Published online before print October 25, 2007, doi: 10.1161/ATVBAHA.107.156950
© 2008 American Heart Association, Inc.
Clinical and Population Studies |
Arterial Stiffness Is Associated With Regional Ventricular Systolic and Diastolic Dysfunction
The Multi-Ethnic Study of Atherosclerosis
From the the Division of Cardiology (V.R.S.F., B.D.R., D.A.B., J.A.C.L.), Johns Hopkins University, Baltimore, Md; the Department of Radiology (J.F.P.), Tufts-New England Medical Center, Boston, Mass; the Division of Cardiovascular Medicine (S.C.), Brigham and Women’s Hospital, Harvard University, Boston, Mass; the Department of Biostatistics (B.C.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md; Cardiac Imaging (K.N.), Massachusetts General Hospital; the Department of Biostatistics (R.M.), University of Washington; the Department of Internal Medicine/Cardiology (G.H.), Wake Forest University Health Sciences, Winston-Salem, NC; the Department of Radiology (G.P.), Columbia University, New York; and Caritas Carney Hospital (D.H.O.), Department of Radiology (D.A.B., J.A.C.L.), Johns Hopkins University, Baltimore, Md.
Correspondence João A.C. Lima, MD, Division of Cardiology, Blalock 524, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21287-0409. E-mail jlima{at}jhmi.edu
Abstract
Objective— The pathophysiology of left ventricular (LV) dysfunction, particularly in the setting of a preserved ejection fraction (EF), remains unclear. Few studies have investigated the relationship between arterial compliance and LV function in humans, and none used cardiovascular MRI.
Methods and Results— We sought to determine whether arterial compliance is related to regional myocardial function among participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Arterial compliance was assessed using carotid ultrasound measurements to calculate the distensibility coefficient (DC) and Young’s modulus (YM). Circumferential systolic (SRS) and diastolic (SRE) strain rates were calculated by harmonic phase (HARP) from tagged MRI. Associations between arterial compliance and indices of ventricular function were adjusted for cardiovascular risk factors. We found a significant association between arterial compliance and SRS in all myocardial regions (P<0.05); arterial compliance was also associated with SRE in the lateral and septal wall regions (P<0.05). Multiple linear regression analyses demonstrated a direct linear relationship between the carotid artery DC and SRS across all LV segments and slices, even after adjustment for cardiovascular risk factors and LV mass. In regression analyses, a significant relationship between arterial compliance and SRE in the septal and antero-apical walls was also found and remained significant after multivariable adjustment.
Conclusion— Arterial stiffness is associated with early and asymptomatic impairment of systolic as well as diastolic myocardial function. Further studies are needed to elucidate role of vascular compliance in the development of ventricular dysfunction and failure.
We sought to determine whether or not arterial compliance is related to regional myocardial function among participants of the Multi-Ethnic Study of Atherosclerosis. We found a significant association between arterial compliance and regional myocardial function (SRS and SRE). Arterial stiffness is associated with early and asymptomatic impairment of regional myocardial function.
Key Words: arterial stiffness • regional ventricular function • heart failure • tagging MRI • strain rate
Heart failure (HF) continues to be a major cause of cardiovascular morbidity and mortality. Although the overall incidence of HF has stabilized, the prevalence of HF presenting in the setting of preserved ejection fraction (EF) is rising. x1Amid ongoing efforts to identify the mechanisms underlying myocardial dysfunction, recent work has focused on HF with preserved EF (HFPEF) in particular.2,3 There is now evidence to suggest that HFPEF is the product of an interplay between ventricular and vascular stiffening occurring with increasing age.4 This coupling of ventricular and vascular stiffening processes may lead to load-dependent impairment of systolic as well as diastolic ventricular function.5 To date, only a few studies have investigated the relationship between vascular compliance and ventricular structural6,7 or functional8,9 properties in humans. Furthermore, all previous work in this area has relied on Doppler echocardiography to assess ventricular indices. Cardiovascular magnetic resonance imaging (MRI) now offers a detailed assessment of intrinsic ventricular properties that can provide important complementary information to existing echocardiographic data. Therefore, we used carotid ultrasound in combination with cardiovascular MRI tissue tagging to examine the relationship between arterial compliance and ventricular function in a large cohort of ethnically diverse individuals free of known cardiovascular disease at baseline. Clarifying an association between decreased carotid arterial compliance and impaired ventricular function may further elucidate the pathogenesis of HF and, at the same time, highlight potential modalities for identifying subclinical ventricular dysfunction.
