Lung Function Impairment Is Related to Subclinical Atherosclerosis Only in Active Smokers
by
, , , and
Jessica González
1,2,3,4, 
Esther Gracia-Lavedan
2,3,4,
Silvia Gómez
1,2,3,
Silvia Barril
1,2,3,
Pere Godoy
3,5,6,
Marcelino Bermúdez-López
3,7,
Angels Betriu
3,7,
Elvira Fernández
3,7,
Albert Lecube
8,9
,
Reinald Pamplona
3,10,
Francisco Purroy
3,11, 
Cristina Farràs
12,
Ferran Barbé
1,2,3,4,
Gerard Torres
2,3,4,13,
Jordi de Batlle
2,3,4,* and
on behalf of the ILERVAS Project Collaborators
† 1
Respiratory Department, Hospital Universitari Arnau de Vilanova and Santa Maria, 25198 Lleida, Spain
2
Translational Research in Respiratory Medicine Group (TRRM), 25198 Lleida, Spain
3
Lleida Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain
4
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
5
Health Department, Public Health Agency of Catalonia, 25006 Lleida, Spain
6
CIBER de Epidemiología y Salud Publica, Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
7
Grupo Investigación Translacional Vascular y Renal, IRBLleida, Red de Investigación Renal (RedInRen. ISCIII), 25198 Lleida, Spain
8
Endocrinology and Nutrition Department, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain
9
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
10
Experimental Medicine Department, Universitat de Lleida, 25198 Lleida, Spain
11
Stroke Unit, Hospital Universitari Arnau de Vilanova, Clinical Neurosciencies Group, IRBLleida, UdL, 25198 Lleida, Spain
12
Catalain Institute of Health (ICS), Área Básica de Salut Borges Blanques, 25400 Lleida, Spain
13
Internal Medicina Department, Hospital de Santa María, IRB Lleida, 25198 Lleida, Spain
*
Author to whom correspondence should be addressed.
†
Collaborators of the ILERVAS Project names are provided in the acknowledgments.
J. Vasc. Dis. 2022, 1(1), 24-35; https://doi.org/10.3390/jvd1010004
Submission received: 27 June 2022
/
Revised: 19 July 2022
/
Accepted: 3 August 2022
/
Published: 5 August 2022
(This article belongs to the Special Issue Current Advances, Challenges, and Molecular Insight into Subclinical Atherosclerosis)
Abstract
:Background: Although an association between lung function and subclinical atherosclerosis has been reported, it remains unclear whether this association is only driven by tobacco smoking. We aimed to assess this in a population with at least one cardiovascular risk factor. Methods: We recruited 6209 subjects aged between 45 and 70 years with at least one cardiovascular risk factor (excluding diabetes mellitus) participating in the ILERVAS project 2015–2018. Lung function was determined by spirometry. Subclinical atherosclerosis was assessed with the ankle–brachial index (ABI) and the presence of carotid and femoral plaques measured by ultrasound. Results: A total of 5927 subjects were included: 49% male, median (p25–p75) age 57 years (52–62). Plaques were found in 4337 (73.2%) of the subjects. The patients with atherosclerosis showed worse lung function: median forced expiratory volume in one second (FEV1) 95% and forced vital capacity (FVC) 94% in the patients with plaques vs. 99% and 98% in the other patients (p < 0.001). Adjusted models stratified by smoking status showed that being in the lower quartiles of FEV1 % was associated with carotid and femoral plaques (OR 1.599, p = 0.005; and OR 1.654, p = 0.006), whereas FVC % was inversely associated with carotid plaques (OR 0.967, p = 0.041). A pathological ABI was associated with worse FEV1 (OR 1.971, p = 0.038) and the presence of airway obstruction (OR 1.658, p = 0.015). However, these differences were restricted to current smokers. Conclusions: Lung function impairment was correlated with subclinical atherosclerosis only in current smokers. This highlights the unique role of smoking-related vascular and pulmonary dysfunction in early stages of pulmonary and cardiovascular afflictions.
1. Introduction
Impaired lung function, represented by the forced expiratory volume in one second (FEV1) or forced vital capacity (FVC), is related to an increased incidence of and mortality from cardiovascular disease (CVD) and all-cause mortality [1,2,3,4,5,6,7]. The mechanisms underlying this relationship are uncertain, and, given the association among the never smokers [1,8,9], it is unlikely that tobacco smoking could be the only responsible factor. Most studies attempting to understand this relationship have focused on the clinical outcomes. However, subclinical atherosclerosis is a well-established risk factor for ischemic CVD. Numerous large cohorts with long follow-up periods have shown a clear association between the presence of subclinical atheromatous plaques in the carotid arteries and the risk of a coronary or cerebrovascular event [10,11,12].
The measurement of subclinical atherosclerosis offers a distinct approach to assessing the underlying mechanisms linking lung dysfunction and CVDs. The literature regarding the relationship between subclinical atherosclerosis and lung function is not limited [13,14,15,16,17,18,19,20], but shows inconsistent results. Some of the studies have found an inverse correlation between lung function and subclinical atherosclerosis [13,14,20], but not others [15,18,19,21]. Although the differences exist in the characteristics of the studied populations and the tools used to assess subclinical atherosclerosis, the key factors explaining the conflicting results may be the matching for potential confounding variables and, most importantly, the inclusion of a never smoker control group. Therefore, given the overlapping mechanisms linking tobacco, lung function and subclinical atherosclerosis, this relationship must be studied in a large cohort of well-characterized subjects, including the never smokers.
