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Figure 1.  Effect Modification of Comorbid Conditions on the Association Between Smoking and Any Complication in the Propensity Score–Matched Cohort
Effect Modification of Comorbid Conditions on the Association Between Smoking and Any Complication in the Propensity Score–Matched Cohort

Heterogeneity of smoking association visualized by forest plot of matched odds ratios and 95% CIs for any 30-day complication by prespecified subgroup and overall. The dotted vertical line represents an odds ratio of 1.00, indicating no difference between smoking and nonsmoking groups. The dashed vertical line represents the overall matched odds ratio for the association of smoking with any 30-day complication. COPD indicates chronic pulmonary obstructive disease; CVD, cardiovascular disease.

aP value of the interaction term.

bAmong patients with infrainguinal disease, there were 5194 femoral/popliteal interventions (96.6%) and 190 tibial interventions (3.4%).

Figure 2.  Complication by Severity and System in Propensity Score–Matched Cohort
Complication by Severity and System in Propensity Score–Matched Cohort

Complications by severity (A) and wound, respiratory, and thrombosis complications (B) were significantly higher among smokers compared with nonsmokers. Error bars indicate 95% CIs.

aComplication categorization defined in eTable 3 in the Supplement.

bComplication system defined in eTable 4 in the Supplement.

cGraft failure is a subset of the thrombosis-related complications category.

Figure 3.  Any Complication by Smoking Exposure and Intervention Type Among the Full Cohort Eligible for Propensity Score Match
Any Complication by Smoking Exposure and Intervention Type Among the Full Cohort Eligible for Propensity Score Match

Heterogeneity of smoking timeframe visualized by forest plot of adjusted odds ratios and 95% CIs for any 30-day complication comparing active smokers (smoking within 2 weeks before the procedure) with never smokers and with former smokers (more than 1 year cessation) overall and by treatment modality. There were a total of 4417 endovascular revascularizations (30.8%), 4319 hybrid revascularizations (30.1%), and 5614 open revascularizations (39.1%). The dotted vertical line represents an odds ratio of 1.00, indicating no difference between timeframe exposure groups. The dashed vertical lines indicate the overall active vs never smoking (top) and active vs former smoking (bottom) adjusted odds ratios. Error bars indicate 95% CIs.

aCigarette smoking exposure timeframe is available only in the 2012 to 2019 Veterans Affairs Quality Improvement Program data sets (n = 13 184). Analysis included those with cigarette smoking timeframe available (n = 12 794 [97.0%]) and excluding those who stopped smoking between 2 and 52 weeks prior to the procedure (n = 1669 [12.7%]). Adjusted odds ratios generated after controlling for baseline demographic characteristics, including age, sex, race, ethnicity, and body mass index; comorbid conditions, including stroke, congestive heart failure, hypertension, diabetes, alcohol use, and frailty; history of lower extremity revascularization or amputation for ischemia and percutaneous coronary intervention; preprocedural hematocrit level; hospital complexity level; procedure stress and intervention type; and procedure year.

bThe interaction P value overall and by intervention modalities by exposure subgroups.

Table 1.  Preprocedural Patient and Hospital Characteristics
Preprocedural Patient and Hospital Characteristics
Table 2.  30-Day Outcomes in Propensity Score–Matched Cohort and Full Cohort Eligible for Matching
30-Day Outcomes in Propensity Score–Matched Cohort and Full Cohort Eligible for Matching
Supplement.

eTable 1. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM procedure diagnosis codes identifying intermittent claudication.

eTable 2. Current Procedural Terminology codes, descriptions, and Operative Stress Scores identifying revascularization procedures.

eTable 3. Postprocedural complications quantified within the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and their associated categorization—by major or minor complication.

eTable 4. Postprocedural complications quantified within the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and their associated categorization—by organ system.

eTable 5. Preprocedural variable missingness for all patients eligible for propensity score matching.

eTable 6. Demographic, patient, procedure, and surgical site characteristics included in propensity score matching.

eTable 7. Baseline characteristics of smoking (n = 7820) and nonsmoking (n = 6530) patients who were included (n = 8420) and excluded (n = 7049) from propensity sore matching.