Methods
The Multi-ethnic Study of Atherosclerosis (MESA) design and population have been described in detail elsewhere.10 In brief, MESA is a prospective population-based observational cohort study of men and women from 4 different ethnic groups (Caucasian, African-American, Hispanic, and Chinese), aged 45 to 84 years old and free of clinical cardiovascular disease at baseline. In the MESA study, cardiac MRI was performed in 5004 participants as a part of the baseline examination. In this ancillary study, 1100 consecutive participants (53.8% male) underwent tagged MRI studies at enrollment in six centers (Wake Forest University, NC; Columbia University, NY; Johns Hopkins University, Md; University of Minnesota, Minn; Northwestern University, Ill; and University of California at Los Angeles, Calif). The participants for the tagged MRI study were randomly selected. This subcohort is similar to the MESA cohort in demographic aspects as previously described.11 All participants gave informed consent for the study protocol, which was approved by the institutional review boards of all MESA field centers as well as MRI and ultrasound reading centers.
MRI Protocol
Images were obtained using 1.5T MR scanners (SIGNA [LX and CVI], GE Medical Systems; and SIEMENS Medical Solutions [Vision and Sonata]) with ECG-triggered segmented k-space fast spoiled gradient-echo (SPGR or FLASH) pulse sequence during breath holds. Dedicated phase array coils were used for signal acquisition. After completing the standard imaging protocol, 3 tagged short axis slices were acquired at the LV base, mid-level, and apex. Parallel striped tags were ascribed in 2 orthogonal orientations (00 and 900) using identical pulse sequences with additional spatial modulation of magnetization (SPAMM).12 The parameters for tagged MRI images were: field of view 40 cm; slice thickness 8 to 10 mm; repetition time 3.5 to 7.2 ms; echo time 2.0 to 4.2 ms; flip angle 120; matrix size 256x96 to 140; 4 to 9 phase encoding views per segment; temporal resolution 20 to 41 ms; and tag spacing 7 mm.
MRI Data Analysis
LV mass, LV end diastolic volume (LVEDV), and ejection fraction (EF) were determined for each study using commercially available software (MASS, version 4.2 Medis). Short axis tagged slices were analyzed by the HARP method (Harmonic Phase, Diagnosoft, Palo Alto, Calif) to assess strain13 as well as strain rate. Strain and strain rate provide complementary information on segmental myocardial function.14 Regional systolic circumferential strains (Ecc) were determined in 4 LV segments (anterior, lateral, inferior, and septal) from the LV midwall layer. Strain rate was derived by strain measurements over time for each LV segment, according to the following formula: equation
|
|
Peak systolic strain was assessed as illustrated in Figure 1. Peak systolic strain rate (SRS) and early filling strain rate (SRE) were derived from strain measures in each segment. By convention, systolic strains and systolic strain rates are negative and increased negativity denotes enhanced function. Early diastolic filling strain rate (SRE) could be assessed in 85% of all studies and represented the main index of diastolic function used.
|
Carotid Imaging
The carotid arteries were evaluated using high resolution B-mode ultrasonography. Each ultrasound study involved the acquisition of 1 real-time transverse (short-axis) scanning sequence and 1 longitudinal image of the common carotid artery. Readers blinded to all clinical information made measurements at a central reading center. The maximal intima-media thickness (IMT) of the common carotid artery was defined as the mean of the maximal IMT of the near and far wall on both the left and right sides, measured at 10 mm proximal to the common carotid bulb. The real-time transverse (short-axis) scanning sequence consisted of a sweep of the carotid artery from the base of the common carotid, up through the bulb, into the internal carotid, and then back down to the base of the common carotid.
