Cardio-Ankle Vascular Index in Subjects with Dyslipidaemia and Other Cardiovascular Risk Factors

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1 Original Article Journal of Atherosclerosis and Thrombosis Vol. 20, No Cardio-Ankle Vascular Index in Subjects with Dyslipidaemia and Other Cardiovascular Risk Factors Vladimir Soska 1, 2, 3, Michaela Frantisova 4, Petr Dobsak 5, Ladislav Dusek 6, Jiri Jarkovsky 6, Marie Novakova 7, Kohji Shirai 8, Lenka Fajkusova 9, 11 10, 11 and Tomas Freiberger 1 2nd Clinic of Internal Medicine, Masaryk University of Brno, Czech Republic 2 International Clinical Research Center, St. Anne s University Hospital Brno, Brno, Czech Republic 3 Department of Laboratory Methods, Masaryk University of Brno, Czech Republic. 4 Department of Preventive Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic 5 Department of Sports Medicine and Rehabilitation, St. Anne s Faculty Hospital and Masaryk University of Brno, Czech Republic 6 Institute of Biostatistics and Analyses, Faculty of Medicine and Faculty of Science, Masaryk University, Brno, Czech Republic 7 Department of Physiology, Faculty of Medicine, Masaryk University of Brno, Czech Republic 8 Internal Medicine, Sakura Hospital, Medical Center, Toho University, Chiba, Japan 9 Center of Molecular Biology and Gene Therapy, University Hospital Brno, Czech Republic 10 Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic 11 Central European Institute of Technology, Masaryk University, Brno, Czech Republic Aim: The cardio-ankle vascular index (CAVI) is a novel non-invasive marker of arterial stiffness and atherosclerosis. The aim of this work was to examine whether the CAVI value in patients with dyslipidaemia (DLP) is increased by the presence of other cardiovascular risk factors: hypertension, diabetes mellitus, and smoking. Methods: A total of 392 subjects with DLP (166 male, 226 female), with a median age of 58.5 and 5-95 percentile range years were examined. CAVI was measured using the VaSera 1500 system. Results: CAVI correlated significantly with age (p<0.001) and both systolic (p<0.001) and diastolic (p=0.002) blood pressure; higher values were found in men (p=0.034) than in women in the age group. There was no significant difference in CAVI between smokers and non-smokers (p = 0.217) and between subjects with and without diabetes mellitus (p=0.424). CAVI was significantly higher in subjects with hypertension than in the normotensive group (p<0.001) and in statin-treated subjects than in those without statins (p<0.001); however, CAVI values adjusted for age and sex did not differ significantly between these groups. Adjusted CAVI values were higher only in smokers than in non-smokers (former smokers) (p<0.001). Conclusion: The study proves conclusively that the CAVI value in DLP patients is not significantly affected by hypertension and diabetes mellitus, but it is increased by smoking. J Atheroscler Thromb, 2013; 20: Key words; Dyslipidaemia, Cardio-ankle vascular index, Hypertension, Diabetes mellitus, Smoking Introduction Cardiovascular diseases represent the major causes Address for correspondence: Vladimir Soska, Department of Clinical Biochemistry St. Anne s Faculty Hospital Pekarska 53, Brno, Czech Republic vladimir.soska@fnusa.cz Received: August 6, 2012 Accepted for publication: November 25, 2012 of death in developed countries. They arise from the progression of atherosclerosis - a chronic artery disease that develops over many years without clinical symptoms, until its severity narrows the artery and causes a sudden obstruction. Progression of atherosclerosis may be decelerated, stopped or even reversed by intensive treatment of the main cardiovascular risk factors, primarily by aggressive cholesterol lowering. For example, aggressive statin treatment may lead to the reduction

2 444 Soska et al. of both atherosclerotic plaques and thus the incidence of coronary artery disease (CAD) and strokes 1, 2). Therefore, early detection of atherosclerotic plaque development by a simple, quantitative and non-invasive assessment is very important for prevention of future clinical cardiovascular events. A widely used method is the measurement of carotid intima-media thickness, a strong predictor of cardiovascular events, assessed by high-resolution B-mode ultrasonography 3, 4). Another non-invasive method for the detection of early stages of atherosclerosis is the measurement of large artery stiffness by brachial-ankle pulse wave velocity (PWV) 5, 