eTable 8. Multivariable logistic regression for any postprocedural complication among all patients eligible for propensity score matching (N = 14 350).

eTable 9. Patient characteristics by smoking timeframe (N = 12 794).

eFigure 1. Cohort identification.

eFigure 2. Revascularization for claudication by intervention (A) and by smoking status (B) per year in the full cohort eligible for propensity score matching.

eFigure 3. Distribution of propensity score before (N = 14 350) and after (n = 7710) propensity score matching.

eFigure 4. Standardized percentage bias across covariates among matched (n = 7710) and unmatched (n = 7301) cohorts.

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Original Investigation
October 6, 2021

Association of Smoking With Postprocedural Complications Following Open and Endovascular Interventions for Intermittent Claudication

Author Affiliations
  • 1Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 2Division of Vascular Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 3Department of Surgery, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
  • 4University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 5Department of Cardiology, Johns Hopkins, Baltimore, Maryland
  • 6Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California
  • 7Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
  • 8Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire
  • 9Department of Surgery, UT Health San Antonio, University of Texas, San Antonio
  • 10Department of Surgery, South Texas Veterans Health Care System, San Antonio
  • 11Center for Health Equity Research and Promotion, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
  • 12Wolff Center at UPMC, Pittsburgh, Pennsylvania
JAMA Cardiol. 2022;7(1):45-54. doi:10.1001/jamacardio.2021.3979
Key Points

Question  Does smoking prior to elective revascularization for intermittent claudication (IC) increase the risk of early postprocedural complications?

Findings  In this cohort study including 14 350 revascularizations (open or endovascular) for IC, more than half of patients were smoking prior to the procedure. Overall, smoking within 1 year of the procedure was associated with a 48% increase in the risk of any early postprocedural complication; compared with active smokers (smoking within 2 weeks before the procedure), the risk of any complication was decreased by 65% for never smokers and by 29% for former smokers (more than 1 year cessation).

Meaning  In this study, smoking was associated with an increased risk of early postprocedural complications; smoking cessation should be emphasized prior to elective revascularization for IC.

Abstract

Importance  Smoking is a key modifiable risk factor in the development and progression of peripheral artery disease, which often manifests as intermittent claudication (IC). Smoking cessation is a first-line therapy for IC, yet a minority of patients quit smoking prior to elective revascularization.

Objective  To assess if preprocedural smoking is associated with an increased risk of early postprocedural complications following elective open and endovascular revascularization.

Design, Setting, and Participants  This retrospective cohort study used nearest-neighbor (1:1) propensity score matching of 2011 to 2019 data from the Veterans Affairs Surgical Quality Improvement Program, including all cases with a primary diagnosis of IC and excluding emergent cases, primary procedures that were not lower extremity revascularization, and patients with chronic limb-threatening ischemia within 30 days of the intervention. All data were abstracted June 18, 2020, and analyzed from July 26, 2020, to June 30, 2021.

Exposures  Preprocedural cigarette smoking.

Main Outcomes and Measures  Any and organ system–specific (ie, wound, respiratory, thrombosis, kidney, cardiac, sepsis, and neurological) 30-day complications and mortality, overall and in prespecified subgroups.