The current study aimed to clarify the relationship between lung function impairment and subclinical carotid and femoral atherosclerosis, as measured by the ankle–brachial index (ABI) and the ultrasound-confirmed presence of carotid and femoral plaques, in a population of subjects with at least one cardiovascular risk factor.
2. Material and Methods
2.1. Study Population
This is an ancillary study of the ILERVAS project (clinicaltrials.gov identifier: NCT03228459), approved by the Ethics and Clinical Research Committee of the University Hospital Arnau de Vilanova de Lleida, 2 June 2015. ILERVAS is a randomized interventional study aiming, among other objectives, to assess the impact of the early diagnosis of atherosclerosis on cardiovascular morbidity and mortality and to detect potential biomarkers that could improve the cardiovascular risk predictions. The ILERVAS intervention group (subjects participating in the early diagnosis program) comprises 8330 subjects aged between 45 and 65 years (men) or 50 and 70 years (women) with the following characteristics: at least one CVD risk factor (hypertension, dyslipidemia, obesity, smoking habit, or first-degree family history of early CVD); no prior medical history of CVD (angina, myocardial infarction, stroke, peripheral arterial disease, intestinal ischemia, or carotid surgery), diabetes, chronic kidney disease or active neoplasm; not institutionalized or receiving long-term home care; and a life expectancy greater than or equal to 18 months. The current study focused on 6209 consecutive subjects who completed lung function tests (spirometry). All of the participants were recruited in the province of Lleida (Catalonia, Spain) between 2015 and 2018. The ILERVAS protocol and study design are described elsewhere [22]. The project was approved by the ethics committee of the University Hospital Arnau de Vilanova with code CEIC-1410.
2.2. Clinical and Demographic Data
At the baseline, some of the sociodemographic data were collected from an electronic database (Information System for the Development of Research in Primary Care, SIDIAP) [23]. Important information, such as age, sex, weight, height, waist circumference, body mass index (BMI), office blood pressure and tobacco habits (active smoker, former smoker (at least one month without tobacco) or never smoker; total pack-years) was collected in the face-to-face interview and physical examination on the ILERVAS bus.
2.3. Biochemical Measures
Using dried capillary blood testing (fingertip puncture) and the REFLOTRON® Plus system (Roche), the creatinine (mg/dl) and total cholesterol (mg/dl) levels were obtained. The subjects with a total cholesterol greater than 200 mg/dl after 6 h of fasting or when the total cholesterol was ≥250 mg/dL regardless of the fasting hours were considered eligible to perform the complete lipid profile determinations: HDL cholesterol; LDL cholesterol and triglycerides. Additionally, the glycated hemoglobin (HbA1c) level was analyzed using the same system. Prediabetes was diagnosed if the value of the glycated hemoglobin was between 5.7% and 6.4%. Based on the creatinine levels and considering ethnicity and sex, the CKD-EPI glomerular filtration rate of each subject was determined [24].
2.4. Carotid Ultrasound
Ultrasound imaging was performed on both the carotid (common artery, bifurcation, internal and external) and femoral (common and superficial) arteries. The images were obtained by trained sonographers, using the Doppler Ultrasound Vivid-I (General Electric Healthcare, Waukesha, WI, USA) equipped with a linear-transducer broadband linear 12 L-RS that operates at frequencies between 6 and 13 MHz [22]. Standardized and validated scanning and reading protocols were used to decrease inter-operator variability and type 2 errors [25]. Intra-observer reliability assessment showed a k-coefficient of one, with two repeated measurements and 1007 observations. The overall inter-rater reliability for all of the raters showed a k-coefficient of 0.915 (95% CI: 0.892–0.944; 959 observations), demonstrating excellent reliability. The readers were unaware of the patients’ clinical histories.
2.5. Lung Function
To assess lung function, forced spirometry was performed using a portable ultrasonic spirometer (Datospir©; Sibelmed, Barcelona, Spain). The pulmonary function tests were performed by trained and certified pulmonary experts, following the guidelines of the Spanish Respiratory Society (SEPAR) [28]. Using this test, the forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and the ratio between FEV1 and FVC (FEV1/FVC) were measured in ml and expressed as percentages of the predicted values [29]. A bronchodilator test was not included in the pulmonary evaluation. Airway obstruction (AO) was defined as an FEV1/FVC < 70%, using the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [30].
2.6. Ankle-Brachial Index (ABI)
The ABI, defined as the ratio of the ankle to arm systolic blood pressure, is commonly used to assess lower extremity arterial disease in clinical practice and epidemiologic studies [31]. The ABI was measured using a continuous Doppler (Hadecco ES100X MiniDop), sphygmomanometer and blood pressure cuffs (Riester minimus III). The systolic blood pressure was measured in the brachial artery, posterior tibial artery and dorsalis pedis artery in both limbs in the prone position. The ratios between the tibial and pedal systolic blood pressure in each leg and higher brachial blood pressure were calculated. The final value for each limb was the lower value of those obtained between the tibial and pedal blood pressure. An ankle–brachial index value ≤0.9 suggested stenosis and was classified as pathologic. The values greater than 1.4 were excluded and suggested arterial rigidity or calcified arterial walls [22].
