|Year : 2019 | Volume
| Issue : 3 | Page : 117-120
Ultrasonographic assessment of subclinical atherosclerosis in smokers aged <40 years
Taruna Singh MD (Radiotherapy) 1, Ritu Karoli MD (General Medicine) 2, Sachin Khanduri MD (Radiodiagnosis) 1, Nikhil Gupta MD (General Medicine) 2, Prem Shanker Singh MD (General Medicine) 2
1 Department of Radiodiagnosis, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
2 Department of Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Web Publication||31-Jul-2019|
Dr. Ritu Karoli
Department of Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow - 226 010, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Cigarette smoking is a well-known risk factor for developing coronary artery disease. Ultrasonography is an excellent tool which is noninvasive and cheap, might be utilized as a cost effective method to screen the high risk population. There are many surrogate markers of atherosclerosis which can be assessed with the help of ultrasonography such as carotid intima media thickness (CIMT), Flow mediated vasodilatation (FMD) and Ankle brachial index (ABI). Aim of our study was to assess atherosclerotic risk markers non invasively using ultrasonography as a tool in smokers less than forty years. Materials and Methods: All subjects amongst patient's attendants or hospital staff aged more than 18 years and less than 40 years with history of smoking were enrolled as cases and age, gender and BMI matched non smokers were defined as controls. Anthropometric and biochemical parameters were recorded and CIMT, FMD and ABI were assessed. Results: Amongst smokers, average duration of smoking was 8.5±2.5 years. They had higher systolic and diastolic blood pressures than controls. The smokers had higher total cholesterol, triglycerides and LDL. Smokers presented with higher values of CIMT and lower values of FMD and ABI than non-smoker controls. Conclusion: Subclinical markers are present even in young smokers who are less than forty years. Ultrasonography is a good modality to assess the surrogate markers of subclinical atherosclerosis.
Keywords: Atherosclerosis, risk markers, smoking, ultrasonography
|How to cite this article:|
Singh T, Karoli R, Khanduri S, Gupta N, Singh PS. Ultrasonographic assessment of subclinical atherosclerosis in smokers aged <40 years. J Clin Prev Cardiol 2019;8:117-20
|How to cite this URL:|
Singh T, Karoli R, Khanduri S, Gupta N, Singh PS. Ultrasonographic assessment of subclinical atherosclerosis in smokers aged <40 years. J Clin Prev Cardiol [serial online] 2019 [cited 2020 Mar 28];8:117-20. Available from: http://www.jcpconline.org/text.asp?2019/8/3/117/263833
| Introduction|| |
Cigarette smoking is an important preventable risk factor for atherosclerosis that leads to cardiovascular (CV) morbidity and mortality., Previous studies based on coronary angiography have demonstrated that cigarette smoking was associated with progression of atherosclerosis, and increased occurrence of CV events.
Several pathophysiologic effects of cigarette smoke exposure on CV function have been elucidated in experimental and clinical studies. Active as well as passive cigarette smoke exposure increases endothelial dysfunction. Smoking initiates and aggravates inflammatory cascade at the vessel wall and enhances vascular prothrombotic effects., There is no concrete evidence available, demonstrating that smoking has not only direct but also many direct effects that escalate process of atherosclerosis.
Ultrasonography (USG) is an excellent tool which is easily available, noninvasive, and cheap and might be used as a cost-effective method to screen the high-risk individuals for the purpose of diagnosis and prognosis of the disease process. There are many surrogate markers of subclinical atherosclerosis which can be assessed with the help of USG such as carotid intima-media thickness (CIMT), flow-mediated vasodilatation (FMD), and ankle–brachial index (ABI) and have been studied and well correlated with coronary atherosclerosis in our population.