Results  Of 14 350 included cases of revascularization, 14 090 patients (98.2%) were male, and the mean (SD) age was 65.7 (7.0) years. A total of 7820 patients (54.5%) were smoking within the preprocedural year. There were a total of 4417 endovascular revascularizations (30.8%), 4319 hybrid revascularizations (30.1%), and 5614 open revascularizations (39.1%). A total of 1594 patients (11.1%) had complications, and 57 (0.4%) died. Among 7710 propensity score–matched cases (including 3855 smokers and 3855 nonsmokers), 484 smokers (12.6%) and 34 nonsmokers (8.9%) experienced complications, an absolute risk difference (ARD) of 3.68% (95% CI, 2.31-5.06; P < .001). Compared with nonsmokers, any complication was higher for smokers following endovascular revascularization (26 [4.3%] vs 52 [2.1%]; ARD, 2.19%; 95% CI, 0.77-3.60; P = .003), hybrid revascularization (204 [17.3%] vs 163 [14.1%]; ARD, 3.18%; 95% CI, 0.23-6.13; P = .04), and open revascularization (228 [15.4%] vs 153 [10.3%]; ARD, 5.18%; 95% CI, 2.78-7.58; P < .001). Compared with nonsmokers, respiratory complications were higher for smokers following endovascular revascularization (20 [1.7%] vs 6 [0.5%]; ARD, 1.17%; 95% CI, 0.35-2.00; P = .009), hybrid revascularization (33 [2.8%] vs 10 [0.9%]; ARD, 1.93%; 95% CI, 0.85-3.02; P = .001), and open revascularization (32 [2.2%] vs 19 [1.3%]; ARD, 0.89%; 95% CI, 0-1.80; P = .06). Wound complications and graft failure were higher for smokers compared with nonsmokers following open interventions (wound complications: 146 [9.9%] vs 87 [5.8%]; ARD, 4.05%; 95% CI, 2.12-5.99; P < .001; graft failure: 33 [2.2%] vs 11 [0.7%]; ARD, 1.50%; 95% CI, 0.63-2.37; P = .001). In a sensitivity analysis, compared with active smokers (n = 5173; smoking within 2 weeks before the procedure), the risk of any complication was decreased by 65% for never smokers (n = 1197; adjusted odds ratio, 0.45; 95% CI, 0.34-0.59) and 29% for former smokers (n = 4755; cessation more than 1 year before the procedure; adjusted odds ratio, 0.71; 95% CI, 0.61-0.83; P = .001 for interaction).

Conclusions and Relevance  In this cohort study, more than half of patients with IC were smoking prior to elective revascularization, and complication risks were higher across all modalities of revascularization. These findings stress the importance of smoking cessation to optimize revascularization outcomes.

Introduction

Peripheral artery disease (PAD) affects more than 230 million people worldwide and is particularly prevalent among US veterans owing to high rates of tobacco use.1,2 PAD often manifests as intermittent claudication (IC), defined as ischemic muscle pain with activity.3 Atherosclerosis is a systemic disease that affects coronary, cerebral, and peripheral arteries and confers increased risk of cardiovascular disease (CVD)–related morbidity and mortality.2,4 Proinflammatory and prothrombotic effects of cigarette smoking4,5 on PAD contribute to earlier disease onset and progression, limb loss, functional decline, reduced quality of life, and 20% of CVD deaths in the US.3,6-12

Evidence-based IC treatment guidelines focus primarily on mitigation of associated CVD morbidity and mortality and secondarily on relief of IC.13,14 The former involves clear prioritization of optimal medical therapy (OMT), which includes smoking cessation.15-18 If IC symptoms persist following OMT, revascularization may be considered. Yet despite the unknown effectiveness, lack of durability, elective nature of revascularization for IC, and known benefits of OMT, nearly two-thirds of patients are not medically optimized prior to revascularization.18,19

Our primary objective was to determine the association between smoking and 30-day postprocedural complications following elective revascularization for IC. Secondarily, we evaluated the use of endovascular and open revascularization for IC over time. We hypothesized that a large proportion of patients undergoing revascularization for IC were smokers and that smoking was associated with an increased risk of early postprocedural complications across all intervention types.

Methods

We used deidentified 2011 to 2019 data from the Veterans Affairs Surgical Quality Improvement Program (VASQIP) in this retrospective cohort study, determined to be exempt by the Veterans Affairs Pittsburgh Healthcare System Institutional Review Board. All data were abstracted June 18, 2020, and analyzed from July 26, 2020, to June 30, 2021. Data are reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.20

Data Source

The VASQIP comprises a systematic and representative sampling of veterans undergoing interventions at all Veterans Affairs surgical centers.21,22 Each center is mandated to randomly sample up to 6 cases per procedure type and more than 36 cases overall every 8-day cycle, deliberately and systematically oversampling uncommon procedures. Each patient is observed for 30 postprocedural days.