Calculation of the Distensibility Coefficient and Young Modulus of Elasticity
For each subject, systolic and diastolic diameters of the common carotid artery were assessed by ultrasonography. Blood pressure measurements were determined by upper arm sphygmomanometry during acquisition of carotid artery measurements. These data were used to assess distensibility (a measure of compliance) and elasticity (a measure of stiffness) of the carotid artery, according to the approach described by Gamble et al15: equation
|
|
|
|
D is the difference between systolic and diastolic diameter; P is the systolic to diastolic pressure change measured at the brachial artery; Ds is the systolic diameter; D is the average carotid artery diameter; and, h is the wall thickness (IMT) of the arterial segment.
Reproducibility of Ultrasound
The ultrasound reproducibility studies were performed in 221 participants, where 211 of the records were intraobserver repeated ultrasound analyses. For distensibility coefficient (DC) and Young’s modulus (YM) of elasticity, the intraobserver intraclass correlation coefficient (ICC) was 0.71 and 0.69, respectively. The interobserver (n=10) ICC was 0.85 and 0.84 for DC and YM, respectively. In rereading exams, the intraobserver variability for DC and YM were also assessed, and in 204 participants the ICC was 0.68 for DC and 0.80 for YM, revealing good to excellent agreement. For carotid IMT measures, the ICC correlation for 31 intraobserver rescan analysis was 0.95. The results for rereads analysis also showed a good correlation, with the intraobserver ICC of 0.98 (n=71) and the interobserver ICC of 0.87 (n=77).
Reproducibility of HARP
To assess the inter- and intraobserver agreement for myocardial MR-tagged image analysis using the HARP technique, 3 independent observers performed 2 separate quantitative strain analyses of myocardial cine MR-tagging images blindly in 24 MESA participants. Interobserver and intraobserver variability for all peak strain values (n=2592) related to tag persistence. Intraclass correlation coefficients R for interobserver and intraobserver agreement for peak systolic midwall ECC were 0.81 and 0.84, respectively, revealing excellent agreement.16
Statistical Analysis
Multiple linear regressions were used to examine the relationship between the distensibility coefficient (DC) and regional systolic (SRS) as well as diastolic function (SRE). We considered the first model to be the simple linear regression of SRS or SRE on DC and YM. The variables adjusted for in the second model were: age, gender, race/ethnicity, body mass index (BMI), systolic and diastolic blood pressure, diabetes, LDL cholesterol, cigarette smoking, and common carotid intima-media thickness (IMT). To determine whether LV hypertrophy (LVH), inflammation, and any therapy for hypertensive disease attenuate the association between subclinical atherosclerosis and regional LV function, we added left ventricular end-diastolic mass, C-reactive protein (CRP), and medications used to control hypertension, in a third model.
Differences in systolic and diastolic strain rates for various DC and YM tertiles across different myocardial regions were compared using one-way ANOVA. Pairwise comparisons were made using a post-hoc Bonferoni correction. Two-sided probability values of less than 0.05 were considered statistically significant. All analyses were performed using SPSS version 13.0.
Results
Demographic, hemodynamic, and risk factors data of the 1100 study participants are presented in Table 1. The mean DC was 0.002±0.001 (mean±SD) and the mean YM was 1378.51±23.53 (mean±SD). The study population was 53.8% male, 28% African American, 29.7% Hispanic, 9.2% Chinese American, and 33.1% Caucasian, with mean age of 66.3±9.7 (mean±SD).
|
Arterial Compliance and Regional Left Ventricular Systolic Function
Figure 2a shows the mean SRS across ranges of DC in all myocardial regions. Individuals in the third (highest) DC tertile had significantly decreased circumferential SRS in the inferior and septal walls compared with individuals in the first (lowest) DC tertile. In other words, increased arterial compliance (represented by higher vascular distensibility) was associated with increased LV systolic function in these regions. Further analyses revealed a direct linear relationship between DC and SRS in all LV wall regions. The results of multiple linear regression analyses adjusting for cardiovascular risk factors and therapies to control hypertension are shown in Table 2, where regression coefficients represent the change in SRS for every 0.1 change in DC. Analyses for Model 1 (unadjusted), Model 2 (adjusted for age, gender, race, BMI, blood pressure, LDL cholesterol, diabetes, smoking, and IMT), and Model 3 (adjusted for LVH, CRP, and antihypertensive medication) demonstrated that decreased arterial compliance was significantly associated with reduced systolic function across all LV segments and slices (P<0.05).
