicates forced expiratory volume; FVC, forced vital capacity; HF, heart failure; and HR, hazard ratio.

^* P <0.01.

Table 3.

Smoking Intensity Among Current Smoking, Burden Among Ever Smokings, and Incident HF hospitalization

Smoking variables	Never smoker	Smoking intensity, per 10 cigarette/d among current smoking	Smoking burden, per 10 pack y among ever smoking
Model		HR (95%CI)	HR (95% CI)
Model 1	Ref (1)	1.29 (1.07–1.56)†	1.07 (0.99–1.14)
Model 2	Ref (1)	1.46 (1.22–1.74)†	1.07 (1.00–1.14)*
Model 3	Ref (1)	1.45 (1.21–1.74)†	1.07 (1.00–1.14)
Model 4	Ref (1)	1.42 (1.19–1.71)†	1.06 (0.99–1.14)
Model 5	Ref (1)	1.43 (1.20–1.73)†	1.06 (0.99–1.14)

Model 1: adjusted for age and sex. Model 2: further adjusted for systolic blood pressure, antihypertensive medication use, body mass index, diabetes, estimated glomerular filtration rate, and incident coronary heart disease as a time‐dependent variable. Model 3: Model 2+FEV1%. Model 4: Model 2+%FVC. Model 5: Model 2+lung dysfunction category. FEV indicates forced expiratory volume; FVC, forced vital capacity; HF, heart failure; and HR, hazard ratio.

^* P <0.05.

^† P <0.01.

Smoking Status, Intensity and Burden, and Incident HF Subtypes

During the follow‐up period, there were 133 incident HFrEF and 145 incident HFpEF hospitalizations (incidence rate: HFrEF, 3.00 per 1000 person‐years, HFpEF, 3.27 per 1000 person‐years). Current smoking was associated with both increased incident HFrEF and HFpEF hospitalizations after adjustment for conventional risk factors and incident CHD as a time‐dependent variable (HFrEF HR, 2.04 [95% CI, 1.25–3.34], HFpEF HR, 2.95 [95% CI, 1.73–5.02]); (Table 4, Model 2). Furthermore, both smoking intensity among current smoking (HR, 1.58/cigarettes per day [95% CI, 1.22–2.04]) and smoking burden among ever smoking (HR, 1.12/pack‐years [95% CI, 1.02–1.23]) were significantly associated with incident HFpEF hospitalization in multivariable analyses (Table 5, Model 2). However, they were not significantly associated with incident HFrEF (Table 5, Model 2).

Table 4.

Smoking Status and Incident HFrEF or HFpEF

Smoking status	Never smoking	Former smoking	Current smoking
Model		HR (95% CI)	HR (95% CI)
HFrEF
Model 1	Ref (1)	0.92 (0.60–1.42)	1.67 (1.03–2.71)*
Model 2	Ref (1)	0.97 (0.63–1.50)	2.04 (1.25–3.34)†
Model 3	Ref (1)	0.98 (0.63–1.51)	2.00 (1.22–3.28)†
Model 4	Ref (1)	0.97 (0.62–1.50)	1.89 (1.15–3.11)†
Model 5	Ref (1)	0.98 (0.63–1.52)	1.94 (1.18–3.19)†
HFpEF
Model 1	Ref (1)	1.39 (0.94–2.04)	1.87 (1.11–3.14)*
Model 2	Ref (1)	1.45 (0.98–2.15)	2.95 (1.73–5.02)†
Model 3	Ref (1)	1.47 (0.99–2.17)	2.87 (1.68–4.90)†
Model 4	Ref (1)	1.45 (0.98–2.15)	2.85 (1.67–4.87)†
Model 5	Ref (1)	1.52 (1.02–2.25)*	2.82 (1.65–4.83)†

Model 1: adjusted for age and sex. Model 2: further adjusted for systolic blood pressure, antihypertensive medication use, body mass index, diabetes, estimated glomerular filtration rate, and incident coronary heart disease as a time‐dependent variable. Model 3: Model 2+FEV1%. Model 4: Model 2+%FVC. Model 5: Model 2+lung dysfunction category. FEV indicates forced expiratory volume; FVC, forced vital capacity; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and HR, hazard ratio.

^* P <0.05.

^† P <0.01.

Table 5.