2.7. Statistical Analysis
A descriptive analysis of the participants’ characteristics was performed for the presence/absence of atheromatous plaques. The categorical variables were described using percentages, and the continuous variables were described using medians and the 25th and 75th percentiles. Chi-squared test and the Wilcoxon rank-sum test were used to evaluate the differences for the categorical and continuous variables, respectively. The association of lung function with the presence of carotid plaques, femoral plaques and pathologic ABI was evaluated, using multivariate unconditional logistic regression models. The models were adjusted for the following important risk factors: sex, age, blood pressure, cholesterol, BMI, waist circumference, smoking habit, pack-years, prediabetes, hypertension and hypolipidemic treatment. An analysis was also performed after stratifying by smoking habit (never, former and current smokers). Finally, as a supplemental analysis, the impact of smoking cessation on lung function was assessed, using multivariate linear regression models. The statistical analyses were conducted using R: A language and environment for statistical computing, version 3.6 (R Core Team, 2019, Vienna, Austria).
3. Results
Among the 6209 consecutive subjects with available lung function, we excluded 33 subjects with missing, invalid or nonreproducible data; 96 subjects diagnosed with diabetes; and, 153 with renal failure (eGFR (estimated glomerular) filtration rate of <60% mL/min/1.73 m2). Finally, 5927 subjects were included in the analyses.
The characteristics of the study population according to the presence of the atheromatous plaques are displayed in Table 1. Briefly, the participants had a median (p25–p75) age of 57 (52–62) years and a median BMI of 28.4 (25.5–31.6) kg/m2. Sex was distributed equally (50.6% female and 49.4% male). The patients with atheromatous plaques were more likely to be the current smokers (33.5%), with twice as much accumulated exposure to tobacco (23.5 vs. 12.8 pack-years). The cardiovascular risk factors were more prevalent in the patients with plaques, including higher levels of cholesterol, triglycerides, systolic pressure and diastolic pressure. The patients with plaques showed higher proportions of antihypertensive drug use (33.2% vs. 27.7%) and pathological ABI (6.36% vs. 3.99%) and worse lung function as defined by FEV1 % (95% vs. 99%) and FVC % (94% vs. 98%).
Table 2 shows the prevalence of the atheromatous plaques and pathological ABI according to lung function in the never smokers, former smokers and current smokers. Overall, the prevalence of subclinical atherosclerosis was higher among the patients with worse lung function, as represented by the quartiles of FEV1 and FVC impairment. Although the current smoker participants with worse lung function showed a higher prevalence of carotid and femoral plaques (prevalence of carotid plaques: Q1 vs. Q4 FEV1: 48% vs. 65%, p <0.001; prevalence of femoral plaques: Q1 vs. Q4 FEV1: 57% vs. 79%, p < 0.001), in the former smokers, this relationship held only for the carotid plaques (prevalence of carotid plaques: Q1 vs. Q4 FEV1: 48% vs. 61%, p < 0.001; prevalence of femoral plaques: Q1 vs. Q4 FEV1: 54% vs. 63%, p = 0.050) and was almost nonexistent among the never smokers (prevalence of carotid plaques: Q1 vs. Q4 FEV1: 46% vs. 53%, p = 0.047; prevalence of femoral plaques: Q1 vs. Q4 FEV1: 41% vs. 42%, p = 0.811). When considering ABI, statistically significant differences were only found in the current smoker group.
Only the presence of airway obstruction (OR: 1.23, p = 0.015) and being in the worse quartiles of FEV1 % (Q3 OR: 1.17, p = 0.048; and Q4 OR: 1.27, p < 0.004) were associated with the presence of carotid plaques after adjustment (Table 3). By contrast, an impaired FVC (<80%) was not associated with subclinical carotid atherosclerosis. No significant associations were found between the lung function and femoral plaques. Finally, being in the worse quartile of FEV1 % (OR: 1.43, CI 1.00–2.04, p = 0.046) and having airway obstruction (OR: 1.54, CI 1.15–2.05, p = 0.004) were associated with having pathological ABI.
Table 4 shows the adjusted logistic regression models for the relationship between lung function and the presence of carotid plaques, femoral plaques and pathologic ABI, stratified by the smoking status. In the current smokers, both FEV1 % and FVC % were associated with carotid plaques and pathological ABI, while only FEV1 % was associated with femoral plaques. By contrast, the association between the AO and femoral plaques was only found in the former smokers, and no associations were found in the never smokers.
Finally, as a supplemental analysis, Table 5 explores the impact of smoking cessation on lung function, showing that the current smokers have significantly worse lung function than the former smokers.
4. Discussions
Our main finding is that in the subjects with at least one cardiovascular risk factor, lung function impairment expressed as a lower FEV1, even in the normal range, is correlated with subclinical atherosclerosis, but only in the current smokers. These findings highlight the critical role of smoking in the relationship between lung function and subclinical atherosclerosis.
The relationship between lung function and subclinical atherosclerosis has been analyzed in various epidemiological cohorts [13,14,15,16,17,18,19,20]. Based on the data from the British Regional Heart Study, Ebrahim et al. [15] reported a significant age-adjusted association between FEV1 and carotid intima-media thickness (IMT) in 800 subjects. However, they did not adjust for smoking status, cholesterol, hypertension or other important variables. More recently, a close association was revealed between subclinical atherosclerosis (including the ABI) and pulmonary function (FEV1 % and FVC %) in 3775 middle-aged smokers at risk of early atherosclerosis [20]. Additionally, the study of a prospective cohort of 656 volunteers aged 50–71 years found that reduced peak expiratory flow (PEF) was related to the development of carotid plaques after adjustment [14]. Thus, our results agree with this previous study, but extend the findings by considering the population of the never smokers. Furthermore, the inclusion of additional potential confounding variables not assessed in some previous studies (such as waist circumference, prediabetes and the use of hypertensive or hypolipidemic drugs) contributes to the appropriateness of the current research.