|
|
Table 3 shows the regression results examining the relationship between myocardial systolic strain rate (SRS) and arterial stiffness as assessed by Young’s modulus (YM). We found a consistent association between SRS and YM in the mid-slice, in all LV regions in the unadjusted model, and even after adjustment for variables in model 2. After we include CRP, LV mass, and use of antihypertensive medication (model 3), SRS from the anterior and lateral regions remained significantly associated with YM, whereas SRS from the inferior and septal regions were no longer associated. When evaluating the other slices, SRS from the apical slice in anterior and lateral regions had significant associations with YM (P<0.05) in all 3 statistical models. In contrast, SRS from the basal slice was not significantly associated with YM in any region, even in unadjusted models. The distribution of mean systolic strain rates (SRS) across ranges of Young modulus of elasticity in each ventricular wall region is demonstrated in Figure 2b, where there is no difference among tertiles in the different LV myocardial regions.
|
Arterial Compliance and Regional Left Ventricular Diastolic Function
Figure 3 illustrates the distribution of mean SRE values across ranges of DC in all myocardial regions. Peak early diastolic strain rates were significantly higher among individuals in the third (highest) DC tertile compared with those in the first (lowest) DC tertile in the lateral (1.75 s–1 versus 1.98 s–1, P<0.05) and septal (1.25 s–1 versus 1.45 s–1, P<0.05) wall regions. Because SRE values are normally positive, higher values (correlated here with increased arterial compliance) represent increased diastolic function in these myocardial regions. Multiple linear regression analyses also demonstrated a relationship between increased carotid distensibility and enhanced LV diastolic function (please see supplemental Table I, available online at http://atvb.ahajournals.org), where regression coefficients (RC) represent the change in SRE for every 0.1 change in DC. We detected positive correlations between arterial compliance and diastolic regional myocardial function throughout segments of the mid and apical LV wall regions. Furthermore, associations between increased carotid DC and greater diastolic function remained even after adjustment for risk factors and therapies to control blood pressure, with significant results in the septal and anteroapical regions (P<0.01). With respect to specific wall regions, our analyses also showed that greater SRE was associated with a higher DC in the anterior wall (RC for SRE=7.8) and septum (RC for SRE=7.9; P<0.05) in the apical slice. Diastolic function was also directly related to compliance in the lateral and inferior regions (mid slice) in the unadjusted model, and in the septal region (midslice) even in the fully adjusted model (RC for SRE= 7.8, please see supplemental Table I). We found strong inverse associations of early diastole SRE and YM (the higher the YM, less diastolic function only in the anterior LV region from mid and apical slices, that remained significant even in fully adjusted models (P<0.05).
|
Pulse Pressure and Regional Myocardial Function
Linear regression analyses were performed between regional myocardial function and pulse pressure (systolic blood pressure minus diastolic blood pressure). We did not find any significant association between pulse pressure and systolic strain rate or diastolic strain rate for the left ventricular basal, mid and apical slices.
Discussion
This study demonstrates a consistent association between carotid arterial stiffness and impaired regional LV function in a cohort of asymptomatic individuals without previously diagnosed cardiovascular disease. By highlighting the presence of early vascular dysfunction in the setting of subclinical ventricular dysfunction, this study provides evidence in support of a novel paradigm for understanding the pathogenesis of HF. It is the first to relate measures of arterial stiffness to myocardial regional function in a large multiethnic population. The uniqueness of the study is also underscored by the complex methodology used to quantify both vascular material properties and myocardial deformation measured in detail by MRI tagging.
Elevated peripheral arterial resistance is commonly found in the setting of overt, and often advanced, HF and has been considered an adaptive response to impaired ventricular contractility and subsequent low-perfusion states.17 Investigations over the last decade have sought to confirm the presence of arterial stiffening during the early and not just the late phases of myocardial dysfunction to clarify its potential role in the development of HF.18 However, studies of the association between HF and more direct measures of vascular stiffness have been less consistent,19 possibly because of the effects of survival bias, blood pressure parameters, or functional vascular changes associated with advanced HF. Using the distensibility coefficient, a direct measure of carotid arterial compliance, ours is the first population-based study to confirm the presence of arterial stiffness in the setting of subclinical myocardial dysfunction.