The VASQIP includes patient-level data including more than 200 variables, described in detail by the Veterans Affairs National Surgery Office,22 capturing demographic, medical, surgical center, and procedure data and postprocedure complications in conjunction with healthy user indicators representing health habits (eg, alcohol use) and functionality (eg, activities of daily living, nursing residence).23 We expanded these data to capture otherwise unmeasured potential confounding, including (1) patient frailty, (2) physiologic stress of the intervention, (3) intervention modality, (4) anatomic level of revascularized PAD, and surgical center specific measures of (5) patient rurality and (6) site complexity. We assessed patient frailty and the physiologic stress of the principal procedure with the validated Risk Analysis Index24 and Operative Stress Score,25,26 which independently and synergistically predict postprocedural complications.24-27 The principal procedure Current Procedural Terminology code defined the intervention modality (ie, endovascular or open) and was recategorized as hybrid if the case had multiple Current Procedural Terminology codes including both modalities. The most proximal intervention defined the anatomic level of revascularized PAD. Surgical site rurality and complexity level were quantified, capturing health care access inequalities and socioeconomic status.28,29 We quantified rurality by Rural-Urban Commuting Areas and the Veterans Health Administration Office of Rural Health Rurality Calculator.30 Surgical center complexity level was determined by the highest designation of procedure complexity, volume, and infrastructure capabilities.31

Cohort Identification

We included all noncardiac cases in the VASQIP (January 3, 2011, to September 30, 2019) with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM preprocedural diagnosis of IC (eTable 1 in the Supplement) and a principal revascularization procedure (eTable 2 in the Supplement). Our final cohort included only elective cases, excluding (1) patients with preprocedural chronic limb-threatening ischemia and/or (2) American Society of Anesthesiologists Score emergency designation.

Study Exposure and Outcome

Veterans were classified as smokers if the VASQIP abstractor adjudicated that the patient smoked cigarettes within 1 year or as nonsmokers (ie, former and never) if they did not smoke within 1 year prior to admission. The primary outcome was any 30-day postprocedural complication.32 Thirty-day secondary outcomes included major and minor complications (eTable 3 in the Supplement), complications by organ system (eTable 4 in the Supplement), and mortalitly.32

Statistical Analysis

We expressed categorical variables as counts and percentages and continuous variables as means and SDs or medians and IQRs. Proportions of missing data stratified by smoking status were also quantified.

To minimize the potential bias of smoking status on comorbid conditions and confounding, we generated a propensity score to quantify the likelihood patients had for smoking using covariates determined a priori.33 We included all data available throughout the study timeframe and excluded variables (1) affecting less than 0.1% of patients eligible for matching, (2) with more than 5% missingness, which could not be assumed to be missing at random, or (3) potentially representing the proinflammatory and prothrombotic effects of smoking (ie, causal pathway).

We generated a matched population of smokers and nonsmokers using a 1:1 nearest-neighbor matching algorithm with calipers of 0.02, without replacement.34-36 We compared preprocedural patient, procedure, and treatment center characteristics before and after matching using a standardized difference (less than 0.15 considered acceptable).34,37 We also compared characteristics among the patients included and excluded from the match.

In the matched cohort, we quantified the frequency of postprocedural outcomes with and without stratification by intervention modality and anatomic level of disease. We calculated the absolute risk difference (ARD) and compared outcomes using the McNemar test.38 We used logistic regression with the robust variance estimator to calculate matched odds ratios (ORs) for postprocedural complications. The effects of smoking were assessed among patients from self-identified racial minority groups and with prespecified comorbid conditions, including (1) chronic obstructive pulmonary disease (COPD), (2) comorbid CVD (ie, myocardial infarction, congestive heart failure, and stroke), (3) diabetes, (4) frailty (ie, nonfrail [Risk Analysis Index less than 30] and frail [Risk Analysis Index of 30 or more]), (5) intervention modality, and (6) level of revascularization. Significance was set at a P value less than .05, and all P values were 2-tailed.

