Vascular Compliance is Reduced in Geriatric People with Angiographic Coronary Atherosclerosis

The Journal of International Medical Research 2009; 37: 1443 1449 Vascular Compliance is Reduced in Geriatric People with Angiographic Coronary Atherosclerosis B-A YOU 1, H-Q GAO 1, G-S LI 2, X-Y HUO 1 AND L-Y QIE 1 1 Department of Geriatrics, and 2 Department of Cardiology of Qilu Hospital, Shandong University, Jinan, China This study investigated the value of arterial elasticity measurement in the early diagnosis of angiographic coronary artery atherosclerosis in 105 consecutive elderly patients. They were divided into two groups according to the results of selective coronary angiography: 55 with coronary atherosclerosis and 50 with a normal coronary angiogram. The Gensini score of the coronary artery was acquired and capacitive arterial compliance (C1) and oscillatory arterial compliance (C2) were measured. An independent-sample t- test was used to evaluate the difference in C1 and C2 between the two groups. Bivariate analyses were performed to study the association between the Gensini score and C1 and C2. A significant difference between the two groups in C2 was found and the Gensini score of the coronary artery was significantly correlated with C2. Identification of early coronary atherosclerosis in geriatrics may be aided by the prognostic value of C2. KEY WORDS: CORONARY ANGIOGRAPHY; CORONARY ARTERY ATHEROSCLEROSIS; GERIATRIC; GENSINI SCORE; CAPACITIVE ARTERIAL COMPLIANCE; OSCILLATORY ARTERIAL COMPLIANCE; VASCULAR COMPLIANCE; ELASTICITY Introduction Cardiovascular (CV) disease resulting from arteriosclerosis is a serious worldwide health risk. 1,2 Early diagnosis and intervention in vascular disease is important to control adverse CV events, such as acute myocardial infarction, stroke and cardiac death. 3 Elasticity is an important characteristic of the arteries and a direct reflection of the condition of these blood vessels, and reduced arterial elasticity is a sensitive marker that indicates damage to the blood vessel wall. 4,5 It has been reported that capacitive arterial compliance (C1) and oscillatory arterial compliance (C2) can accurately reflect arterial elasticity. 6,7 It has also been noted that the compliance of small arteries, defined as the change in volume per unit of pressure ( V/ P) and which reflects the buffering function of the vessel, 8 is lower in post-menopausal women with symptomatic coronary artery disease (CAD) than in those without CAD. 9 Small artery compliance also reflects subtle vascular alterations due to ageing, 10 hypertension, 9 and type 1 diabetes, 11 and is gender dependent female subjects have been observed to have lower small artery compliance than male subjects. 12 It has been 1443

shown that a lower small artery compliance is associated with diffuse-cad. 13 Small artery compliance appears, therefore, to be a useful tool for the clinical screening of individuals of CAD. Few studies, however, have investigated the changes in small artery compliance in geriatrics with angiographic coronary atherosclerosis prior to CAD. This study was designed to investigate whether small artery compliance was reduced in elderly people with angiographic coronary atherosclerosis before they were diagnosed with CAD. Patients and methods PATIENT POPULATION In this retrospective, observational study, consecutive elderly patients, aged 65 years, were selected from those who had undergone selective coronary angiography at Qilu Hospital, Shandong University, Jinan, China, between October 2007 and October 2008. The selected patients were divided into two groups according to the results of selective coronary angiography: those with normal coronary angiogram and those diagnosed as having coronary atherosclerosis. Coronary atherosclerosis was defined as luminal stenosis > 0% but < 50% (lumen diameter reduction) of major vessels in the coronary arterial tree, and normal coronary angiogram was defined as 0% stenosis of the coronary artery lumen. Patients with arteriosclerosis obliterans, valvular heart disease, arrhythmia, or heart failure were excluded because of potential inaccuracy in pulse wave recording and analysis. All patients in the study provided verbal informed consent. The study protocol was approved by the Ethics Board of Qilu Hospital, Shandong University. MEDICAL HISTORY AND EXAMINATIONS All patients were administered a standardized questionnaire for the acquisition of information about their occupation, medical history, drug use, smoking history and family medical history. In a quiet room, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were measured using a CVProfilor DO-2020 cardiovascular profiling system (Hypertension Diagnostics, Eagan, MN, USA) on the right arm while patients were in a seated position after resting for at least 5 min. The SBP, DBP and MAP for each patient were measured three times, with a 5-min interval between each measurement, and the mean of these measurements was calculated. Pulse pressure (PP) was calculated from the difference between SBP and DBP. Body mass index (BMI) was calculated as weight (kg) divided by the square of the height (m). Levels of total cholesterol (TC), triglyceride (TG) and fasting plasma glucose (FPG) were measured from fasting venous blood samples by local automated facilities. None of the patients had smoked, or drunk alcohol or coffee within 1 h of these examinations. C1 AND C2 MEASUREMENTS Measurement of C1 and C2 was carried out three times, with a 5-min interval between each measurement, using a CVProfilor DO- 2020 system and the mean of these measurements was calculated. The detector of the instrument was placed on the right radial artery of each patient in the supine position for an ideal pulse wave and the strongest signal. Then, radial artery waveforms were recorded for 30 s and digitized at 200 samples/s. The instrument automatically analysed the pulse wave data to obtain values for C1 and C2. To obtain a measure of arterial compliance, a modified Windkessel model was used that divided total systemic arterial compliance into large 1444