6). Brachial-ankle PWV enables the assessment of both central elastic and peripheral muscular arterial stiffness; it has been shown to be a predictor of coronary artery disease and may serve as a prognostic factor of acute coronary syndrome 7, 8). However, there are several limitations of its use in clinical practice: reproducibility of PWV measurement is relatively low, this method is rather technically difficult and the results of PWV are affected by changes in blood pressure (BP) during measurement since brachial-ankle PWV itself essentially depends on BP 9, 10) ; therefore, another simple method for early detection of atherosclerosis has been researched. Recently, a new non-invasive screening tool for atherosclerosis detection, the cardio-ankle vascular index (CAVI), has been introduced 9). CAVI is measured by a VaSera device (Fukuda Denshi Co., Tokyo, Japan) using sophisticated new oscillometric technology 11). CAVI represents the stiffness of the aorta, femoral artery and tibial artery, and is essentially BP independent because of the adjustment of BP based on a stiffness parameter β 9, 12-15). It is a marker suitable for atherosclerosis assessment in various arteries, primarily the femoral artery, aorta and tibial artery 13). Several studies have shown the usefulness of CAVI for the detection of atherosclerosis 10, 16, 17). The results of CAVI measurements have been reported in patients with various cardiovascular risk factors, such as obesity, metabolic syndrome and essential hypertension 15, 18) ; however, there is very limited information on CAVI in patients with dyslipidaemia (DLP) 14). Aim The aim of this study was to evaluate whether CAVI differs in dyslipidaemic subjects with and without the main cardiovascular risk factors: hypertension, diabetes mellitus and smoking. Methods Patient Groups The studied population consisted of 392 subjects (166 men, 226 women) aged 18 years and above (median age of 58.5 and 5-95 percentile range years), with DLP. The patients were followed up in the Outpatients Department of Preventive Cardiology and underwent regular check-up examinations between January 2010 and November DLP was defined by any of the following parameters: total cholesterol >5.0 mmol/l, LDL-cholesterol >3.0 mmol/ L, triglycerides >1.7 mmol/l, HDL-cholesterol <1.2 mmol/l (women) or <1.0 mmol/l (men), or hypolipidaemic drug treatments. In all subjects, the main causes of secondary DLP (e.g. hypothyroidism, renal disease, uncontrolled diabetes mellitus, liver disease, and alcoholism) were excluded. Diagnosis of diabetes mellitus was made if the concentration of venous plasma glucose was 7.0 mmol/l or if antidiabetic drugs were used. Hypertension was defined as systolic blood pressure (BP) 140 torr or/and diastolic BP 90 torr or use of antihypertensive drugs. All currently smoking patients (regardless of the number of cigarettes) were considered as smokers; former smokers were patients who had smoked in the past and non-smokers were patients who had never smoked at all. All patients with manifested atherosclerotic disease (previous stroke or transient ischemic attack, previous angina pectoris or myocardial infarction, documented chronic ischemic heart disease, peripheral artery disease, cardiomyopathy or significant valvular disease, arrhythmia and also patients with heart failure) were excluded from the study. All subjects in this study were Caucasian and of Slavic origin. The study complied with the Declaration of Helsinki and was approved by the Ethics Committee of St. Anne s Faculty Hospital Brno. Written informed consent was obtained from the study participants at the beginning of the study. Anthropometric Indices Height and weight were measured by trained medical staff; BMI was calculated as weight (kg)/ height squared (m 2 ). Biomedical Markers Blood pressure was measured twice (in a sitting position): once in the waiting room upon arrival and again after at least 10 minutes of rest, and the mean was calculated. Blood samples for lipid and glucose analysis were taken in the morning after 8-10 hours of

