Pulse wave velocity, augmentation index and arterial age in students

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1 Pulse wave velocity, augmentation index and arterial age in students IOANA MOZOS 1, SERBAN GLIGOR 2 1 Department of Functional Sciences Victor Babes University of Medicine and Pharmacy Timisoara ROMANIA ioana_mozos@yahoo.com 2 Department of Physical Therapy and Special Motion West University Timisoara ROMANIA Abstract: - Atherosclerosis is initiated in young years, and arterial stiffness and endothelial dysfunction are markers of subclinical atherosclerosis and predictors of cardiovascular risk. The aim of the present study was to investigate the arterial function in young people and to identify factors associated with early vascular aging. A total of 35 students underwent arteriography and data about family history of cardiovascular disease, smoking, coffee consumption, physical activity, healthy diet containing fruit and vegetables were collected. A positive family history, smoking and early vascular aging were very prevalent in the investigated population (74%, 23% and 57%, respectively). Data about physical activity, healthy food choices, endothelial function and pulse wave velocity were satisfactory. Daily coffee consumption, smoking and a positive family history for cardiovascular diseases are predictors of early arterial aging. The present study is both educative and a screening tool. Key-Words: - Arteriography, pulse wave velocity, augmentation index, arterial age, early arterial aging, lifestyle. 1 Introduction Cardiovascular diseases and atherosclerosis are leading mortality causes in Western countries. Atherosclerosis begins at youth, causing cholesterol deposits in the arteries and vascular remodeling, with clinical signs only in adults [1]. Arterial stiffness and endothelial dysfunction are noninvasive markers of subclinical atherosclerosis and predictors of cardiovascular risk. Arterial stiffness, an expression of reduced elastic properties of the arteries, and endothelial dysfunction, can be assessed using arteriography (pulse wave velocity and augmentation index, respectively). Arterial age is a useful clinical tool for investigation and guidance of individuals at increased cardiovascular risk [2]. Vascular aging is the effect of oxidative stress, endothelial dysfunction, formation of advanced glycation endproducts, telomere damage, depletion of vascular progenitor cells, accumulation of senescent endothelial and vascular smooth muscle cells, vascular inflammation, microvascular rarefaction, increased arterial stiffness, and is accentuated in the presence of classical cardiovascular risk factors [2, 3]. Arterial stiffness is an ongoing process, due to the rupture of the elastin fibers, accumulation of collagen, fibrosis and necrosis of muscle fibers, inflammation and calcium deposits in the vascular wall [4]. It starts in the early years of life and advances with age [5]. Prophylactic measures should be given special attention, because persons at high risk for developing cardiovascular diseases are unaware of their status, atherosclerosis has a long latency time, and the first disease symptom may be the last one. Without effective prevention programs, the prevalence of fatal cardiovascular complications will continue to increase. It is extremely important, to identify, as early as possible, factors, which are able to influence the atherogenic process. Cardiovascular risk factors have their limitations because they consider only coronary complications as endpoint. Arterial stiffness and endothelial dysfunction are better markers of vascular damage. Pulse wave velocity has a better predictive value than classical cardiovascular risk factors, possibly because it cummulates the effect of both known and nonidentified cardiovascular risk factors on the large arteries [2,6]. ISBN:

2 2 Problem Formulation The aim of the present study was to analyze arterial function in young people (students) and to identify factors associated with early elevation of arterial stiffness and early vascular aging. 2.1 Materials and methods A total of 35 students underwent arteriography, and data about family history, personal disease history, smoking habits, physical activity, coffee consumption, use of contraceptives, diet containing fruits and vegetables, were collected Study population A total 21 Medical students from the Victor Babes University of Medicine and Pharmacy, and 14 students from the Physical Education and Sports Faculty, from the West University, were enrolled in the study. The investigations conformed to the Declaration of Helsinki [7]. A written informed consent was obtained from each participant. Participants in which pulse wave velocity, augmentation indices and arterial age could not be determined, were excluded from the study. The main reason was very low blood pressure (Systolic blood pressure < 100 mmhg). Family history was considered positive if cardiovascular diseases or diabetes mellitus were mentioned. Smoking habits were also self-reported, and data about number of cigarettes and smoking period were collected, as well. Physical activity was considered if the participants reported at least 30 minutes every day, including normal daily activity. Daily coffee consumption, use of contraceptives, daily diet containing fruits and vegetables were, also, self-reported Arteriography Arteriography was performed using a Medexpert device (TensioMed Ltd, Budapest, Hungary). Systolic and diastolic blood pressure, mean arterial pressure, brachial and aortic augmentation index, pulse wave velocity (PWV), the diastolic reflection area (DRA), diastolic and systolic area index (DAI and SAI), and arterial age were assessed, after 10 minutes rest, in supine position, in a quiet room, with normal temperature (22±1 C). The students were previously asked not to eat, smoke or drink caffeinated beverages or alcohol 4 hours before the investigation. The participants were not allowed to speak or move during the recordings. PWV was measured based on an oscillometric method, using an upper arm cuff, according to the criteria of the Expert consensus document on arterial stiffness [6], and was considered optimal if < 7m/s, and arterial age increased (early vascular aging) if higher than the biological age. Blood pressure values were classified according to the criteria of the European Society of Hypertension and European Society of Cardiology [8] Statistics Categorical data are given as numbers and percentages, continuous data are given as means ± standard deviation. Linear and multiple regression analysis, and odds ratio were used as statistical methods. 3 Results The characteristics of the study population are included in Table 1. Table 1. Characteristics of the study population Parameter Age (mean±sd) (years) 21±3.81 Gender (male) (%) 11 (31%) Body mass index (kg/m 2 ) 23±4.6 Overweight and obese (%) 10 (29%) Positive family history for 26 (74%) cardiovascular diseases and diabetes mellitus (%) Smokers (%) 8 (23%) Daily physical activity (%) 28 (80%) Use of contraceptives (%) 3 (9%) Daily coffee consumption (%) 6 (17%) Daily diet containing fruits and 18 (51%) vegetables (%) Systolic blood pressure (mmhg) 119±13 Diastolic blood pressure (mmhg) 68±9 Pulse pressure (mmhg) 51±10 Grade 1 hypertension (%) 3 (9%) High normal blood pressure (%) 6 (17%) Mean arterial pressure (mmhg) 85±9 Heart rate (beats/minute) 80±13 Aix brach (Brachial augmentation -59±14 index) (%) Aix Ao (Aortic augmentation 6.94±1.15 index) (%) DRA (diastolic reflection area) 61±3.42 SAI (systolic area index) (%) 47±4.79 ISBN:

3 DAI (diastolic area index) (%) 53±4.7 PWV (Pulse wave velocity) (m/s) 7.25±1.6 AA (Arterial age) (years) 28±13 Increased AA (%) 20 (57%) 3.1. Linear and multiple regression analysis Multiple regression analysis revealed significant associations between family history of cardiovascular diseases, physical activity and brachial and aortic augmentation index, respectively (Table 2). Linear regression analysis revealed significant associations between physical activity and pulse wave velocity and diastolic reflection area, respectively. Daily coffee consumption was significantly associated with the brachial augmentation index and arterial age. Significant associations were found between smoking and aortic augmentation index, pulse wave velocity and arterial age, respectively. Daily diet including fruits and vegetables was significantly associated with brachial augmentation index, pulse wave velocity and arterial age (Table 3). Table 2. Factors significantly associated with positive family history of cardiovascular diseases and daily physical activity. Multiple regression analysis. Significance F<0.01 Parameter Associated with Family Aix brach history p < 0.05 Aix Ao Physical activity p = Aix brach p < 0.01 Aix Ao p = MR R 2 Adj. R MR = multiple R (multiple correlation coefficient) R 2 = R square = coefficient of determination Adj. R = adjusted R = the coefficient of determination adjusted for the number of independent variables in the regression model Aix brach = brachial augmentation index Aix Ao = aortic augmentation index Family history = positive family history for cardiovascular disease and diabetes mellitus Physical activity = at least 30 minutes of physical activity, including normal daily activity. Table 3. Linear regression analysis Associated MR R Adj. F parameters square R Family history < Aix brach Family history <0.01 Aix Ao Physical <0.01 activity - PWV Physical <0.01 activity - DRA Coffee consumption Aix brach Daily coffee consumption - AA Smoking Aix Ao Smoking PWV Smoking - AA F-V diet Aix brach <0.01 F-V diet <0.01 PWV F-V diet - AA <0.01 MR = multiple R (multiple correlation coefficient) R square = coefficient of determination Adj. R = adjusted R = the coefficient of determination adjusted for the number of independent variables in the regression model Aix brach = brachial augmentation index Aix Ao = aortic augmentation index PWV = pulse wave velocity DRA = diastolic reflection area AA = arterial age F-V diet = daily diet containing fruits and vegetables Family history = positive family history for cardiovascular disease and diabetes mellitus Physical activity = at least 30 minutes of physical activity, including normal daily activity 3.2. Odds ratio An increased arterial age was more likely in participants with a positive family history, smokers and daily coffee drinkers (Table 4). ISBN:

4 Table 4. Increased arterial age Predictors of Odds ratio 95%CI increased arterial age Positive family history for cardiovascular diseases and diabetes mellitus Smoking Daily coffee drinkers Pulse wave velocity was, also, more likely to be >7m/s in students with positive family history, smokers and daily coffee drinkers (Table 5). Table 5. Predictors of pulse wave velocity >7m/s Predictors of Odds ratio 95% CI PWV > 7m/s Positive family history for cardiovascular diseases and diabetes mellitus Smoking Daily coffee drinkers 4 Discussions. Conclusions The present study identifies lifestyle factors and positive family history of cardiovascular diseases as early predictors of early vascular aging. Family history of cardiovascular disease and diabetes mellitus was reported by most of the participants (74%). Grade 1 hypertension was detected in 3 participants (9%) and high normal blood pressure values in 6 (17%) students. The white coat effect on blood pressure will be determined by subsequent follow-up and monitoring of blood pressure. There is evidence that in patients with borderline hypertension, arterial stiffening may precede the development of hypertension, and distensibility and compliance are significantly reduced [9, 10]. One of the medical students, previously diagnosed with type 1 diabetes mellitus had an arterial age of more than 60 years. DRA and DAI are diastolic coronary filling parameters, and if impaired, could be early detectors of myocardial ischemia. According to the results of the present study, they are significantly associated with daily physical activity. Pulse wave velocity is the speed at which the pressure waveforms travel along the aorta and large arteries during each cardiac cycle, a measure of arterial stiffness [2]. A pulse wave velocity up to 7 m/s was considered optimal. Values ranging between 7 and 9.7 m/s were previously considered normal, and between 9.7 and 12 m/s elevated. There were only two participants with a PWV higher than 9.7 m/s, meaning an early deterioration of the arterial wall elasticity. Participants with a positive family history for cardiovascular disease, smokers and daily coffee drinkers were more likely to have normal and not optimal pulse wave velocity and an increased arterial age. Considering brachial augmentation index, most of the participants had optimal values (up to - 30%). Endothelial dysfunction was not detected. Despite normal PWV and normal endothelial function, early vascular aging was very prevalent in the present study. An increased arterial age was associated with positive family history of cardiovascular diseases and diabetes mellitus, smoking and daily coffee consumption. The students were informed about the results and the significance of the measurements. The higher-risk participants received additional information about healthy lifestyle and parameters which should be monitored. The present study was both educative and a screening tool. It increased the awareness of the importance of modifiable cardiovascular risk factors, and identified students requiring diet and lifestyle interventions. A previous study [11] reported a lower daily intake of fruits and vegetables in medical students (32% in male and 40% in female students) and similar results for daily physical activity (80% and 76% in male and female students, respectively). The prevalence of overweight and obesity was lower compared to the present study (17% versus 29%). Sedentary lifestyle, positive family history for cardiovascular disease and diabetes mellitus, elevated blood pressure, smoking, obesity, diabetes mellitus were previously mentioned as clinical situations associated with arterial stiffness. Previous studies mentioned factors with a possibly influence in the early vascular aging process, including cardiovascular risk factors such as age, diabetes mellitus, smoking, obesity, hypertension, and family history of early cardiovascular disease [2]. The association of coffee consumption, one of the most frequently consumed beverages, with ISBN:

5 cardiovascular disease, remains controversial, due to different study designs, study populations, coffee types and cardiovascular endpoints [12]. Siasos et al. found an improved endothelial function, evaluated using flow mediated dilatation, in elderly chronic coffee drinkers, with established cardiovascular risk factors [12]. The mentioned study was performed in the Ikaria island inhabitants, famous for their high longevity, and used a boiled Greek type of coffee, rich in antioxidants and polyphenols, and a moderate amount of caffeine. Other authors mentioned an acute impairment of the endothelial function due to coffee consumption [13]. Coffee is a major source of antioxidants, improves glucose tolerance, inhibits platelet aggregation, stimulates the production of NO, but has adverse effects on blood cholesterol and hypertension [12]. On the other hand, acute and chronic coffee intake was previously associated with increased arterial stiffness in healthy and hypertensive subjects [12, 14]. In the present study, daily coffee consumption was associated with early vascular aging, and normal, but not optimal PWV values in young participants. Several studies have demonstrated the protective effects of fruit and vegetable consumption against cardiovascular risk [15]. Subjects consuming fruits and vegetables had slower PWV than those with low consumption [15]. The present study shows significant associations between daily fruit and vegetable consumption and endothelial function, arterial age and pulse wave velocity, respectively. The most important limitation of the present study is, the fact that, several data were selfreported: physical activity, smoking, diet content of fruit and vegetables, coffee consumption, which could lead to over- or underestimations. Alcohol consumption, other types of unhealthy diets and psychological stress were not considered. Brachial PWV was also used to assess arterial properties, although aortic PWV was superior in predicting cardiovascular mortality [16]. The study was designed as cross-sectional, and the relative small number of participants cannot provide causative associations. Further, larger follow-up studies are needed to confirm the findings on different populations. Detection of subjects with preclinical atherosclerosis and increased arterial age might represent an effective primary prevention method, important in reducing the burden of fatal cardiovascular complications. Arteriography has the advantage of being an objective, noninvasive, portable, operator-independent, reproducible and convenient oscillometric method for early diagnosis and follow-up of atherosclerosis [17, 18]. As a conclusion, a positive family history for cardiovascular diseases and early vascular aging were very prevalent in the investigated population, with a high prevalence of overweight, obese and smokers. Data on physical activity, healthy food choices, endothelial function and pulse wave velocity were satisfactory. Lifestyle factors and positive family history of cardiovascular diseases are early predictors of early vascular aging. Unhealthy behaviors, including smoking, physical inactivity and unhealthy diets, require further interventions. References: [1] X1. Nunez F, et al. Carotid Artery Stiffness as an Early Marker of Vascular Lesions in Children and Adolescents With Cardiovascular Risk factors, Rev Esp Cardiol, 63(11), 2010, pp [2] X2. Kotsis V, et al. Arterial stiffness and 24 h ambulatory blood pressure monitoring in young healthy volunteers: The early vascular ageing Aristotle University Thessaloniki Study (EVA ARIS Study), Atherosclerosis, 219, 2011, pp [3] X3. Ungvari Z, et al. Mechanisms of Vascular Aging: New Perspectives, J Gerontol A Biol Sci Med Sci, 65A(10), 2010, pp [4] X4. Agabiti Rosei E, et al. Arterial stiffness, hypertension, and rational use of nebivolol, Vascular Health and Risk Management, 5, 2009, pp [5] X5. Mitchell GF, et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham heart study, Hypertension, 43, 2004, pp [6] X6. Laurent S, et al. European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications, Eur Heart J, 27, 2006, pp [7] X7. World Medical Association Declaration of Helsinki Recommendations guiding physicians in biomedical research involving human subjects, Cardiovascular Research, 35(1), 1997, pp. 2-3 [8] X8. Mancia G, et al. Guidelines for the management of arterial hypertension, Eur Heart J, 28, 2007, pp ISBN:

6 [9] X9. Hermeling E, et al. Advances in arterial stiffness assessment, Artery Research, 5, 2011, pp [11] X11. Mozos I, Costea C. Type 2 diabetes risk in medical students. In: Candea V et al. Proceedings of the IVth Congress of the Academia of Romanian Scientists Quality of Life, October 15-17, 2009, Timisoara, Romainia, Orizonturi Universitare Publishuing House, 2009 [12] X12. Siasos G, et al. Consumption of a boiled Greek type of coffee is associated with improved endothelial function: The Ikaria Study, Vascular Medicine, doi: / X [13] X13. De Koning Gans JM, et al. Tea and coffee consumption and cardiovascular morbidity and mortality, Arterioscler Thromb Vasc Biol, 30, 2010, pp [14] X14. Vlachopoulos CV, et al. Effect of chronic coffee consumption on aortic stiffness and wave reflections in hypertensive patients, Eur J Clin Nutr, 61, 2007, pp [15] X15. Aatola H, et al. Lifetime Fruit and Vegetable Consumption and Arterial Pulse [10] X10. Reneman RS, et al. Non-invasive ultrasound in arterial wall dynamics in humans: what have we learned and what remains to be solved, Eur Heart J, 26, 2005, pp Wave Velocity in Adulthood. The Cardiovascular Risk in Young Finns Study, Circulation, 122, 2010, pp [16] X16.Franklin SS, et al. Beyond blood pressure: Arterial stiffness as a new biomarker of cardiovascular disease, J Am Soc Hypertens, 2(3), 2008, pp [17] X17. Locsey L et al. Arterial Stiffness in Chronic Renal Failure and After Renal Transplantation, Transplantation Proceedings, 42, 2010, pp [18] X18. Jatoi NA, et al. Assessment of arterial stiffness in hypertension: comparison of oscillometric (Arteriograph), piezoelectronic (Complior) and tonometric (SphygmoCor) techniques, J Hypertens, 27, 2009, pp ISBN:

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