artery (capacitive) and small artery (oscillatory) compliance. 10 The model describes DBP contours by the following equation: P(t) = A 1e A 2t + A 3e A 4t cos(a 5t + A 6 ), where P(t) is the diastolic pressure at time t relative to aortic valve closure. A parameter-estimating algorithm determined the best set of values (A i ) for matching the diastolic portion of the measured beat to this equation. These A i parameters, together with an estimate of systemic vascular resistance, determined the C1 and C2 values. ASSESSMENT OF CORONARY ATHEROSCLEROSIS BY QCA Selective coronary angiography was performed according to standard clinical practice, with radial or femoral approaches using catheters 6F or greater in size to facilitate subsequent quantitative coronary angiographic (QCA) analysis. A computerbased edge-detection coronary angiography analysis system was used to perform QCA analyses. Coronary angiograms were obtained in multiple views matched after intracoronary injection of nitrates. Angiographic scoring was performed by observers who were blinded to the arterial elasticity and whose only involvement in the study was scoring the angiograms. The severity of coronary atherosclerosis was assessed using the Gensini score, 14 which was computed by assigning a severity score to each coronary stenosis according to geographic importance and the degree of luminal narrowing. STATISTICAL ANALYSES All data analyses were performed using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA) for Windows. Quantitative data were expressed as mean ± SD. Categorical data were presented as numbers and percentages. An independent-sample t-test was used to compare continuous data and the χ 2 -test was used to compare categorical variables between the two groups. Bivariate analyses were performed to study associations between coronary artery Gensini score and each of C1 and C2. A P-value < 0.05 was considered to be statistically significant. Results The study population comprised 105 consecutive elderly patients, aged 65 years, selected from 818 patients who underwent selective coronary angiography in Qilu Hospital, Shandong University between October 2007 and October 2008. Of these 105 patients, 55 had coronary atherosclerosis and 50 had a normal coronary angiogram. Their clinical data are shown in Table 1. There were no significant differences between the two groups for any of the demographic or clinical characteristics measured. Angiographic results gave a Gensini score of 0 in the normal coronary angiogram group whereas, among the 55 patients with coronary atherosclerosis, the minimum Gensini score was 1 and the maximum was 12. Independent-sample t-test analysis demonstrated a significant difference in C2 between the coronary atherosclerosis group and the normal coronary angiogram group (P = 0.006), but there was no significant difference in C1 (Table 2). Bivariate analysis between the Gensini score and C2 in the 55 patients of the coronary atherosclerosis group showed a negative correlation (r = 0.566, P < 0.01; Fig. 1). There was no significant correlation between Gensini score and C1 (r = 0.054; data not shown). Discussion Numerous instruments can be used to assess 1445