Given the potentially strong confounding by tobacco use in the relationship between lung function and subclinical atherosclerosis, an adjustment by tobacco use was insufficient to control for this factor, and a substantial degree of residual confounding could not be disregarded. Therefore, exploring the relationship stratified by smoking status was performed, including the never smokers. The first study to explore this issue [19], comprising 14,000 subjects with 54% of the never smokers, showed that the existing association between both the IMT and the ABI and FEV1 was attenuated after adjustment for the CVD risk factors and disappeared in the group of the never smokers. Regarding the presence of carotid plaques, a small association was observed with lung function that again disappeared in the never smokers. Our results agree with those findings and provide added information concerning femoral plaques, with a significant relationship between the worse quartiles of FEV1 and the presence of both carotid and femoral plaques, although only in the current smokers. Moreover, the reported differences in lung function after smoking cessation (regardless of potential biases related with the cause of smoking cessation) combined with the finding of lung function impairment being associated with subclinical atherosclerosis only in the current smokers, highlights the public health relevance of promoting smoking cessation.
In our study, the patients with worse lung function (represented by the quartiles of FEV1 and FVC impairment), presented a higher prevalence of subclinical atherosclerosis. Several existing hypotheses can explain the association between impaired lung function and cardiovascular health [8], including the role of the lungs in the capture and elimination of external toxic agents [32,33], ventilation/perfusion mismatch associated with impaired lung function [8], a systemic inflammatory response [34,35] and oxidative stress [36]. However, regarding the results of the present study, the cause of lung function impairment and its specific inflammatory mechanisms may be the determinant of the subclinical atherosclerosis in the ultrasound examinations. In other words, only the lung function impairment mediated by active tobacco exposure can explain the presence of the subclinical atherosclerosis. This finding may be that cigarette smoking is one of the strongest sources of oxidative stress and inflammatory products, causing both vascular and pulmonary damage [37,38].
The current study has several strengths that should be disclosed. The large number of middle-aged subjects included, combined with their cardiovascular risk profile, makes our study population well suited for answering the research questions posed in the manuscript. Additionally, the subclinical atherosclerosis was assessed by experienced personnel using ultrasound and covering key arterial territories. Finally, the inclusion of a significant proportion of never smokers was paramount. Several potential limitations should also be considered. First, additional information on the cardiovascular factors would have been helpful (e.g., the time since hypertension or dyslipidemia diagnostics and its degree of control with medications). However, their inclusion in the analysis would not have significantly affected the results, because the already large number of cardiovascular-risk-related variables used in the adjusted models should suffice for the appropriate control of confounding. Next, the lack of postbronchodilator spirometry precluded the characterization of the airway hyper-responsiveness of the included COPD patients. This information would be valuable, given the potential differences in the inflammatory profiles of the patients and the relationship of these profiles with the formation of atheromatous plaques. Next, our study population was based in a rural area, implying low exposure to air pollution and its reported airway effects. However, this limitation could also be seen as a strength, because the rural areas are frequently under-represented in research studies. Finally, a more precise characterization of the participants, including genetic profiling, measures of arterial stiffness (Pulse Wave Velocity) or oxidized LDL receptor could have provided more insight on the potential mechanisms behind the reported associations.
5. Conclusions
In conclusion, the finding of a relationship between lung function (represented by FEV1) and subclinical carotid and femoral atherosclerosis only in the current smokers suggests that the lung function could be used to measure the cardiovascular health status of such individuals. Thus, we recommend performing spirometry testing in all of the smoking patients and providing them with smoking cessation advice to improve both pulmonary and cardiovascular health.
Author Contributions
Conceptualization, J.G., F.B., G.T. and J.d.B.; methodology, J.G., F.B., G.T. and J.d.B.; formal analysis, E.G.-L.; investigation, all authors; writing—original draft preparation, J.G. and J.d.B.; writing—review and editing, all authors. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by grants from the Diputació de Lleida, Instituto de Salud Carlos III (Action Plan II14//00008; RETIC RD16/0009/0011), Ministerio de Ciencia, Innovación y Universidades (IJC2018-037792-I), Fundación de la Sociedad Española de Endocrinología y Nutrición (FSEEN), Esteve Laboratory, Generalitat of Catalonia (Agency for Management of University and Research Grants: 2017SGR696, and Department of Health: SLT0021600250), IRBLleida Biobank (B.0000682) and Plataforma Biobancos PT13/0010/0014. Jordi de Batlle has received financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), cofunded by the European Social Fund (ESF), “Investing in your future”. CIBER de Diabetes y Enfermedades Metabólicas Asociadas and CIBER de Enfermedades Respiratorias are initiatives of the Instituto de Salud Carlos III. This study was cofunded by FEDER funds from the European Union (“A way to build Europe”). IRBLleida is a CERCA Programme/Generalitat of Catalonia. Funding agencies were not involved in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of University Hospital Arnau de Vilanova (protocol code CEIC-1410, 19 December 2014).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
Acknowledgments
ILERVAS Project collaborators: Eva Castro-Boqué, José Manuel Valdivielso, Dídac Mauricio, Montse Martínez-Alonso, Eva Miquel, Marta Ortega, Manuel Sánchez-de-la-Torre, Manuel Portero-Otín, Mariona Jové, Enrique Sánchez, Marta Hernández, Ferran Rius, Josep Franch-Nadal, Esmeralda Castelblanco, Glòria Arqué, Ana Vena Martínez.