Decreased arterial compliance is one of the earliest detectable manifestations of adverse structural and functional changes in the vessel wall. Stiffening in both medium-sized and large elastic arteries is associated with multiple cardiovascular risk factors—including hypertension, dyslipidemia, obesity, smoking, diabetes, and aging—all of which also favor the development of atherosclerosis in previous studies20 as well as in MESA.21 Not surprisingly, previous studies have identified arterial stiffness itself as a risk factor for myocardial infarction22,23 as well as clinical HF.24 It seems logical then that impaired arterial compliance would be associated with ventricular dysfunction via atherosclerosis and related ischemic events. However, we found arterial stiffness related to subclinical myocardial dysfunction even after controlling for multiple risk factors and in the absence of clinical cardiovascular disease.
Previous studies have also described an association between elevated pulse pressure and incident HF in the absence of or independent from any coexistent CAD.18 Together, these findings are consistent with evidence demonstrating that although asymptomatic LV dysfunction confers a high risk of progression to clinical HF, the majority of cases are not precipitated by identifiable ischemic events.25 However, the possible role of subclinical atherosclerosis cannot be discounted. Arterial stiffness is correlated with the presence and severity of atherosclerosis,26 and we have previously shown that subclinical atherosclerosis is also associated with regional myocardial dysfunction.27,28 Conduit vessel resistance, particularly in the setting of coronary stenoses, may increase myocardial vulnerability to falls in coronary perfusion pressure and subendocardial ischemia.29,30 Furthermore, our data demonstrate that the association between arterial stiffening and myocardial dysfunction can be regional in nature, and heterogeneously located plaques may influence the regionality of ventricular dysfunction seen in this study. Notwithstanding the possible role of subclinical atherosclerosis, there are several mechanisms that also may contribute to the relationship between arterial stiffening and myocardial dysfunction. Any decrease in diastolic blood pressure, as a result of arterial stiffness, may compromise coronary artery blood flow, even in the absence of stenoses.23 Impaired myocardial oxygen supply, particularly at the level of small coronary resistance vessels, may lead to fibrosis and the deposition of myocardial and perivascular collagen.31 Reduced arterial compliance also may be a mechanism by which overactivity of the renin-angiotensin-aldosterone system produces both vascular and ventricular damage and adverse remodeling.32
Undoubtedly the most studied comorbid condition associated with both arterial stiffening and HF is hypertension. A compelling and plausible explanation for the relationship between arterial compliance and LV dysfunction invokes longstanding high blood pressure, chronic pulsatile hemodynamic loading on the LV, and subsequent ventricular hypertrophy predisposing to impaired function. Interestingly, however, we found that carotid arterial compliance was associated with regional myocardial function even after adjustment for blood pressure, therapies to control hypertension, and LV mass. Therefore, it appears from our results that arterial stiffness itself, and not just its sequelae, are directly associated with alterations in regional myocardial function. This finding coincides with recent work demonstrating that concurrent vascular and ventricular stiffening can progress even in the absence of cardiac hypertrophy.33
This study includes 1100 subjects, making it the first and largest community-based study of the association between arterial stiffening, assessed using the distensibility coefficient, and early ventricular dysfunction, represented by circumferential strain measurements from cardiovascular MRI tissue tagging. Cardiovascular MRI is uniquely accurate and reproducible in its application of tissue tagging for objective assessments of regional myocardial dysfunction. However, some technical limitations are inherent to this imaging modality. Because tags can sometimes fade before the appearance of the associated QRS on the rhythm strip, strain profiles and curves do not always return to baseline (zero) at end-diastole.16 Several additional factors, including the normal beat-to-beat variation in stroke volume, may affect the precision of MRI tagging. Since strain rate is a derivative strain over time, and directly dependent on strain profile, 15% of strain rate curves could not be assessed reliably. In this regard, echocardiography may offer superior temporal resolution in assessing strain rate.