TABLE 1: Clinical characteristics of the 105 consecutive geriatric subjects selected from patients who underwent selective coronary angiography Normal coronary Coronary angiogram group atherosclerosis Statistical (n = 50) group (n = 55) significance Gender (male/female) 29/21 37/18 NS Age (years) 68.40 ± 2.98 69.34 ± 3.73 NS BMI (kg/m 2 ) 24.60 ± 3.48 25.42 ± 2.69 NS SBP (mmhg) 125.24 ± 10.17 125.56 ± 11.27 NS DBP (mmhg) 73.00 ± 9.01 70.38 ± 8.84 NS PP (mmhg) 52.24 ± 9.79 51.09 ± 9.61 NS MAP (mmhg) 90.10 ± 8.18 88.51 ± 7.60 NS HR (beats/min) 72.90 ± 9.79 71.07 ± 10.11 NS TC (mmol/l) 4.29 ± 0.86 4.38 ± 0.88 NS TG (mmol/l) 1.76 ± 0.70 1.78 ± 0.59 NS FPG (mmol/l) 5.54 ± 0.88 5.64 ± 0.99 NS History of hypertension (yes/no) 18/32 26/29 NS History of DM (yes/no) 6/44 13/42 NS History of smoking (yes/no) 22/28 23/32 NS Family history of CAD (yes/no) 5/45 7/48 NS ACEIs or ARBs (yes/no) 10/40 15/40 NS β-blockers (yes/no) 11/39 16/39 NS CCBs (yes/no) 15/35 16/39 NS Statins (yes/no) 6/44 7/48 NS Data show mean ± SD or numbers of patients. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; MAP, mean arterial pressure; HR, heart rate; TC, total cholesterol; TG, triglyceride; FPG, fasting plasma glucose; DM, diabetes mellitus; CAD, coronary artery disease; ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; CCBs, calcium channel blockers; NS, not statistically significant (P > 0.05). arterial stiffness in a non-invasive manner. The CVProfilor DO-2020 system has already been utilized in many hospitals worldwide and has been shown to be effective at detecting arterial stiffness. 15 The C1 value mainly reflects elasticity of the large arteries, while C2 is an index for the elasticity of small arteries. 16 In addition to the observation by Syeda et al. 13 that small artery compliance is useful in identifying TABLE 2: Comparison of C1 and C2 between the coronary atherosclerosis group and the normal coronary angiogram group Normal coronary Coronary angiogram group atherosclerosis Statistical (n = 50) group (n = 55) significance C1 (ml/mmhg 10) 13.84 ± 2.86 13.88 ± 3.29 NS C2 (ml/mmhg 100) 6.71 ± 1.90 4.58 ± 1.53 P = 0.006 Data are mean ± SD. C1, capacitive arterial compliance; C2, oscillatory arterial compliance; NS, not statistically significant (P > 0.05). 1446

14 12 10 Gensini score 8 6 4 2 0 0 2 4 6 8 10 C2 (ml/mmhg x 10) FIGURE 1: Bivariate analysis between the Gensini score and oscillatory arterial compliance (C2) in the 55 patients of the coronary atherosclerosis group showed a significant negative correlation (r = 0.566, P < 0.01) patients with diffuse-cad, Takeuchi et al. 17 found that the small artery elasticity index (C2) was related to CAD in male hypertensive patients with and without controlling for age, diabetes mellitus, smoking or lipid-lowering drug treatment. The quantitative relationship between the severity of coronary atherosclerosis and C2 has not, however, been previously reported. In addition, it has not been reported whether changes occur in C1 and C2 in elderly patients with coronary artery atherosclerosis when there are no significant stenoses (< 50%) in the coronary artery. In the present study, the Gensini score of patients with coronary atherosclerosis ranged from 1 to 12, whereas the score in the normal coronary angiogram group was 0. Using the independent-sample t-test or χ 2 -test no significant differences were found between the two groups in basic clinical characteristics or in C1, but patients with coronary atherosclerosis had a statistically significantly lower C2 than those in the normal coronary angiogram group. Using bivariate analysis, a negative correlation was found between the Gensini score and C2. It can be concluded that C2 decreased in the early stages of coronary artery atherosclerosis in elderly patients when there were no significant stenoses in the coronary artery and may, therefore, have a prognostic value in diagnosing coronary atherosclerosis in elderly subjects. Structural alterations of the arterial wall are well known to precede atherosclerosis and cardiovascular events, and endothelial dysfunction appears to be the earliest marker for this structural change. 18 Some investigations have shown that reduced 1447