Few researchers have attempted to assess different parameters of subclinical atherosclerosis for the risk stratification in smokers in the past., This work intends to better define the vascular damage of smoking in young healthy people, in order to substantiate evidence of the impact of smoking on the vascular tree which can emphasize the importance of preventive strategies in this productive age group. The aim of our study was to assess surrogate noninvasive atherosclerotic risk markers using USG as a tool in smokers <40 years.
| Materials and Methods|| |
This was a hospital-based, cross-sectional, and observational study conducted from January 2016 to June 2016. It included all participants aged >18 years and <40 years with a history of smoking among patients' attendants or hospital staff from the Medical Outpatient Departments of Era's Lucknow Medical College, Lucknow, as cases and age-, gender-, and body mass index (BMI)-matched nonsmoker participants as controls. A nonsmoker was defined as a person who had never smoked.
All participants who presented with a known history of diabetes mellitus or hypertension, coronary artery disease, peripheral artery disease (PAD), cerebrovascular disease, congestive cardiac failure, valvular heart disease, chronic kidney or liver disease, and autoimmune or chronic inflammatory diseases were excluded from the study.
In all study participants, demographic and anthropometric characteristics (age, sex, height, weight, BMI, and waist circumference) and blood pressure (BP) and laboratory parameters including fasting plasma glucose, hemoglobin A1c, low-density lipoprotein (LDL), high-density lipoprotein, and triglycerides (TGs) and renal and liver profile were assessed. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all the study participants.
Assessment of atherosclerosis markers
It was determined from BP measurement in both upper limbs and ankles, with the participants in supine position. Systolic BP (SBP) from the brachial artery in the antecubital fossa was measured using a BP cuff and high-resolution B-mode ultrasound equipped with continuous-wave Doppler 7-MHz probe. In the lower limbs, SBP from the posterior tibial or dorsalis pedis arteries was measured with Doppler detection by placing a BP cuff at the ankle. ABI was calculated as the ratio of the highest SBP measured at the ankle to the highest SBP measured at the brachial artery, and ABI of <0.90 was taken cutoff to define PAD.
Flow-mediated dilatation (FMD) measurement
Endothelial function was measured by USG assessment of right brachial artery dimensions. The diameter of the right brachial was measured twice, first at rest then after inducing reactive hyperemia with the help of pneumatic cuff. It was carried out after an overnight fast in a cool and quiet room with B-mode ultrasound scanner (Siemens, Germany) using 10-MHz linear transducer. The diameter of the right brachial artery was measured 2–8 cm above the antecubital space in the end-diastolic phase from one media–adventitia interface to the other at the clearest part three times, and an average was taken. After the detection of the right transducer position, skin was marked and arm was kept in the same position. The BP cuff was tied on the upper arm and inflated to suprasystolic levels kept inflated for 4 min. Sixty seconds after the cuff was released, brachial artery dimensions were again measured. The maximum diameter measurement was defined as the average of three consecutive diameter measurements.
Carotid intima-media thickness
It was measured by B-mode ultrasound using linear probe at frequency of 10 MHz. The common carotid arteries were scanned at the level of bifurcation on both sides, and mean value was used for analysis. The intima-media thickness was measured in the far wall of the arteries at sites identified as diffuse and continuous projections with the greatest distance between the luminal–intimal interface and media–adventitial interface but without atherosclerotic plaques. Localized lesions >2-mm thickness was considered to be atherosclerotic plaques.
Data analyses were performed using SPSS for Windows, version 11.5 (SPSS, Chicago, USA). Data were expressed as mean ± standard deviation or number and percentage. The normal data distribution was analyzed with the Kolmogorov–Smirnov test. Baseline clinical parameters were compared between the subgroups by Chi-square or Student's test. Pearson's correlation test was utilized to study the correlation between atherosclerotic markers and other variables. P < 0.05 was considered significant.
| Results|| |
The present study included 50 smokers aged <40 years and compared with another group of nonsmokers who were age gender and also BMI matched who had never smoked and they served as controls. [Table 1] shows the baseline characteristics of study participants, and no statistically significant difference was observed in anthropometric parameters between the two groups.