Conflicts of Interest
The authors declare no conflict of interest.
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Table 1.
Study population: clinical and demographic data based on the presence of atheromatous plaques.
Table 1.
Study population: clinical and demographic data based on the presence of atheromatous plaques.
| Variables | Presence of Atheromatous Plaques | |||
|---|---|---|---|---|
| ALL n = 5927 | No Plaques n = 1590 | Plaques n = 4337 | p Value a | |
| Age, years, median (p25;p75) | 57.0 (52.0;62.0) | 55.0 (51.0;60.0) | 58.0 (53.0;63.0) | <0.001 |
| Gender, Male, n (%) | 2928 (49.4) | 569 (35.7) | 2359 (54.4) | <0.001 |
| BMI, kg/m2, median (p25;p75) | 28.4 (25.5;31.6) | 28.4 (25.3;31.7) | 28.4 (25.5;31.6) | 0.974 |
| Waist circumference, n (%) | 0.003 | |||
| Male <102 cm; Female <88 cm | 1861 (31.4) | 451 (28.4) | 1410 (32.5) | |
| Male ≥102 cm; Female ≥88 cm | 4065 (68.6) | 1139 (71.6) | 2926 (67.5%) | |
| Smoking history, n (%) | <0.001 | |||
| Never Smoker | 2215 (37.4) | 767 (48.2) | 1448 (33.4) | |
| Current | 1760 (29.7) | 308 (19.4) | 1452 (33.5) | |
| Former | 1952 (32.9) | 515 (32.4) | 1437 (33.1) | |
| Pack-years of smoking, median (p25;p75) | 20.8 (10.3;33.5) | 12.8 (5.6;22.5) | 23.5 (12.3;35.0) | <0.001 |
| Cholesterol, mg/dl, median (p25;p75) | 203 (180;229) | 200 (178;227) | 203 (181;230) | 0.013 |
| Cholesterol | 0.006 | |||
| <200 mg/dl | 2754 (46.5) | 785 (49.4) | 1969 (45.4) | |
| ≥200 mg/dl | 3173 (53.5) | 805 (50.6) | 2368 (54.6) | |
| LDL *, mg/dl, median (p25;p75) | 142 (127;159) | 140 (126;157) | 143 (128;159) | 0.062 |
| HDL *, mg/dl, median (p25;p75) | 55.0 (46.0;66.0) | 57.5 (49.0;68.0) | 54.0 (46.0;66.0) | <0.001 |
| Triglycerides, mg/dl, median (p25;p75) | 132 (100;178) | 123 (94.0;167) | 135 (101;183) | <0.001 |
| Systolic blood pressure, mmHg, median (p25;p75) | 131 (120;142) | 127 (117;138) | 132 (121;144) | <0.001 |
| Diastolic blood pressure, mmHg, median (p25;p75) | 82.0 (75.7;88.0) | 80.0 (74.0;87.0) | 82.0 (76.0;88.7) | <0.001 |
| Hypolipidemic treatment, n (%) | 1001 (16.9) | 212 (13.3) | 789 (18.2) | <0.001 |
| Antihypertensive treatment, n (%) | 1882 (31.8) | 440 (27.7) | 1442 (33.2) | <0.001 |
| FEV1 %, median (p25;p75) | 96.0 (84.0;108) | 99.0 (88.0;111) | 95.0 (83.0;106) | <0.001 |
| FVC %, median (p25;p75) | 95.0 (84.0;106) | 98.0 (87.0;109) | 94.0 (84.0;105) | <0.001 |
| ABI PTA pathologic, n (%) | 337 (5.72%) | 63 (3.99%) | 274 (6.36%) | 0.001 |
Median (25th percentile; 75th percentile) a Wilcoxon rank-sum test for continuous variables and Pearson’s chi-squared test for categorical variables. * Lipid profile only available for participants with total cholesterol higher than 200 mg/dL. FEV1 % = forced expiratory volume-one second percentage; FVC % = forced vital capacity percentage; BMI = body mass index; LDL = low-density lipoprotein cholesterol; HDL = high-density lipoprotein cholesterol; ABI PTA = ankle–brachial index posterior tibial artery.
Table 2.
Prevalence of carotid/femoral atheromatous plaques and pathologic ABI in relation to tobacco consumption and lung function.
Table 2.