3 CAVI in Subjects with Dyslipidaemia 445 fasting and they were sent for analysis to the laboratory within half an hour after collection. All laboratory tests were carried out in the same laboratory. Lipids and lipoprotein analyses were performed on the Modular SWA P300 analyser (Roche, Basel, Switzerland) with commercially available kits: total cholesterol and triglycerides were assayed by the enzymatic colorimetric method (Roche Diagnostic GmBH), HDL-cholesterol by the homogenous method for direct measuring without precipitation (Sekisui Medical, Tokyo), and apolipoprotein B by immunoturbidimetric assay. LDL-cholesterol was calculated according to the Friedewald equation 19). CAVI Measurement CAVI was measured using the system VaSera 1500 (Fukuda Denshi Co.), adopting the oscillometric method for blood pressure measurement. It does not measure BP in the 4 limbs simultaneously but first measures BP at the right brachial and ankle and then at the left brachial and ankle. Thus, arteries on the right and left sides are pressurized alternately with the other side open. This procedure does not only reduce the burden on examinees but also enables more accurate measurement. The CAVI calculation is based on stiffness parameter β obtained by means of the Bramwell-Hill equation 9, 20) : CAVI=(InPs/Pd) 2ρ/ΔP PWV 2, where Ps and Pd are the systolic and diastolic blood pressure, respectively, PWV is the pulse wave velocity between the heart and ankle, ρ is blood density, and ΔP is pulse pressure. CAVI was measured by trained medical staff, with the participant resting in a supine position and the head held in the midline position. ECG and phonocardiography were monitored during the measurement. In order to limit the effect of diurnal variations, all subjects were always examined at the same time, between 8:00-11:00 AM. The examination was conducted in a quiet room and at a stable temperature of Statistics Standard summary statistics were used to describe primary data; 5th and 95th percentiles for continuous variables; absolute and relative frequencies for categorical variables. Statistical significance of differences between/among groups was assessed using the Mann-Whitney U test or the Kruskal-Wallis test for continuous parameters, respectively. For evaluation of the relationship between selected variables and CAVI, Spearman s rank correlation coefficient was applied. All analyses were computed for primary CAVI data Table 1. Basic characteristics of patients n=392 Description Age (years) Body mass index (kg/m 2 ) Waist (cm) Systolic BP (mmhg) Diastolic BP (mmhg) Hypertension Diabetes mellitus Smoking Total cholesterol (mmol/l) HDL-cholesterol (mmol/l) LDL-cholesterol (mmol/l) Triglycerides (mmol/l) Apolipoprotein B (g/l) 58.5 ( ) 26.9 ( ) 92.0 ( ) ( ) 82.5 ( ) 154 (39.3%) 52 (13.3%) 110 (28.1%) 5.81 ( ) 1.36 ( ) 3.48 ( ) 1.55 ( ) 1.00 ( ) BP: blood pressure; continuous variables are described using the median and 5th-95th percentile range, categorical variables are described by their absolute frequencies and percentage and for CAVI values adjusted for age and gender. Linear regression modelling CAVI dependence on age and gender was used for the adjustment. The level of statistical significance was set as α= 0.05 for all analyses. Data analyses were performed by IBM SPSS 19 for Windows (Release , IBM Corporation 2010). Results Basic characteristics of the studied population (patients with DLP) are summarized in Table 1. The median age was 58.5 years (5-95 percentile range years), BMI was in the overweight range and there were 28.1 % smokers and 13.3% of patients with diabetes mellitus. Of 52 patients with diabetes, 2 suffered from type Ⅰ diabetes mellitus (treated by insulin), 50 from type Ⅱ diabetes; 38 type Ⅱ diabetics (76%) were treated with peroral antidiabetics, 3 were treated with a combination of peroral antidiabetics and insulin and 9 patients were not treated at all. The studied population further included 154 patients with hypertension, of whom 146 (95%) were treated with antihypertensive drugs. Sixty-five patients used monotherapy, 48 were treated by a combination of two compounds, 30 by three and 3 patients by four drugs. The following antihypertensive drugs were used: ACE inhibitors were used by 67 patients, Ca channel blockers by 51 patients, beta-blockers by 40, ARB (sartans) by 39, diuretics by 24, and central antihypertensives by 12 patients. Most subjects (60.5%) were treated with statins, and therefore total cholesterol and LDL-cholesterol was only slightly elevated,