Among smokers, average duration of smoking was 8.5 ± 2.5 years. They had higher SBP and diastolic BP than controls. The smokers had higher total cholesterol, TG, and LDL.
As depicted in [Table 2], smokers presented higher values of CIMT and lower values of FMD and ABI. Mean CIMT was significantly higher (0.76 ± 0.12 vs. 0.54 ± 0.18 mm) in smokers than in controls. The mean increase in brachial artery diameter was 0.26 ± 0.13 mm in patients and 0.48 ± 0.09 mm in controls. This difference was statistically significant (P = 0.001), indicating an increase in diameter with ischemia. Mean brachial artery diameter at baseline was 3.8 ± 1.9 mm in smokers and 3.67 ± 2.3 mm in controls. The difference was not statistically significant (P = 0.5). Mean FMD was 8.12% ±2.56% and 13.26% ±2.8% in smokers and in controls, respectively [Table 2]. The difference was statistically significant (P = 0.01).
The study participants who had ABI <0.9 and were 13/50 (26%) in smoker group and 1/50 (2%) in nonsmokers. Mean ABI was lower in smokers than nonsmokers (0.96 ± 0.4 vs. 1.0 ± 0.02, P = 0.03), and the difference was statistically significant. All the three atherosclerotic markers such as ABI, CIMT, and FMD had a correlation with duration of smoking. CIMT had a positive correlation (r = 0.42, P = 0.01) while ABI and FMD had a negative correlation (r = −0.32, P = 0.03 and r = −0.37, P = 0.001) with duration of smoking.
| Discussion|| |
The present study included a group of apparently young and healthy men with a history of smoking as cases and age- and BMI-matched controls who were subjected for USG assessment of markers of subclinical atherosclerosis. We found that atherosclerosis, which was evaluated by endothelial dysfunction, CIMT, and ABI, was significantly higher in smokers than in their nonsmoker counterparts.
It has been well documented in the literature that smoking is a major proponent of atherosclerosis and it is responsible for accelerated atherosclerosis. The studies have shown confirm benefits of smoking cessation in the form of CV risk reduction., Smoking causes endothelial injury of the vessel wall and enhances atherosclerotic plaque formation. Endothelial dysfunction is an early event in pathogenesis of atherosclerotic process. It is characterized by an imbalance between vasodilation and vasoconstriction, a pro-inflammatory phenotype of the endothelial cells, increased adhesion of monocytes, and reduced bioavailability of nitric oxide.,,
Endothelial function assessed by arterial FMD is a validated measure of subclinical atherosclerosis and is defined as the percent by which the arteries dilate in response to an increase in blood flow. FMD is a clinical prognostic indicator of endothelial function and future CV events. Tandon et al. demonstrated the association of FMD with coronary atherosclerosis in Indian patients. The results of our study have shown a significantly lower mean baseline FMD values in smokers compared with nonsmokers, which is in concordance to previous studies.,,
ABI, the ratio of ankle to brachial SBP, is a simple, objective, and noninvasive method to diagnose and to observe PAD. Many studies have proven it to be a good surrogate marker of generalized and coronary atherosclerosis in Indian patients., We demonstrated that smokers had a lower mean ABI showing the significant effect of smoking in the PAD development similar to other workers.
CIMT is another noninvasive technique to detect subclinical atherosclerosis and is associated with multiple CV risk factors and future CV mortality. The correlation of CIMT with coronary atherosclerosis has been shown by various other workers in our population., The demonstration of higher CIMT values in apparently healthy smokers than in age-, sex-, and BMI-matched nonsmokers in our study was similar to study performed on younger healthy university students. It was also in accordance with other previous studies.,
The purpose of our study was to perform atherosclerotic imaging in young individuals who are more at risk of future CV events. This type of screening strategies can emphasize cigarette smoking and improve long-term health outcomes. Imaging-based biomarkers for CV disease (CVD) provide important prognostic information, to complement traditional clinical risk stratification methods and diagnose subclinical CVD in asymptomatic patients with risk factors.