Prevalence of carotid/femoral atheromatous plaques and pathologic ABI in relation to tobacco consumption and lung function.
| Variables | Presence of CAROTID Plaque | |||||||
| ALL | p Value | Never Smokers | p Value | Former Smokers | p Value | Current Smokers | p Value | |
| n = 5927 | n = 2215 | n = 1952 | n = 1760 | |||||
| FEV1 %, quartiles | ||||||||
| 108–157 | 649/1383 (47%) | <0.001 | 297/650 (46%) | 0.047 | 218/452 (48%) | <0.001 | 134/281 (48%) | <0.001 |
| 96–108 | 747/1488 (50%) | 311/621 (50%) | 231/478 (48%) | 205/389 (53%) | ||||
| 84–96 | 823/1524 (54%) | 273/519 (53%) | 272/518 (53%) | 278/487 (57%) | ||||
| 22–84 | 920/1532 (60%) | 226/425 (53%) | 305/504 (61%) | 389/603 (65%) | ||||
| FVC % ≥80% | 2563/4968 (52%) | <0.001 | 928/1880 (49%) | 0.189 | 833/1643 (51%) | <0.001 | 802/1445 (56%) | 0.003 |
| <80% | 576/959 (60%) | 179/335 (53%) | 193/309 (62%) | 204/315 (65%) | ||||
| FEV1/FVC ≥70% | 2636/5129 (51%) | <0.001 | 996/2026 (49%) | 0.015 | 869/1707 (51%) | <0.001 | 771/1396 (55%) | 0.002 |
| <70% | 503/798 (63%) | 111/189 (59%) | 157/245 (64%) | 235/364 (65%) | ||||
| Variables | Presence of FEMORAL Plaque | |||||||
| ALL | p Value | Never Smokers | p Value | Former Smokers | p Value | Current Smokers | p Value | |
| n = 5927 | n = 2215 | n = 1952 | n = 1760 | |||||
| FEV1 %, quartiles | ||||||||
| 108–157 | 672/1383 (49%) | <0.001 | 267/650 (41%) | 0.811 | 244/452 (54%) | 0.05 | 161/281 (57%) | <0.001 |
| 96–108 | 788/1488 (53%) | 248/621 (40%) | 278/478 (58%) | 262/389 (67%) | ||||
| 84–96 | 889/1524 (58%) | 221/519 (43%) | 310/518 (60%) | 358/487 (74%) | ||||
| 22–84 | 969/1532 (63%) | 179/425 (42%) | 316/504 (63%) | 474/603 (79%) | ||||
| FVC % ≥80% | 2735/4968 (55%) | 0.001 | 779/1880 (41%) | 0.82 | 953/1643 (58%) | 0.108 | 1003/1445 (69%) | <0.001 |
| <80% | 583/959 (61%) | 136/335 (41%) | 195/309 (63%) | 252/315 (80%) | ||||
| FEV1/FVC ≥70% | 2776/5129 (54%) | <0.001 | 829/2026 (41%) | 0.251 | 983/1707 (58%) | 0.005 | 964/1396 (69%) | <0.001 |
| <70% | 542/798 (68%) | 86/189 (46%) | 165/245 (67%) | 291/364 (80%) | ||||
| Variables | Pathologic ABI | |||||||
| ALL | p Value | Never Smokers | p Value | Former Smokers | p Value | Current Smokers | p Value | |
| n = 5887 | n = 2195 | n = 1938 | n = 1754 | |||||
| FEV1 %, quartiles | ||||||||
| 108–157 | 57/1375 (4%) | <0.001 | 29/648 (4%) | 0.933 | 13/447 (3%) | 0.318 | 15/280 (5%) | 0.002 |
| 96–108 | 75/1475 (5%) | 31/613 (5%) | 21/473 (4%) | 23/389 (6%) | ||||
| 84–96 | 88/1515 (6%) | 22/513 (4%) | 23/515 (4%) | 43/487 (9%) | ||||
| 22–84 | 117/1522 (8%) | 20/421 (5%) | 27/503 (5%) | 70/598 (12%) | ||||
| FVC % ≥80% | 275/4936 (6%) | 0.282 | 92/1864 (5%) | 0.167 | 72/1629 (4%) | 0.785 | 111/1443 (8%) | 0.005 |
| <80% | 62/951 (7%) | 10/331 (3%) | 12/309 (4%) | 40/311 (13%) | ||||
| FEV1/FVC ≥70% | 260/5095 (5%) | <0.001 | 92/2008 (5%) | 0.769 | 64/1695 (4%) | 0.003 | 104/1392 (7%) | 0.001 |
| <70% | 77/792 (10%) | 10/187 (5%) | 20/243 (8%) | 47/362 (13%) | ||||
FEV1 % = forced expiratory volume-one second percentage; FVC % = forced vital capacity percentage; ABI PTA = ankle–brachial index posterior tibial artery.
Table 3.
Adjusted logistic regression model of pulmonary function and the presence of carotid and femoral atheromatous plaques.
Table 3.
Adjusted logistic regression model of pulmonary function and the presence of carotid and femoral atheromatous plaques.