Sensitivity Analysis

We evaluated the robustness of our results in sensitivity analyses. First, we calculated the E-value quantifying the effect size magnitude required for a potential unmeasured confounder to negate the observed association between smoking and any postprocedural complication.39,40 Second, we evaluated alternative definitions of any and major (ie, Clavien-Dindo grade IV) postprocedural complications.41 Third, we calculated adjusted ORs of complications in the full cohort eligible for matching to account for the reduction in sample size inherent to the matching methodology. Finally, we evaluated outcomes among all patients eligible for matching with a known smoking timeframe. We calculated adjusted ORs for any postprocedural complication among those who (1) actively smoked (within 2 weeks of the procedure), (2) formerly smoked (cessation more than 1 year before the procedure), and (3) never smoked overall and by intervention modality. All analyses were conducted using Stata version 15.1 (StataCorp) and Prism version 7.0 (GraphPad).

Results

We identified 20 266 cases of revascularization for IC. Of 14 350 included cases of elective revascularizations, 14 090 patients (98.2%) were male, 4490 (31.3%) had concurrent CVD, and the mean (SD) age was 65.7 (7.0) years. A total of 7820 patients (54.5%) were smoking within the preprocedural year (eFigure 1 in the Supplement). Patients with IC and concurrent CVD had a lower rate of smoking (2259 of 4490 [50.3%]) compared with those without CVD (5589 of 9860 [56.7%]; P < .001). There were a total of 4417 endovascular revascularizations (30.8%), 4319 hybrid revascularizations (30.1%), and 5614 open revascularizations (39.1%); and there were 4514 cases (31.6%) of suprainguinal disease and 9780 (68.4%) of infrainguinal disease. Case numbers increased over time (mean [SD] change per year, 98 [234]) with a dramatic rise in the proportion of endovascular revascularizations (mean [SD] change per year, 5.0% [8.8%]) and a progressive decline in open revascularization (mean [SD] change per year, −3.4% [7.9%]; eFigure 2 in the Supplement). Overall, 1594 cases (11.1%) resulted in any complication, and 57 (0.4%) resulted in death by 30 days.

Characteristics according to smoking status are summarized in Table 1 with variable missingness quantified in eTable 5 in the Supplement. In the full cohort eligible for matching, compared with nonsmokers, smokers were younger, more likely to be from a racial and ethnic minority group and have COPD, and less likely to have CVD, diabetes, and frailty. Smokers underwent more physiologically stressful open and hybrid interventions. The rate of smoking for each intervention type was consistent over time (eFigure 2 in the Supplement).

After propensity score matching (3855 smokers and 3855 nonsmokers), characteristics were equally distributed between groups (Table 1; eTable 6 and eFigures 3 and 4 in the Supplement). Compared with matched nonsmokers, unmatched nonsmokers were older, more likely to be White and have CVD, and less likely to have COPD. Unmatched smokers demonstrated an opposite trend (eTable 7 in the Supplement).

Outcomes in the Propensity Score–Matched Cohort

Smokers had a higher risk of any 30-day postprocedural complication compared with nonsmokers (484 [12.6%] vs 34 [8.9%]), with an ARD of 3.68% (95% CI, 2.31-5.06; P < .001). The increased risk for smokers was observed across subgroups; compared with nonsmokers, any complication was higher for smokers following endovascular revascularization (26 [4.3%] vs 52 [2.1%]; ARD, 2.19%; 95% CI, 0.77-3.60; P = .003), hybrid revascularization (204 [17.3%] vs 163 [14.1%]; ARD, 3.18%; 95% CI, 0.23-6.13; P = .04), and open revascularization (228 [15.4%] vs 153 [10.3%]; ARD, 5.18%; 95% CI, 2.78-7.58; P < .001) (Figure 1). However, the risk of any complication among smokers was significantly increased for non-White Hispanic patients and those with COPD and nonfrail status compared with non-Hispanic White patients and those without COPD and frailty.