4 446 Soska et al. Table 2. Difference in gender, age, CAVI and adjusted CAVI according to selected groups of patients Total (n =392) N Men/Women Age CAVI Adjusted CAVI, Hypertension No Yes p Diabetes mellitus No Yes p Smoking No Yes FS p Statins No Yes p (40.3%)/142 (59.7%) 70 (45.5%)/84 (54.5%) (40.6%)/202 (59.4%) 28 (53.8%)/24 (46.2%) (36.9%)/178 (63.1%) 36 (53.7%)/31 (46.3%) 26 (60.5%)/17 (39.5%) * 77 (49.7%)/78 (50.3%) 89 (37.6%)/148 (62.4%) * 56.0 ( ) 60.9 ( ) 58.1 ( ) 59.1 ( ) ( ) 55.8 ( ) 56.5 ( ) ( ) 61.3 ( ) 8.15 ( ) 8.70 ( ) 8.30 ( ) 8.30 ( ) ( ) 8.30 ( ) 8.35 ( ) ( ) 8.65 ( ) 8.26 ( ) 8.27 ( ) ( ) 8.12 ( ) ( ) 8.38 ( ) 8.46 ( ) 8.18 ( ) 8.32 ( ) CAVI: cardio-ankle vascular index; FS: former smokers; adjusted for age and gender; continuous variables are described using the median and 5th-95th percentile, categorical variables are described by their absolute and relative frequencies; statistical significance of difference in continuous variables tested by the Mann-Whitney U test or Kruskal-Wallis test, statistical significance of difference between categorical variables tested by the maximum likelihood Chi-squared test; * statistically significant CAVI R = p < 0.001* Age Fig.1. Correlation between CAVI and age (Spearman s rank correlation coefficient). CAVI: cardio-ankle vascular index; r: Spearman s rank correlation coefficient statin dose was 32 mg/day. Differences in gender, age and CAVI according to selected groups of patients are overviewed in Table 2. Significantly higher CAVI values were found in subjects with hypertension than in normotensive suband HDL-cholesterol, triglycerides and apolipoprotein B were in reference ranges (Table 1). Out of the total number of patients treated with statins (237), 124 (52%) used atorvastatin, 70 (30%) simvastatin, 24 (10%) rosuvastatin, and 19 (8%) fluvastatin. Average

5 CAVI in Subjects with Dyslipidaemia p=0.064 p=0.034* p= th percentile Median 5 th percentile CAVI M (N=96) 55 yrs W (N=55) M (N=53) W (N=94) M (N=17) yrs > 65 yrs W (N=77) Fig.2. CAVI according to gender. CAVI: cardio-ankle vascular index; M: men; W: women jects (p<0.001), but the hypertensive group was older than the normotensive group (p<0.001). There was no significant difference in CAVI among smokers, previous smokers and non-smokers (p =0.217) and no differences in CAVI were observed between subjects with or without diabetes mellitus (p=0.424) (Table 2). When CAVI in the groups with and without statin treatment was compared, a significantly higher value was found in patients treated with statins (p<0.001). A statistically significant correlation of CAVI with age (p<0.001) was found (Fig.1). As the men and women differed statistically significantly in age (median age 52.9 and 61.8, respectively, p<0.001), CAVI relationship to gender was analysed within the age groups (Fig.2). CAVI values were higher in men then in women in all age groups; however, a statistically significant difference was found only in the age group (p =0.034). Based on these results, the linear regression adjustment of CAVI for age and gender as predictors was computed. Age- and gender-adjusted CAVI values did not differ in selected groups of patients: with or without hypertension, diabetes mellitus, treated or untreated with statins (Table 2). Adjusted CAVI values were significantly higher in smokers than no-smokers (former smokers) (p<0.001). No significant correlation was found between age- and gender-adjusted CAVI and blood lipids and lipoproteins (total cholesterol, LDLcholesterol, HDL-cholesterol, triglycerides, and apoli- poprotein B) (Table 3); however, age- and genderadjusted CAVI correlated significantly with both systolic and diastolic blood pressure (p<0.001). Discussion It is well known that the progression of atherosclerosis is accelerated in patients with DLP, hypertension and diabetes mellitus in comparison to the healthy population, particularly when two or more risk factors are present. A new approach for the noninvasive diagnosis of atherosclerosis is the measurement of CAVI, which essentially represents stiffness of the aorta, femoral artery and tibial artery as a whole 13). It has been reported that CAVI is a sensitive index of preclinical and clinical atherosclerosis 15, 17, 21) that may imply also progression of carotid and coronary arteriosclerosis 10, 16). Thus, the aim of this study was to evaluate whether the CAVI value in patients with DLP depends on the presence (or lack) of other cardiovascular risk factors: diabetes mellitus, hypertension, and smoking. In our data set, CAVI values significantly increased in DLP patients with hypertension as compared to normotensive patients; however, hypertensive group members were older than those in the group without hypertension, and CAVI is an age-dependent parameter 7, 22). It has been reported that CAVI of healthy men increased almost linearly with age from 20 to 70 years 23) ; a positive correlation between CAVI