| Variables | Presence of Carotid Plaques | ||
| OR | 95% CI | p Value | |
| FEV1 % (5-unit % change) | 0.974 | 0.959–0.989 | 0.001 |
| FEV1 %, quartiles | |||
| (108,157) | 1 | ||
| (96,108) | 1.073 | 0.917–1.256 | 0.377 |
| (84,96) | 1.174 | 1.002–1.375 | 0.048 |
| (22,84) | 1.27 | 1.079–1.494 | 0.004 |
| FVC % (5-unit % change) | 0.984 | 0.968–1 | 0.055 |
| FVC %: | |||
| ≥80% | 1 | ||
| <80% | 1.097 | 0.941–1.279 | 0.236 |
| FEV1/FVC: | |||
| ≥70% | 1 | ||
| <70% | 1.231 | 1.041–1.457 | 0.015 |
| Variables | Presence of Femoral Plaques | ||
| OR | 95% CI | p Value | |
| FEV1 % (5-unit % change) | 0.995 | 0.979–1.012 | 0.561 |
| FEV1 %, quartiles | |||
| (108,157) | 1 | ||
| (96,108) | 1.018 | 0.865–1.199 | 0.828 |
| (84,96) | 1.097 | 0.93–1.294 | 0.271 |
| (22,84) | 1.009 | 0.85–1.197 | 0.922 |
| FVC % (5-unit % change) | 1.008 | 0.991–1.025 | 0.367 |
| FVC %: | |||
| ≥80% | 1 | ||
| <80% | 0.908 | 0.772–1.069 | 0.248 |
| FEV1/FVC: | |||
| ≥70% | 1 | ||
| <70% | 1.172 | 0.978–1.405 | 0.086 |
| Variables | Pathologic ABI | ||
| OR | 95% CI | p Value | |
| FEV1 % (5-unit % change) | 0.97 | 0.94–1.001 | 0.057 |
| FEV1 %, quartiles | |||
| (108,157) | 1 | ||
| (96,108) | 1.194 | 0.828–1.721 | 0.343 |
| (84,96) | 1.315 | 0.92–1.879 | 0.133 |
| (22,84) | 1.435 | 1.007–2.045 | 0.046 |
| FVC % (5-unit % change) | 0.998 | 0.965–1.032 | 0.920 |
| FVC %: | |||
| ≥80% | 1 | ||
| <80% | 0.902 | 0.661–1.23 | 0.514 |
| FEV1/FVC: | |||
| ≥70% | 1 | ||
| <70% | 1.54 | 1.153–2.057 | 0.004 |
Adjusted by sex, age, blood pressure, cholesterol, BMI, waist circumference, smoking habit, pack-years, prediabetes and hypertension and hypolipidemic treatment. FEV1 % = forced expiratory volume-one second percentage; FVC % = forced vital capacity percentage.
Table 4.
Adjusted logistic regression model of pulmonary function and the presence of carotid/femoral atheromatous plaques stratified by smoking status.
Table 4.
Adjusted logistic regression model of pulmonary function and the presence of carotid/femoral atheromatous plaques stratified by smoking status.
| Variables | Presence of Carotid Plaques | |||||
| Never Smokers | p Value | Former Smokers | p Value | Current Smokers | p Value | |
| FEV1 % (5-unit % change) | 0.978 (0.955–1.002) | 0.073 | 0.986 (0.958–1.015) | 0.332 | 0.953 (0.925–0.982) | 0.002 |
| FEV1 %, quartiles | ||||||
| (108,157) | 1 | 1 | 1 | |||
| (96,108) | 1.186 (0.943–1.492) | 0.145 | 0.884 (0.667–1.172) | 0.391 | 1.191 (0.845–1.681) | 0.318 |
| (84,96) | 1.246 (0.977–1.588) | 0.076 | 0.942 (0.711–1.246) | 0.674 | 1.429 (1.026–1.991) | 0.035 |
| (22,84) | 1.211 (0.935–1.567) | 0.146 | 1.095 (0.818–1.465) | 0.543 | 1.599 (1.151–2.22) | 0.005 |
| FVC % (5-unit % change) | 0.983 (0.959–1.008) | 0.171 | 1.003 (0.972–1.034) | 0.861 | 0.967 (0.937–0.999) | 0.041 |
| FVC %: | ||||||
| 80% | 1 | 1 | 1 | |||
| <80% | 1.042 (0.815–1.331) | 0.743 | 1.146 (0.868–1.514) | 0.336 | 1.11 (0.835–1.476) | 0.472 |
| FEV1/FVC: | ||||||
| ≥70% | 1 | 1 | 1 | |||
| <70% | 1.218 (0.887–1.671) | 0.223 | 1.39 (1.025–1.886) | 0.034 | 1.143 (0.873–1.495) | 0.331 |
| Variables | Presence of Femoral Plaques | |||||
| Never Smokers | p Value | Former Smokers | p Value | Current Smokers | p Value | |
| FEV1 % (5-unit % change) | 1.008 (0.983–1.033) | 0.538 | 1.01 (0.981–1.041) | 0.492 | 0.95 (0.918–0.984) | 0.004 |
| FEV1 %, quartiles | ||||||
| (108,157) | 1 | 1 | 1 | |||
| (96,108) | 0.925 (0.73–1.172) | 0.519 | 1.039 (0.778–1.388) | 0.796 | 1.269 (0.879–1.833) | 0.203 |
| (84,96) | 0.985 (0.769–1.261) | 0.903 | 0.991 (0.742–1.323) | 0.951 | 1.64 (1.146–2.345) | 0.007 |
| (22,84) | 0.899 (0.69–1.171) | 0.428 | 0.829 (0.614–1.12) | 0.222 | 1.654 (1.158–2.362) | 0.006 |
| FVC % (5-unit % change) | 1.016 (0.99–1.042) | 0.233 | 1.029 (0.997–1.062) | 0.077 | 0.969 (0.935–1.004) | 0.079 |
| FVC %: | ||||||
| ≥80% | 1 | 1 | 1 | |||
| <80% | 0.85 (0.66–1.093) | 0.206 | 0.857 (0.643–1.142) | 0.292 | 1.15 (0.819–1.614) | 0.420 |
| FEV1/FVC: | ||||||
| ≥70% | 1 | 1 | 1 | |||