In evaluating secondary outcomes, smokers had a higher risk of major, minor, wound, respiratory, and thrombotic complications compared with nonsmokers (Figure 2; Table 2). Compared with nonsmokers, respiratory complications were higher for smokers following endovascular revascularization (20 [1.7%] vs 6 [0.5%]; ARD, 1.17%; 95% CI, 0.35-2.00; P = .009), hybrid revascularization (33 [2.8%] vs 10 [0.9%]; ARD, 1.93%; 95% CI, 0.85-3.02; P = .001), and open revascularization (32 [2.2%] vs 19 [1.3%]; ARD, 0.89%; 95% CI, 0-1.80; P = .06). However, wound and thrombotic complications were only significantly higher for smokers compared with nonsmokers undergoing open procedures (wound: 146 [9.9%] vs 87 [5.8%]; ARD, 4.05%; 95% CI, 2.12-5.99; P < .001; thrombotic: 41 [2.8%] vs 16 [1.1%]; ARD, 1.71%; 95% CI, 0.72-2.69; P = .001). Notably, the risk of vascular graft failure was also significantly higher for smokers compared with nonsmokers undergoing open revascularization (33 [2.2%] vs 11 [0.7%]; ARD, 1.50%; 95% CI, 0.63-2.37; P = .001). Smoking was associated with increased 30-day mortality (23 [0.6%] vs 2 [0.1%]; ARD, 0.54%; 95% CI, 0.29-0.80).

Sensitivity Analysis

Our results in the propensity score–matched cohort were robust to both potential confounders and alterative definitions of the outcomes. The E-value indicates a single unmeasured confounder with an ARD greater than 2.13% or an OR greater than 2.21 is required to negate the association between smoking and any complication. In the matched cohort, the association between smoking and complications persisted when altering the definition of any complication (ARD, 2.20%; 95% CI, 0.79-3.62; P = .002) and major complications (ARD, 1.63%; 95% CI, 0.31-2.95; P = .02).

Among the full cohort eligible for matching, the association between smoking and complications was consistently observed (eTable 8 in the Supplement). The risk of postprocedural complications also increased with the magnitude of the smoking exposure timeframe (eTable 9 in the Supplement). Compared with active smokers (n = 5173; smoking within 2 weeks before the procedure), the risk of any complication was decreased by 65% for never smokers (n = 1197; adjusted odds ratio, 0.45; 95% CI, 0.34-0.59) and 29% for former smokers (n = 4755; adjusted odds ratio, 0.71; 95% CI, 0.61-0.83; P = .001 for interaction), which differed across intervention types (Figure 3).

Discussion

Our large, contemporary study of 14 350 cases evaluated the association of preprocedural smoking with early postprocedural outcomes following revascularization for IC. We confirmed a high rate of smoking in patients undergoing elective revascularization. In this well-balanced propensity score–matched cohort, smoking was associated with a 48% relative increase in the risk of any 30-day postprocedural complication compared with nonsmokers (ARD, 3.68%; 95% CI, 2.31-5.06). All smokers undergoing revascularization, regardless of intervention modality and anatomic level of disease, had a higher risk of early postprocedural complications. This risk fell by 29% among former smokers (adjusted odds ratio, 0.71; 95% CI, 0.61-0.83) with more than 1 year of smoking cessation and by 65% among never smokers (adjusted odds ratio, 0.45; 95% CI, 0.34-0.59). Our findings were robust to adjustments for potential confounders, including patient comorbidity, frailty, healthy user indicators, health care access inequalities with investigation by multiple methods, across subgroups, and in sensitivity analysis.