6 448 Soska et al. Table 3. Correlation between CAVI, adjusted CAVI and selected variables n=458 CAVI Adjusted CAVI Spearman correlation coefficient/significance Spearman correlation coefficient/significance Systolic BP Diastolic BP Total cholesterol HDL-cholesterol LDL-cholesterol Triglycerides Apolipoprotein B 0.337/ 0.204/ 0.350/ 0.051/ / 0.036/ / 0.175/ 0.156/0.002 * 0.072/ / / / /0.760 CAVI: cardio-ankle vascular index; BP: blood pressure; adjusted for age and gender and age was also confirmed in this study. Concerning gender differences, Shirai (23) has proven that CAVI values are higher in men than in woman. As there was a different age structure of men and women in our set of patients, the CAVI relationship to gender within age groups was analysed. Higher CAVI values in men than women were confirmed, but this difference was statistically significant only in the age group. Due to age and sex CAVI differences, the adjustment model included both age and gender in order to achieve the best possible removal of influence of these confounding factors. After this adjustment, CAVI values did not differ significantly between hypertensive and normotensive subjects. As far as the relationship between CAVI and blood pressure is concerned, several authors have reported that CAVI correlates significantly with blood pressure 13, 23). On the other hand, CAVI is not affected by blood pressure at the time of measurement, so these studies demonstrated the real correlation between blood pressure itself and arterial wall stiffness 14, 15, 23, 24). Our study confirmed a significant correlation between CAVI and both systolic and diastolic blood pressure, but significant differences in age- and gender-adjusted CAVI between subjects with and without hypertension were not found. Similar results were reported by Ibata 25), who showed that, after multiple regression analysis, systolic blood pressure was not a significant risk factor of increased CAVI. This apparent discrepancy may be explained in two ways: a) CAVI is not affected by the actual value of blood pressure, but it is affected by changes in the contractility of smooth muscle cells in the vascular wall 26) ; b) CAVI can be decreased by certain antihypertensive drugs. Decreased CAVI has been reported, for example, after antagonists of angiotensin Ⅱ receptor (sartanes) and after calcium channel blockers, in monotherapy as well as in combination with a diuretic drug, hydrochlorthiasid 27-30). In this study, 95% hypertensive patients were treated with antihypertensives, of which 74% used sartanes, Ca channel blockers or diuretics. This may result in CAVI, after adjustment for age and gender, not differing significantly between patients with and without hypertension. An important risk factor for premature atherosclerosis is also diabetes mellitus. It has been reported that CAVI is increased in patients with diabetes mellitus and that there is a relationship between increased CAVI and HbA1c 25). Increased CAVI has been found in Japanese patients with metabolic syndrome 31) and, among hemodialysed patients, those with diabetes mellitus had a significantly higher CAVI than patients without diabetes 13). However, in our set of Czech patients with DLP, we did not find increased CAVI in DLP patients with diabetes mellitus as compared to those without diabetes. When interpreting these results, it is necessary to take into consideration that CAVI in diabetic patients may be affected also by glucose-lowering drugs, which decrease CAVI 32, 33). In our set of patients, 77% of those with diabetes mellitus were treated with glucose-lowering drugs. This may explain why CAVI in our group of diabetic patients did not differ significantly from CAVI in the group of non-diabetic patients. Smoking is another important risk factor for premature atherosclerosis and it has been reported that CAVI could reflect the smoking status: CAVI was increased by smoking and complete smoking cessation improved CAVI 34). In this study we confirmed the previous results: CAVI in smokers was significantly higher than CAVI in non-smokers or former smokers, although smokers were younger than non-smokers and previous smokers. Another well-known risk factor for premature atherosclerosis is DLP, primarily a high level of LDL