| <70% | 0.96 (0.699–1.318) | 0.801 | 1.218 (0.886–1.674) | 0.225 | 1.355 (0.985–1.864) | 0.062 |
| Variables | Pathologic ABI | |||||
| Never Smokers | p Value | Former Smokers | p Value | Current Smokers | p Value | |
| FEV1 % (5-unit % change) | 1.02 (0.965–1.077) | 0.485 | 0.98 (0.919–1.045) | 0.534 | 0.928 (0.882–0.975) | 0.003 |
| FEV1 %, quartiles | ||||||
| (108,157) | 1 | 1 | 1 | |||
| (96,108) | 1.087 (0.643–1.841) | 0.755 | 1.63 (0.785–3.385) | 0.190 | 1.081 (0.52–2.247) | 0.836 |
| (84,96) | 0.969 (0.543–1.727) | 0.915 | 1.542 (0.746–3.189) | 0.243 | 1.718 (0.891–3.312) | 0.106 |
| (22,84) | 1.006 (0.554–1.827) | 0.983 | 1.44 (0.685–3.028) | 0.337 | 1.971 (1.039–3.741) | 0.038 |
| FVC % (5-unit % change) | 1.028 (0.972–1.088) | 0.333 | 1.039 (0.969–1.114) | 0.282 | 0.951 (0.9–1.004) | 0.068 |
| FVC %: | ||||||
| ≥80% | 1 | 1 | 1 | |||
| <80% | 0.552 (0.281–1.085) | 0.085 | 0.545 (0.264–1.123) | 0.100 | 1.4 (0.913–2.145) | 0.123 |
| FEV1/FVC: | ||||||
| ≥70% | 1 | 1 | 1 | |||
| <70% | 1.124 (0.566–2.231) | 0.738 | 1.59 (0.896–2.821) | 0.113 | 1.648 (1.102–2.464) | 0.015 |
Adjusted by sex, age, blood pressure, cholesterol, BMI, waist circumference, prediabetes and hypertension and hypolipidemic treatment. Former and current smokers also adjusted by pack-years. FEV1 % = forced expiratory volume-one second percentage; FVC % = forced vital capacity percentage.
Table 5.
Linear regression model exploring the differences between former and current smoking in relation to lung function (FEV1 and FVC), adjusted by age, sex, BMI and waist circumference.
Table 5.
Linear regression model exploring the differences between former and current smoking in relation to lung function (FEV1 and FVC), adjusted by age, sex, BMI and waist circumference.
| Variables | FEV1 % | FEV1/FVC | ||||
|---|---|---|---|---|---|---|
| Linear Regression Coefficient (β) | 95% CI | p Value | Linear Regression Coefficient (β) | 95% CI | p Value | |
| Former smoker | Ref | Ref | ||||
| Current smoker | −5.34 | −6.54 to −4.14 | <0.001 | −2.13 | −2.64 to −1.62 | <0.001 |
| Age | −0.42 | −0.52 to −0.31 | <0.001 | −0.27 | −0.31 to −0.22 | <0.001 |
| Sex, female | 7.07 | 5.71 to 8.43 | <0.001 | 0.41 | −0.16 to 0.99 | 0.160 |
| BMI | −0.12 | −0.27 to 0.02 | 0.096 | 0.14 | 0.08 to 0.21 | <0.001 |
| High waist circumference (Male ≥102 cm Female ≥88 cm) | −3.19 | −4.77 to −1.61 | <0.001 | 0.33 | −0.34 to 1.00 | 0.332 |
FEV1 % = forced expiratory volume-one second percentage; FEV1/FVC = forced expiratory volume-one second to forced vital capacity ratio; BMI = body mass index.
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González, J.; Gracia-Lavedan, E.; Gómez, S.; Barril, S.; Godoy, P.; Bermúdez-López, M.; Betriu, A.; Fernández, E.; Lecube, A.; Pamplona, R.; et al. Lung Function Impairment Is Related to Subclinical Atherosclerosis Only in Active Smokers. J. Vasc. Dis. 2022, 1, 24-35. https://doi.org/10.3390/jvd1010004
AMA Style
González J, Gracia-Lavedan E, Gómez S, Barril S, Godoy P, Bermúdez-López M, Betriu A, Fernández E, Lecube A, Pamplona R, et al. Lung Function Impairment Is Related to Subclinical Atherosclerosis Only in Active Smokers. Journal of Vascular Diseases. 2022; 1(1):24-35. https://doi.org/10.3390/jvd1010004
Chicago/Turabian StyleGonzález, Jessica, Esther Gracia-Lavedan, Silvia Gómez, Silvia Barril, Pere Godoy, Marcelino Bermúdez-López, Angels Betriu, Elvira Fernández, Albert Lecube, Reinald Pamplona, and et al. 2022. "Lung Function Impairment Is Related to Subclinical Atherosclerosis Only in Active Smokers" Journal of Vascular Diseases 1, no. 1: 24-35. https://doi.org/10.3390/jvd1010004
APA StyleGonzález, J., Gracia-Lavedan, E., Gómez, S., Barril, S., Godoy, P., Bermúdez-López, M., Betriu, A., Fernández, E., Lecube, A., Pamplona, R., Purroy, F., Farràs, C., Barbé, F., Torres, G., de Batlle, J., & on behalf of the ILERVAS Project Collaborators. (2022). Lung Function Impairment Is Related to Subclinical Atherosclerosis Only in Active Smokers. Journal of Vascular Diseases, 1(1), 24-35. https://doi.org/10.3390/jvd1010004