arterial compliance or elasticity provides an index to the structural abnormalities associated with ageing and disease states. 19,20 The present study confirmed that a reduction in C2 precedes the occurrence of CAD in elderly subjects and that reduced C2 could be an early marker in indicating the vascular abnormality that leads to coronary atherosclerosis or CAD. The measurement of arterial stiffness is non-invasive, relatively low cost, easy to use and acceptable to patients. 18 Although the prognostic value of this technology has been previously investigated, these studies have generally been small and performed in a limited number of at-risk groups. 18,21,22 Thus, where possible, this technology should now be incorporated into longitudinal studies so that the prognostic value of C2 can be fully defined. Various limitations apply to the present study. The QCA analyses were used to evaluate the severity of coronary atherosclerosis in all the enrolled patients in this study. QCA does not exclude extraluminal coronary plaque/atherosclerosis, so the normal control group in the present study may have included some coronary atherosclerosis patients, which would have caused a bias in the results. Secondly, other drugs, aside from those used in the present study, may influence arterial properties and should be investigated. Finally, the small sample size of the present study may have limited the power of this study, although it seems unlikely that a greater powered study would have detected a difference in C1 since the values were quite similar between the groups. Acknowledgements This study is a joint effort of many investigators and staff members whose contribution is gratefully acknowledged. We also thank the Department of Cardiology and the Department of Geriatrics of Qilu Hospital, Shandong University and, most importantly, the patients who participated in this study. Conflicts of interest The authors had no conflicts of interest to declare in relation to this article. Received for publication 16 April 2009 Accepted subject to revision 20 April 2009 Revised accepted 17 August 2009 Copyright 2009 Field House Publishing LLP References 1 Ballantyne C, Arroll B, Shepherd J: Lipids and CVD management: towards a global consensus. Eur Heart J 2005; 26: 2224 2231. 2 Ho WK, Hankey GJ, Eikelboom JW: Prevention of coronary heart disease with aspirin and clopidogrel: efficacy, safety, costs and costeffectiveness. Expert Opin Pharmacother 2004; 5: 493 503. 3 LaRosa JC: Chemoprevention of coronary atherosclerosis: the role of lipid interventions. A position paper of the American Council on Science and Health. MedGenMed 2002; 4: 12. 4 Oliver JJ, Webb DJ: Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. Arterioscler Thromb Vasc Biol 2003; 23: 554 566. 5 Kochkina MS, Zateishchikov DA, Sidorenko BA: Measurement of arterial stiffness and its clinical value. Kardiologiia 2005; 45: 63 71 [in Russian]. 6 Yambe M, Tomiyama H, Hirayama Y, et al: Arterial stiffening as a possible risk factor for both atherosclerosis and diastolic heart failure. Hypertens Res 2004; 27: 625 631. 7 Bhuiyan AR, Li S, Li H, et al: Distribution and correlates of arterial compliance measures in asymptomatic young adults: the Bogalusa Heart Study. Am J Hypertens 2005; 18(5 part 1): 684 691. 8 Van Bortel LM, Kool MJ, Boudier HA, et al: Effects of antihypertensive agents on local arterial distensibility and compliance. Hypertension 1995; 26: 531 534. 9 Cohn JN, Finkelstein S, McVeigh G, et al: Noninvasive pulse wave analysis for the early detection of vascular disease. Hypertension 1995; 26: 503 508. 1448

10 McVeigh GE, Bratteli CW, Morgan DJ, et al: Agerelated abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance. Hypertension 1999; 33: 1392 1398. 11 Romney JS, Lewanczuk RZ: Vascular compliance is reduced in the early stages of type 1 diabetes. Diabetes Care 2001; 24: 2102 2106. 12 Winer N, Sowers JR, Weber MA: Gender differences in vascular compliance in young, healthy subjects assessed by pulse contour analysis. J Clin Hypertens (Greenwich) 2001; 3: 145 152. 13 Syeda B, Gottsauner-Wolf M, Denk S, et al: Arterial compliance: a diagnostic marker for atherosclerotic plaque burden? Am J Hypertens 2003; 16(5 part 1): 356 362. 14 Gensini, GG: A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983; 51: 606 607. 15 Li B, Gao H, Li X, et al: Correlation between brachial-ankle pulse wave velocity and arterial compliance and cardiovascular risk factors in elderly patients with arteriosclerosis. Hypertens Res 2006; 29: 309 314. 16 Beltran A, McVeigh G, Morgan D, et al: Arterial compliance abnormalities in isolated systolic hypertension. Am J Hypertens 2001; 14: 1007 1011. 17 Takeuchi K, Zhang B, Ideishi M, et al: Influence of age and hypertension on the association between small artery compliance and coronary artery disease. Am J Hypertens 2004; 17: 1188 1191. 18 Tao J, Tu C, Wang Y, et al: Impaired endothelium-dependent vasodilation and arterial elasticity in patients with coronary artery disease. Zhonghua Xin Xue Guan Bing Za Zhi 2005; 33: 150 152 [in Chinese]. 19 Tomiyama H, Arai T, Koji Y, et al: The agerelated increase in arterial stiffness is augmented in phases according to the severity of hypertension. Hypertens Res 2004; 27: 465 470. 20 Benetos A, Adamopoulos C, Bureau JM, et al: Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period. Circulation 2002; 105: 1202 1207. 21 Kals J, Kampus P, Kals M, et al: Impact of oxidative stress on arterial elasticity in patients with atherosclerosis. Am J Hypertens 2006; 19: 902 908. 22 Duprez DA, De Buyzere MM, De Bruyne L, et al: Small and large artery elasticity indices in peripheral arterial occlusive disease (PAOD). Vasc Med 2001; 6: 211 214. Authors address for correspondence Dr Bei-An You Professor Hai-qing Gao Department of Geriatics, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong Province 250012, China. E-mails: youbeian@sina.com (Dr You); gaohaiqing52@yahoo.com.cn (Professor Gao) 1449