7 CAVI in Subjects with Dyslipidaemia 449 References 1) Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R; Cholesterol Treatment Trialists (CTT) Collaborators: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet, 2005; 366: ) Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN; REVERSAL Investigators: Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA, 2004; 291: ) Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE: Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 1997; 96: ) Chambless LE, Folsom AR, Clegg LX, Sharrett AR, Shahar E, Nieto FJ, Rosamond WD, Evans G: Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol, 2000; 151: ) van Popele NM, Grobbee DE, Bots ML, Asmar R, Topouchian J, Reneman RS, Hoeks AP, van der Kuip DA, Hofman A, Witteman JC: Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke, 2001; 32: ) Munakata M, Sakuraba J, Tayama J, Furuta T, Yusa A, Nunokawa T, Yoshinaga K, Toyota T: Higher brachialankle pulse wave velocity is associated with more advanced carotid atherosclerosis in end-stage renal disease. Hypercholesterol. DLP was present in all subjects in our study group, but 60.5% of subjects were treated with statins, so the concentration of total cholesterol (5.81 mmol/l) and LDL cholesterol (3.48 mmol/l) was only slightly increased as compared with reference levels; triglycerides (1.55 mmol/l), HDL cholesterol (1.36 mmol/l) and apolipoprotein B (1.00 g/l) concentration were within reference values. Significantly higher CAVI values were found in subjects with DLP treated with statins in comparison with those without statin therapy, but the statin-treated subgroup was older and age- and gender-adjusted CAVI did not differ significantly. No significant correlation between CAVI and blood lipids and lipoproteins (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and apolipoprotein B) was found. DLP and CAVI are probably not closely connected and DLP per se does not immediately increase arterial wall stiffness. Takaki 14) reported that CAVI had a poor relationship with total cholesterol and LDL-cholesterol levels and there was no correlation among CAVI and the triglyceride and HDL-cholesterol levels observed. Higashiyama 35) reported recently that in patients without cardiovascular disorders with moderately increased LDLcholesterol, CAVI correlates better with the high-sensitivity C-reactive protein (hs-crp) value than with the LDL-cholesterol level. The highest CAVI was found in the group of patients with increased LDLcholesterol as well as hs-crp. Moreover, CAVI in patients with dyslipidaemia may be influenced also by treatment with hypolipidaemics 36, 37). It has been reported that statins decrease CAVI and improve arterial stiffness in patients with coronary artery disease and hyperlipidaemia 38, 39). In our study, 65% of patients were treated with statins, which might decrease the average CAVI value. Lipid-lowering therapy with statins in our set of patients was sufficient since average values of total cholesterol as well as LDL-cholesterol were close to the average values in the Czech population. According to the results of the Czech post-monica study, the average values of total cholesterol and LDL-cholesterol in the Czech Republic in were 5.3 and 3.2 mmol/l 40). There are several limitations of this study. First, the study was not designed as a case-control study; therefore, the subjects with and without risk factors were not age- and sex-matched. Nevertheless, adjustment for age and sex is a well-accepted statistical approach to overcoming differences between study and control populations. Secondly, it was not possible to evaluate the direct effect of treatment with statins, antihypertensive drugs and glucose-lowering drugs on CAVI, since treatment with these substances was introduced much earlier than the measurement of CAVI and discontinuation of treatment before CAVI measurement for a longer time was impossible for ethical reasons; however, the aim of this study was to assess CAVI values in routinely treated DLP subjects with and without other risk factors. Thirdly, when interpreting our results it must be taken into consideration that CAVI essentially represents stiffness of the aorta, femoral artery and tibial artery as a whole 13) ; thus, stiffness of other arteries might not be always manifested as CAVI change. In conclusion, in our set of patients we demonstrated that the CAVI value in treated DLP patients is not significantly affected by hypertension and diabetes mellitus, but is increased by smoking; however, further studies using clinical long-term follow-up and casecontrol studies are required. Disclosure The authors declare no conflicts of interest.