A large body of evidence has established that cigarette smoking is a key modifiable risk factor in the earlier onset of arterial changes contributing to the pathogenesis of atherosclerotic CVD, including PAD.1-3,7-10,12-14 Over the past several decades, the national smoking rate has decreased.42 In conjunction with new, effective therapies and increasing rates of other OMT, CVD-related mortality has declined. Despite clear and consistent evidence-based guidelines promoting smoking cessation,17 patients with PAD repeatedly demonstrate higher rates of smoking compared with those with other CVD.15,19 In the Reduction of Atherothrombosis for Continued Health (REACH) registry,43 patients with isolated PAD smoked at twice the rate of patients with other CVD. In the Patient‐Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) registry,17 more than 30% of patients evaluated for IC were smokers but only 25% were referred to smoking cessation counseling or received assistive pharmacotherapy. Observational data suggest less than 25% of patients with IC achieve OMT prior to elective open revascularization.18,19 Our data reinforce these findings. More than half the patients smoked within 1 year of an elective intervention, and the smoking rate was lower among those with other concurrent CVD. In contrast to declining rates of smoking nationally, the proportion of smoking veterans remained strikingly unchanged throughout our 9-year study period. The alarmingly high and stable rate of smokers undergoing revascularization for IC may be because of both the causal relationship between smoking and PAD and an underappreciation of the benefits of smoking cessation for patients with PAD. Further, the barriers to revascularization are lower with endovascular approaches such that surgeons and interventionalists may proceed with revascularization without fully achieving OMT.

Early postprocedural complications decrease patient satisfaction and increase hospital length of stay, readmission, and health care costs.44 Our data support a large body of cross-discipline evidence demonstrating increased early postoperative complications, especially respiratory and wound-related events, for smokers following a variety of procedures.45-47 We observed the risk of any complication for smokers was higher among those with COPD, as expected, and among patients from racial and ethnic minority groups, mirroring ubiquitously observed health care disparities.48,49 Nonfrail patients also demonstrated an increased relative risk of any complication associated with smoking compared with frail patients. As observed across diverse and PAD-specific procedures,25,50-52 surgeons and interventionalists may apply more rigorous patient selection and preprocedural optimization (eg, prehabilitation, nutritional support) for frail patients undergoing physiologically stressful procedures.24,25,27,41 We therefore hypothesize that these mitigation efforts may exceed the relative risk reduction achieved with smoking cessation. In contrast, robust patients may be subject to less selection scrutiny and preprocedural optimization. This is supported by the relative increase in any postprocedural complication associated with smoking in nonfrail patients. Alternatively, the depleted physiologic reserve of frailty increases the risk of decompensation in response to a physiologic stressor (ie, procedure) so strongly that it may dominate the effect of smoking (eg, among frail patients, the reserve is so greatly reduced such that the effects of smoking are blunted).

Prior work demonstrated that early postprocedural morbidity and mortality are associated with both the physiologic stress of the intervention25,53 and smoking status.6,8-10 As previously observed among smokers,53 complications were more common after hybrid revascularization (204 [17.3%]) and open revascularization (228 [15.4%]) than endovascular revascularization (26 [4.3%]). We extend prior findings in 2 important ways. First, smoking was associated with a 48% increase in any complication overall (Table 2) that was not limited to high-stress open interventions but was observed across all modalities. Among patients undergoing endovascular revascularization, smoking was associated with a 2% absolute risk (ARD, 2.19%; 95% CI, 0.77-3.60) and 100% relative risk (Table 1) increase in any complication. Second, smoking was associated with an increased risk of early vascular graft failure following a broad range of open revascularization procedures performed exclusively to treat IC. Therefore, regardless of the associated surgical stress or the perceived risk of the intervention, smoking conferred an elevated risk of postprocedural complications.

Evidence-based societal guidelines reflect the uncertain effectiveness, lack of durability, and inability to impact CVD risks attributed to revascularization for IC. In 2015, the Society of Vascular Surgery endorsed a Grade 1B recommendation for revascularization following OMT only for ongoing “significant functional or lifestyle-limiting disabilities.”13 Similarly, in the 2018 American College of Cardiology/American Heart Association Appropriate Use Criteria, endovascular or open revascularization was deemed to be appropriate or may be appropriate for aortoiliac, superficial femoral, and popliteal artery disease only following OMT.14 Smoking cessation, a significant focus of OMT, is an important modifiable risk factor. Following smoking cessation, a slow decline in CVD risk is observed over decades.54 Our data support these findings, demonstrating no risk reduction in the early postprocedural rate of neurologic or cardiovascular complications. However, smoking within 1 year of a procedure was associated with an increase in early postprocedural complications. Although our data did not permit direct testing of PAD-specific smoking cessation, we did confirm the benefits of more than 1 year of smoking cessation with a 29% reduction in early postprocedural complications (adjusted OR, 0.71; 95% CI, 0.61-0.83). Surprisingly, the largest relative risk reduction occurred in those undergoing endovascular interventions. Our data highlight the persistently and unacceptably high rate of smoking in patients with IC and the significant risk associated with smoking on revascularization outcomes across all modalities and strongly suggest patients should receive comprehensive smoking cessation counseling prior to revascularization (including endovascular modalities). Further investigation is required to understand the duration of smoking cessation required to minimize the risks of early postprocedural complications, long-term CVD morbidity and mortality, and maximize functional outcomes.