Smoking Intensity Among Current Smokers, Burden Among Ever Smokers, and Incident HFrEF or HFpEF

Smoking status	Never smoking	Smoking intensity, per 10 cigarette/d among current smoking	Smoking burden, per 10 pack y among ever smoking
Model		HR (95% CI)	HR (95% CI)
HFrEF
Model 1	Ref (1)	1.18 (0.89–1.55)	1.01 (0.89–1.15)
Model 2	Ref (1)	1.31 (1.00–1.73)	1.01 (0.90–1.15)
Model 3	Ref (1)	1.30 (0.98–1.71)	1.01 (0.89–1.14)
Model 4	Ref (1)	1.27 (0.96–1.68)	1.00 (0.89–1.13)
Model 5	Ref (1)	1.30 (0.98–1.72)	1.01 (0.89–1.15)
HFpEF
Model 1	Ref (1)	1.42 (1.07–1.88)*	1.11 (1.01–1.22)*
Model 2	Ref (1)	1.58 (1.22–2.04)†	1.12 (1.02–1.23)*
Model 3	Ref (1)	1.57 (1.22–2.03)†	1.11 (1.02–1.22)*
Model 4	Ref (1)	1.56 (1.21–2.01)†	1.11 (1.01–1.22)*
Model 5	Ref (1)	1.59 (1.22–2.06)†	1.11 (1.01–1.21)*

Model 1: adjusted for age and sex. Model 2: further adjusted for systolic blood pressure, antihypertensive medication use, body mass index, diabetes, estimated glomerular filtration rate, and incident coronary heart disease as a time‐dependent variable. Model 3: Model 2+FEV1%. Model 4: Model 2+%FVC. Model 5: Model 2+lung dysfunction category. FEV indicates forced expiratory volume; FVC, forced vital capacity; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and HR, hazard ratio.

^* P <0.05.

^† P <0.01.

The results of the sensitivity analyses are shown in Tables S1 and S2. Even without adjustment for incident CHD, the results were not significantly changed.

Additional Adjustment for Lung Function Variables

After adjustment for %FVC, FEV1%, or lung dysfunction category at Visit 1, the associations between smoking status, intensity, and burden with incident HF were not significantly influenced (Tables 2 and 3, Model 3 to Model 5). There were similar findings with smoking variables and incident HF subtypes after adjustment for lung function measures (Tables 4 and 5, Model 3 to Model 5).

Additional Adjustment for Alcohol Use and Illicit Drug Use

After adjustment for alcohol use status or illicit drug use at Visit 1, the associations between smoking status, intensity, and burden with incident HF were not significantly influenced (Tables S3 through S6).

Cigarette Smoking Cessation and the Risk of Incident HF

Among former smoking, the risk of developing HF decreased with increasing duration of smoking cessation. It takes ≈15 years for the risk to be halved from the time of last smoking (Figure 2). Similar associations were observed for both subtypes of HF (Figure 2).

Figure 2. Smoking cessation and risk of incident heart failure.

More than 15 years of smoking cessation is necessary to significantly reduce the risk of developing HF. CI indicates confidence interval; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and HR, hazard ratio.

DISCUSSION

In a large community‐based cohort of Black adults, current smoking was associated with both incident HFrEF and HFpEF hospitalization after adjustment for possible confounding factors including incident CHD and lung function. Smoking intensity among current smoking and smoking burden among ever smoking were significantly associated with incident HFpEF, whereas they were not significantly associated with incident HFrEF. Lung function variables did not significantly affect the relationship between smoking and incident HF subtypes. The risk of developing HF decreased with the duration of smoking cessation among former smoking.

We have previously reported that current smoking was associated with incident HF after adjustment for possible confounding factors including incident CHD. ⁵ Furthermore, smoking intensity among current smoking and smoking burden among ever smoking were also dose‐dependently associated with incident HF. In the present analysis, based on our previous study, we have further investigated the relationship between smoking and HF subtypes. In this study, current smoking was associated with both subtypes of incident HF (HFrEF and HFpEF). To our knowledge, the present study is the first to report these findings among a large community‐based cohort of Black adults.

In community‐based cohorts, including CHS (Cardiovascular Health Study), PREVEND (Prevention of Renal and Vascular Endstage Disease), FHS (Framingham Heart Study), and MESA (Multi‐Ethnic Study of Atherosclerosis), current smoking was associated with incident HFrEF, but not with HFpEF. ¹⁵ In contrast, in another report from the FHS, Ho and colleagues found that current smoking was associated with incident HFpEF, but not with HFrEF. ¹⁶ Recently Ding and colleagues reported that compared with never smoking, current smoking was associated with both HFpEF and HFrEF in the ARIC (Atherosclerosis in Communities Study). ¹⁷ In the former study including 4 large community cohorts, HFpEF was defined using the cut point left ventricular ejection fraction >45%, and this may have led to more cases defined as HFpEF, thereby affecting the association with current smoking. In addition, Black participants accounted for <10% of people included in their analysis; therefore, racial differences noted between our study and this study may have influenced the observed findings. In FHS, Ho and colleagues included participants with prevalent CHD. They adjusted for prevalent CHD, but not for incident CHD in their analyses. These factors may have made current smoking more likely to be associated with HFrEF. In the ARIC study, Ding and colleagues included participants with prevalent CHD and adjusted for prevalent and incident CHD in their analyses. This approach is similar to our study with regard to carefully considering the influences of CHD. While there was a significant difference in race between the Ding study and our study, the HR of current smoking was similar, and current smoking was associated with both with HFpEF and HFrEF in both studies.