8 450 Soska et al. tens Res, 2005; 28: ) Tomiyama H, Koji Y, Yambe M, Shiina K, Motobe K, Yamada J, Shido N, Tanaka N, Chikamori T, Yamashina A: Brachial ankle pulse wave velocity is a simple and independent predictor of prognosis in patients with acute coronary syndrome. Circ J, 2005; 69: ) Imanishi R, Seto S, Toda G, Yoshida M, Ohtsuru A, Koide Y, Baba T, Yano K: High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men. Hypertens Res, 2004; 27: ) Yambe T, Yoshizawa M, Saijo Y, Yamaguchi T, Shibata M, Konno S, Nitta S, Kuwayama T: Brachio-ankle pulse wave velocity and cardio-ankle vascular index (CAVI). Biomed Pharmacother, 2004; 58: S95-S98 10) Izuhara M, Shioji K, Kadota S, Baba O, Takeuchi Y, Uegaito T, Mutsuo S, Matsuda M: Relationship of cardioankle vascular index (CAVI) to carotid and coronary arteriosclerosis. Circ J, 2008; 72: ) Kubozono T, Miyata M, Ueyama K, Nagaki A, Otsuji Y, Kusano K, Kubozono O, Tei C: Clinical Significance and Reproducibility of New Arterial Distensibility Index. Circ J, 2007; 71: ) Huck CJ, Bronas UG, Williamson EB, Draheim CC, Duprez DA, Dengel DR: Noninvasive measurements of arterial stiffness: repeatability and interrelationships with endothelial function and arterial morphology measures. Vasc Health Risk Manag, 2007; 3: ) Shirai K, Utino J, Otsuka K, Takata M: A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb, 2006; 13: ) Takaki A, Ogawa H, Wakeyama T, Iwami T, Kimura M, Hadano Y, Matsuda S, Miyazaki Y, Matsuda T, Hiratsuka A, Matsuzaki M: Cardio-ankle vascular index is a new noninvasive parameter of arterial stiffness. Circ J, 2007; 71: ) Okura T, Watanabe S, Kurata M, Manabe S, Koresawa M, Irita J, Enomoto D, Miyoshi K, Fukuoka T, Higaki J: Relationship between cardio-ankle vascular index (CAVI) and carotid atherosclerosis in patients with essential hypertension. Hypertens Res, 2007; 30: ) Miyoshi T, Doi M, Hirohata S, Sakane K, Kamikawa S, Kitawaki T, Kaji Y, Kusano KF, Ninomiya Y, Kusachi S: Cardio-ankle vascular index is independently associated with the severity of coronary atherosclerosis and left ventricular function in patients with ischemic heart disease. J Atheroscler Thromb, 2010; 17: ) Yambe T, Meng X, Hou X, Wang Q, Sekine K, Shiraishi Y, Watanabe M, Yamaguchi T, Shibata M, Kuwayama T, Maruyama M, Konno S, Nitta S: Cardio-ankle vascular index (CAVI) for the monitoring of the atherosclerosis after heart transplantation. Biomed Pharmacother, 2005; 59: S177-S179 18) Satoh N, Shimatsu A, Kato Y, Araki R, Koyama K, Okajima T, Tanabe M, Ooishi M, Kotani K, Ogawa Y: Evaluation of the cardio-ankle vascular index, a new indicator of arterial stiffness independent of blood pressure, in obesity and metabolic syndrome. Hypertens Res, 2008; 31: ) Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem, 1972; 18: ) Bramwell JC, Hill AV: Velocity of the pulse wave in man. Proc Roy Soc B, 1922; 93: ) Wakabayashi I, Masuda H: Effects of age on the relationship between cardio-ankle vascular index and atherosclerotic progression in patients with type 2 diabetes mellitus. Nippon Ronen Igakkai Zasshi, 2006; 43: ) Dobsak P, Sosikova M, Dusek L, Soucek M, Novakova M, Yambe T, Wolf J-E, Vitovec J, Spinarova L, Soska V, Fiser B, Siegelova J: Arterial stiffness in Czech population measured by VASERA Scripta Medica, 2010; 83: ) Shirai K, Hiruta N, Song M, Kurosu T, Suzuki J, Tomaru T, Miyashita Y, Saiki A, Takahashi M, Suzuki K, Takata M: Cardio-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: theory, evidence and perspectives. J Atheroscler Thromb, 2011; 18: ) Kadota K, Takamura N, Aoyagi K, Yamasaki H, Usa T, Nakazato M, Maeda T, Wada M, Nakashima K, Abe K, Takeshima F, Ozono Y: Availability of cardio-ankle vascular index (CAVI) as a screening tool for atherosclerosis. Circ J, 2008; 72: ) Ibata J, Sasaki H, Kakimoto T, Matsuno S, Nakatani M, Kobayashi M, Tatsumi K, Nakano Y, Wakasaki H, Furuta H, Nishi M, Nanjo K: Cardio-ankle vascular index measures arterial wall