Limitations

Our investigation has limitations. First, VASQIP data are abstracted from billing information and medical records reviewed in full by trained nurse reviewers and are at risk of measurement error. A specific set of data are abstracted, and the prescription status for lipid lowering, antiplatelet, and antithrombotic therapies, plaque morphology, and postprocedural outcomes beyond 30 days are not captured. However, in sensitivity analyses, the E-value suggests unmeasured confounding is unlikely to explain the entirety of the observed association. Second, smoking status is mainly self-reported, which may result in misclassification. Third, because our data could not discern if smoking cessation was a part of PAD-related OMT, smoking status may be a surrogate indicator of other healthy behaviors (eg, cessation may represent patient compliance). Fourth, smoking increases the onset and may alter the underlying pathophysiology of comorbid conditions. These factors are captured in the differences among those who did and did not match, possibly limiting the generalization of our matched analysis. However, multivariable modeling of the full cohort eligible for matching demonstrated similar point estimates, suggesting accuracy. Fifth, the VASQIP provides a representative yet incomplete sample of all surgical procedures, with an unquantified portion of interventions not captured. Therefore, the yearly incidence of procedures for IC cannot be fully quantified.55 Sixth, the associations between smoking, sex, and postprocedural complications cannot be adequately assessed in the dominantly male VASQIP sample.

Conclusions

In this cohort study, following elective open and endovascular revascularization for IC, smoking was associated with an increased risk of any and respiratory-specific early postprocedural complications. Further, smoking within 1 year of a procedure was associated with an increase in complications, especially for endovascular interventions. Our findings support the strong societal guidelines emphasizing OMT and call for using comprehensive OMT programs that include smoking cessation therapies prior to revascularization for IC to reduce both early postprocedural complications and long-term CVD morbidity and mortality.

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Article Information

Accepted for Publication: August 4, 2021.

Published Online: October 6, 2021. doi:10.1001/jamacardio.2021.3979

Corresponding Author: Edith Tzeng, MD, Division of Vascular Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St, South Tower, Room 351.6, Pittsburgh, PA 15213 (tzenge@upmc.edu).

Author Contributions: Drs Reitz and Tzeng had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Hall and Tzeng are co–senior authors.

Study concept and design: Reitz, Meyer, Arya, Goodney, Hall, Tzeng.

Acquisition, analysis, or interpretation of data: Reitz, Althouse, Meyer, Shireman, Hall.

Drafting of the manuscript: Reitz, Meyer.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Reitz, Meyer, Goodney.

Obtained funding: Tzeng.

Administrative, technical, or material support: Reitz, Arya, Tzeng.

Study supervision: Arya, Hall, Tzeng.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was supported in part by grants I21 HX-002345 and XVA 72-909 from the Veterans Health Administration Office of Research and Development (Dr Hall); grant U01 TR002393 from the National Center for Advancing Translational Sciences (Drs Hall and Shireman); grant T32 HL0098036 from the National Heart, Lung, and Blood Institute (Dr Reitz); and grant L30 AG064730 from the National Institute on Aging (Dr Reitz).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The opinions expressed here are those of the authors and do not necessarily reflect the position of the US Department of Veterans Affairs or the US government.

Meeting Presentation: A subset of these data were presented virtually at the VA Pittsburgh Health Care System Research Week; May 17, 2021.

Additional Contributions: We thank the US Department of Veterans Affairs Office of Rural Health for sharing with us the use of their Rurality Calculator, developed by Daniel Palmeri, BS.

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