Given that age, gender, and BMI can influence the pathogenesis of atherosclerosis and its major determinants, i.e., FMD and CIMT, we matched cases and controls to eliminate as far as possible these effects on FMD and CIMT. This study was based on single observer-based onetime measurements, so validity and reproducibility of different parameters could not be tested.
There are not much-published data regarding the association between smoking and subclinical atherosclerotic risk markers in our population which is the novelty of our study which has got several limitations. First, this study was done on healthy and young individuals enrolled from hospital premises, so it is not directly comparable either to the community at large or to the clinical setting. Extrapolating these results to participants with comorbidities must be taken with caution. The study had a very small sample size, and being of cross-sectional in design, the causative nature of the associations could not be established. Further research including large number of patients is needed to provide robust evidence in this regard.
| Conclusion|| |
Smoking is one of the most important risk factors of atherosclerosis which is preventable. Endothelial dysfunction is an early event in atherosclerosis. Subclinical atherosclerotic markers are present even in young smokers who are <40 years. USG is a good modality to assess the surrogate markers of subclinical atherosclerosis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Escobedo LG, Zack MM. Comparison of sudden and nonsudden coronary deaths in the United States. Circulation 1996;93:2033-6.
Lakier JB. Smoking and cardiovascular disease. Am J Med 1992;93:8S-12S.
Kim JA, Chun EJ, Lee MS, Kim KJ, Choi SI. Relationship between amount of cigarette smoking and coronary atherosclerosis on coronary CTA in asymptomatic individuals. Int J Cardiovasc Imaging 2013;29 Suppl 1:21-8.
Waters D, Lespérance J, Gladstone P, Boccuzzi SJ, Cook T, Hudgin R, et al.
Effects of cigarette smoking on the angiographic evolution of coronary atherosclerosis. A Canadian coronary atherosclerosis intervention trial (CCAIT) substudy. CCAIT study group. Circulation 1996;94:614-21.
Njølstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark study. Circulation 1996;93:450-6.
Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: An update. J Am Coll Cardiol 2004;43:1731-7.
Benowitz NL. Cigarette smoking and cardiovascular disease: Pathophysiology and implications for treatment. Prog Cardiovasc Dis 2003;46:91-111.
Csordas A, Bernhard D. The biology behind the atherothrombotic effects of cigarette smoke. Nat Rev Cardiol 2013;10:219-30.
Ezhumalai B, Krishnasuri SD, Jayaraman B. Comparison of diagnostic utilities of ankle-brachial index and carotid intima-media thickness as surrogate markers of significant coronary atherosclerosis in Indians. Indian Heart J 2013;65:137-41.
McEvoy JW, Nasir K, DeFilippis AP, Lima JA, Bluemke DA, Hundley WG, et al.
Relationship of cigarette smoking with inflammation and subclinical vascular disease: The multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 2015;35:1002-10.
Koo HS, Gil TY, Lee HW, Lee K, Hong YM. Effects of smoking on the pulse wave velocity and ankle-brachial index in adolescents. Korean Circ J 2007;37:414-8.
Bryant A, Cerfolio RJ. Differences in epidemiology, histology, and survival between cigarette smokers and never-smokers who develop non-small cell lung cancer. Chest 2007;132:185-92.
Aboyans V, Criqui MH, Abraham P, Allison MA, Creager MA, Diehm C, et al.
Measurement and interpretation of the ankle-brachial index: A scientific statement from the American Heart Association. Circulation 2012;126:2890-909.
Erhardt L. Cigarette smoking: An undertreated risk factor for cardiovascular disease. Atherosclerosis 2009;205:23-32.
Pipe AL, Papadakis S, Reid RD. The role of smoking cessation in the prevention of coronary artery disease. Curr Atheroscler Rep 2010;12:145-50.
van den Berkmortel FW, Wollersheim H, van Langen H, Smilde TJ, den Arend J, Thien T, et al.