stiffness independent of blood pressure. Diabetes Res Clin Pract, 2008; 80: ) Shirai K, Song M, Suzuki J, Kurosu T, Oyama T, Nagayama D, Miyashita Y, Yamamura S, Takahashi M: Contradictory Effects of beta 1-and alpha 1-Aderenergic Receptor Blockers on Cardio-Ankle Vascular Stiffness Index (CAVI) - CAVI is Independent of Blood Pressure. J Atheroscler Thromb, 2011; 18: ) Uehara G, Takeda H: Relative effects of telmisartan, candesartan and losartan on alleviating arterial stiffness in patients with hypertension complicated by diabetes mellitus: an evaluation using the cardio-ankle vascular index (CAVI). J Int Med Res, 2008; 36: ) Kinouchi K, Ichihara A, Sakoda M, Kurauchi-Mito A, Murohashi-Bokuda K, Itoh H: Effects of telmisartan on arterial stiffness assessed by the cardio-ankle vascular index in hypertensive patients. Kidney Blood Press Res, 2010; 33: ) Sasaki H, Saiki A, Endo K, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohhira M, Oyama T, Miyashita Y, Shirai K: Protective effects of efonidipine, a T- and L-type calcium channel blocker, on renal function and arterial stiffness in type 2 diabetic patients with hypertension and nephropathy. J Atheroscler Thromb, 2009; 16: ) Kinouchi K, Ichihara A, Sakoda M, Kurauchi-Mito A, Itoh H: Safety and benefits of a tablet combining losartan and hydrochlorothiazide in Japanese diabetic patients with hypertension. Hypertens Res, 2009; 32: ) Satoh N, Shimatsu A, Kato Y, Araki R, Koyama K, Okajima T, Tanabe M, Ooishi M, Kotani K, Ogawa Y: Evaluation of the cardio-ankle vascular index, a new indicator of arterial stiffness independent of blood pressure, in obesity and metabolic syndrome. Hypertens Res, 2008; 31:

9 CAVI in Subjects with Dyslipidaemia ) Nagayama D, Saiki A, Endo K, Yamaguchi T, Ban N, Kawana H, Ohira M, Oyama T, Miyashita Y, Shirai K: Improvement of cardio-ankle vascular index by glimepiride in type 2 diabetic patients. Int J Clin Pract, 2010; 64: ) Ohira M, Endo K, Oyama T, Yamaguchi T, Ban N, Kawana H, Nagayama D, Nagumo A, Saiki A, Murano T, Watanabe H, Miyashita Y, Shirai K: Improvement of postprandial hyperglycemia and arterial stiffness upon switching from premixed human insulin 30/70 to biphasic insulin aspart 30/70. Metabolism, 2011; 60: ) Noike H, Nakamura K, Sugiyama Y, Iizuka T, Shimizu K, Takahashi M, Hirano K, Suzuki M, Mikamo H, Nakagami T, Shirai K: Changes in cardio-ankle vascular index in smoking cessation. J Atheroscler Thromb, 2010; 17: ) Higashiyama A, Wakabayashi I, Kubota Y, Adachi Y, Hayashibe A, Nishimura K, Sugiyama D, Kadota A, Imano H, Miyamatsu N, Miyamoto Y, Okamura T: Does High-Sensitivity C-Reactive Protein or Low-Density Lipoprotein Cholesterol Show a Stronger Relationship with the Cardio-Ankle Vascular Index in Healthy Community Dwellers?: the KOBE Study. J Atheroscler Thromb, 2012; 19: ) Miyashita Y, Endo K, Saiki A, Ban N, Nagumo A, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K: Effect of ezetimibe monotherapy on lipid metabolism and arterial stiffness assessed by cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb, 2010; 17: ) Soska V, Dobsak P, Dusek L, Shirai K, Jarkovsky J, Novakova M, Brhel P, Stastna J, Fajkusova L, Freiberger T, Yambe T: Cardio-ankle vascular index in heterozygous familial hypercholesterolemia. J Atheroscler Thromb, 2012; 19: ) Hongo M, Tsutsui H, Mawatari E, Hidaka H, Kumazaki S, Yazaki Y, Takahashi M, Kinoshita O, Ikeda U: Fluvastatin improves arterial stiffness in patients with coronary artery disease and hyperlipidemia: a 5-year follow-up study. Circ J, 2008; 72: ) Miyashita Y, Endo K, Saiki A, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K: Effects of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb, 2009; 16: ) Cifkova R, Bruthans J, Adamkova V, Jozifova M, Galovcova M, Wohlfart P, Krajcoviechova A, Petrzilkova Z, Lanska L, Poledne R, Stavek P: The prevalence or major cardiovascular risk factors in the Czech population in The post-monica study. Cor Vasa, 2011; 53: 1-10