Based on our results, smoking intensity among current smoking and pack‐years among ever smoking were associated with incident HFpEF, but not with HFrEF. These results were different from the results of Ding's report. Although we did not observe a significant relationship between smoking intensity among current smoking and pack‐years among ever smoking and incident HFrEF, there was a trend. In the present study, patients with CHD were originally excluded and we also adjusted for incident CHD during follow‐up. Therefore, the influences of CHD would have been minimized. In addition, smoking has been associated with respiratory dysfunction including chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease has been more associated with HFpEF. In this study, there was no change in the association between smoking and both subtypes of HF before and after adjustment for respiratory function indices. Overall, the cause of the difference in the relationship between smoking intensity and burden and incident subtypes of HF in the present study has not been well elucidated, but the relatively small number of events (both incident HFpEF and HFrEF) may have influenced the results.

In our previous study, current smoking was associated with left ventricular concentric remodeling and an increase in left ventricular mass index. ⁵ Similar observations were noted in the ARIC study, suggesting a potential association between smoking and left ventricular concentric hypertrophy. ¹⁸ Left ventricular concentric hypertrophy is a risk factor for the onset of HF, and there is a possibility that it might have mediated the observed relationship between smoking and the development of HF in this study. ¹⁹

In a recent study, lung dysfunction has been associated with incident HF, especially incident HFpEF. ²⁰ In our study, even after additionally adjusting for lung function variables, smoking was still associated with incident HF and both HF subtypes. The influences of smoking on lung dysfunction are obvious. Our findings suggest that smoking is associated with incident HF and HF subtypes independent of the influences of smoking on lung dysfunction. However, it is important to consider that lung function was evaluated at Visit 1 (baseline); continued smoking or changes in smoking intensity and subsequent changes in lung function over time may influence this relationship.

In our study, the risk of developing HF decreased with duration of smoking cessation among former smoking. It takes ≈15 years for the risk to be halved from the time of last smoking. Previous studies have reported the association between years after quitting cigarette smoking and the risk of incident HF. In the CHS, after >15 years of smoking cessation, the risk of HF and death for former smoking was similar to that of never smoking. ²¹ However, in the ARIC Study, there was a dose–response relationship for the duration of smoking cessation and risk of HF, and the residual risk persisted for a few decades for 2 phenotypes of HF. ¹⁷ Although the results of our study and these studies cannot be compared easily due to different end points and analytic methods, it appears that >15 years of smoking cessation is necessary to significantly reduce the risk of developing HF. Smoking has been strongly linked to cardiovascular diseases; however, the strong link with HFpEF, particularly, has been underrecognized by clinicians. Thus, current smokers with HF or those at risk of developing HF need to be counseled about this risk. Given the higher rates of HF and worse outcomes in Black people with HF, smoking cessation and prevention of smoking should be targeted and promoted better in Black people.

In our study, current smoking was associated with the development of both subtypes of HF. Smoking intensity in current smoking and pack‐years in former smoking were associated with the onset of HFpEF, but there was no statistically significant association with HFrEF.

Although the prevalence of HFpEF has been increasing, therapeutic strategies have been limited. Therefore, prevention is important for this type of HF. Our results suggest that quitting smoking or reducing smoking intensity and pack‐years may reduce the development of HF, especially HFpEF.

Our study has some limitations. First, self‐reported smoking status was not confirmed with cotinine levels, which are currently unavailable in JHS. Second, we have not asked about nondaily smoking. Therefore, if there were nondaily smokers included in former smokers, it could dilute the impact of active smoking and increase the risk of former smoking. Third, in the JHS, never smoking was defined as <400 cigarettes in a lifetime compared with many studies using a cut point of 100 cigarettes in a lifetime, which could impact the definition and comparisons of never and former smoking. Fourth, smoking has been associated with nonadherence to medications. This could result in less well‐controlled hypertension over time, and poorer adherence to medication for HF, leading to more HF hospitalizations. Fifth, there may be some participants whose smoking status was changed during the follow‐up period. Sixth, our data were obtained from an all‐Black cohort in the metro Jackson, MS area and may not be generalizable to other ethnic or racial groups or other regions. Seventh, unmeasured confounding may have influenced the results. Eighth, it is also possible that HF cases may have been missed (or misclassified); however, the definition for HF that was utilized has been previously used and validated in other JHS analyses as well as in the ARIC Study

CONCLUSIONS

In our large community‐based cohort of Black adults, current smoking was associated with both incident HFrEF and HFpEF hospitalizations. Smoking intensity among current smoking and smoking burden among former smoking were significantly associated with incident HFpEF, whereas they were not significantly associated with incident HFrEF. These associations were independent of the effects of smoking on lung function. It takes >15 years of cigarette smoking cessation to significantly reduce the risk of developing HF.

Sources of Funding

The Jackson Heart Study (JHS) is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities (NIMHD). M.E.H. has also received support from NIH/NIDDK 1K08DK099415‐01A1 and NIH/NIGMS P20GM104357.

Disclosures

None.

JHS Disclaimer

The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services.

Supporting information

Tables S1–S6