Two years of smoking cessation does not reduce arterial wall thickness and stiffness. Neth J Med 2004;62:235-41.
Messner B, Bernhard D. Smoking and cardiovascular disease: Mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol 2014;34:509-15.
Li H, Srinivasan SR, Chen W, Xu JH, Li S, Berenson GS, et al.
Vascular abnormalities in asymptomatic, healthy young adult smokers without other major cardiovascular risk factors: The Bogalusa heart study. Am J Hypertens 2005;18:319-24.
Heeschen C, Weis M, Cooke JP. Nicotine promotes arteriogenesis. J Am Coll Cardiol 2003;41:489-96.
Li J, Liu S, Cao G, Sun Y, Chen W, Dong F, et al.
Nicotine induces endothelial dysfunction and promotes atherosclerosis via GTPCH1. J Cell Mol Med 2018;22:5406-17.
Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: Implications for the assessment of endothelial function. J Physiol 2005;568:357-69.
Tandon S, Bhargava K, Gupta H, Bansal M, Kasliwal RR. Non-invasive assessment of endothelial function by brachial artery flow mediated vasodilatation and its association with coronary artery disease: An Indian perspective. J Indian Med Assoc 2004;102:243-6, 251-2.
Heffernan KS, Karas RH, Patvardhan EA, Kuvin JT. Endothelium-dependent vasodilation is associated with exercise capacity in smokers and non-smokers. Vasc Med 2010;15:119-25.
Ozaki K, Hori T, Ishibashi T, Nishio M, Aizawa Y. Effects of chronic cigarette smoking on endothelial function in young men. J Cardiol 2010;56:307-13.
Yufu K, Takahashi N, Hara M, Saikawa T, Yoshimatsu H. Measurement of the brachial-ankle pulse wave velocity and flow-mediated dilatation in young, healthy smokers. Hypertens Res 2007;30:607-12.
Raman PG, Thakur BS, Mathew V. Ankle brachial index as a predictor of generalized atherosclerosis. J Assoc Physicians India 2001;49:1074-7.
Sarangi S, Srikant B, Rao DV, Joshi L, Usha G. Correlation between peripheral arterial disease and coronary artery disease using ankle brachial index-a study in Indian population. Indian Heart J 2012;64:2-6.
Syvänen K, Aarnio P, Jaatinen P, Korhonen P. Effects of age, sex and smoking on ankle-brachial index in a Finnish population at risk for cardiovascular disease. Int J Angiol 2007;16:128-30.
Polak JF, Pencina MJ, Pencina KM, O'Donnell CJ, Wolf PA, D'Agostino RB Sr., et al.
Carotid-wall intima-media thickness and cardiovascular events. N
Engl J Med 2011;365:213-21.
Hansa G, Bhargava K, Bansal M, Tandon S, Kasliwal RR. Carotid intima-media thickness and coronary artery disease: An Indian perspective. Asian Cardiovasc Thorac Ann 2003;11:217-21.
Kasliwal RR, Bansal M, Desai N, Kotak B, Raza A, Vasnawala H, et al.
Astudy to derive distribution of carotid intima media thickness and to determine its COrrelation with cardiovascular risk factors in asymptomatic NationwidE Indian population (SCORE-india). Indian Heart J 2016;68:821-7.
Lerant B, Straesser C, Kovacs RK, Olah L, Kardos L, Sciba L. Morphological, hemodynamic and stiffness changes in arteries of young smokers. Perspect Med 2012;1:152-5.
Howard G, Wagenknecht LE, Burke GL, Diez-Roux A, Evans GW, McGovern P, et al.
Cigarette smoking and progression of atherosclerosis: The atherosclerosis risk in communities (ARIC) study. JAMA 1998;279:119-24.
Johnson HM, Piper ME, Jorenby DE, Fiore MC, Baker TB, Stein JH, et al.
Risk factors for subclinical carotid atherosclerosis among current smokers. Prev Cardiol 2010;13:166-71.
[Table 1], [Table 2]