Our results demonstrate subclinical alterations in myocardial contractility in the absence of overt heart failure. However, the prognostic significance of such asymptomatic regional myocardial dysfunction in individuals with decreased arterial compliance, as seen in this study, has yet to be determined. Because of pulse pressure amplification between central and peripheral arteries (amplification phenomenon) it is generally considered less accurate to use brachial pulse pressure as a surrogate for aortic or carotid pulse pressure.34 In younger subjects, the "stiffness gradient" along the arterial tree can generate wave reflections and increase the pressure amplification directly, because the central arteries are usually more elastic than peripheral arteries. However, this gradient can be reversed with aging or hypertension.35,36 In our study, the distensibility indices were based on brachial rather than carotid pulse pressures, but we have reason to believe that this would not differentially affect our regional myocardial function associations, because the population included participants aged 45 to 84. In contrast to systemic arterial stiffness, which can only be estimated from models of the circulation, the regional and local methods can be measured directly, noninvasively, at various sites along the arterial tree.37–39 More importantly, the cross sectional nature of this study precludes inferring causality between arterial stiffening and regional myocardial alterations, although this may be the subject of future longitudinal studies. Indeed, we were not able to explore the relationship with any drug intervention given the strict observational nature of the MESA study. Because MESA includes participants from 4 different ethnic groups, our study sample was more diverse than populations previously studied.18 However, the generalizability of our results may still be limited by sampling bias inherent to volunteer selection for a study such as MESA.
Conclusions
The presence of decreased arterial compliance in the setting of asymptomatic regional myocardial dysfunction suggests that arterial stiffness may be involved in the pathogenesis of HF. Multiple plausible explanations for this relationship exist, and thus further research is needed to elucidate the role of vascular compliance in the development of ventricular dysfunction and failure.
Acknowledgments
The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org USA.
Sources of Funding
This study was supported by the NHLBI grant (RO1-HL66075-01) and the MESA study contracts (NO1-HC-9808, NO1-HC-95168 and NO1-HC-95169). Dr Lima is also supported by the Reynolds Foundation, and Dr Fernandes was a recipient of a research grant from CAPES, Ministry of Education, Brazilian Government.
Disclosures
None.
Footnotes
Original received July 13, 2007; final version accepted October 15, 2007.
References
1. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction N Engl J Med. 2006.
2. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure–abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med. 2004; 350: 1953–1959.
3. Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002; 288: 2144–2150.
4. Kass DA. Ventricular arterial stiffening: integrating the pathophysiology. Hypertension. 2005; 46: 185–193.
5. Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations. Circulation. 2003; 107: 714–720.
6. Pini R, Cavallini MC, Bencini F, Silvestrini G, Tonon E, De Alfieri W, Marchionni N, Di Bari M, Devereux RB, Masotti G, Roman MJ. Cardiovascular remodeling is greater in isolated systolic hypertension than in diastolic hypertension in older adults: the Insufficienza Cardiaca negli Anziani Residenti (ICARE) a Dicomano Study. J Am Coll Cardiol. 2002; 40: 1283–1289.
7. Roman MJ, Ganau A, Saba PS, Pini R, Pickering TG, Devereux RB. Impact of arterial stiffening on left ventricular structure. Hypertension. 2000; 36: 489–494.
8. Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA. Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation. 2005; 112: 2254–2262.
9. Saba PS, Ganau A, Devereux RB, Pini R, Pickering TG, Roman MJ. Impact of arterial elastance as a measure of vascular load on left ventricular geometry in hypertension. J Hypertens. 1999; 17: 1007–1015.[CrossRef][Medline] [Order article via Infotrieve]
10. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, Jacobs Jr. DR, Kronmal R, Liu K, Nelson JC, O’Leary D, Saad MF, Shea S, Szklo M, Tracy RP. Multi-Ethnic Study of Atherosclerosis: Objectives and Design. Am J Epidemiol. 2002; 156: 871–881.
11. Rosen BD, Saad MF, Shea S, Nasir K, Edvardsen T, Burke G, Jerosch-Herold M, Arnett DK, Lai S, Bluemke DA, Lima JAC. Hypertension and Smoking Are Associated With Reduced Regional Left Ventricular Function in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol. 2006; 47: 1150–1158.
12. Axel L, Dougherty L. Heart wall motion: improved method of spatial modulation of magnetization for MR imaging. Radiology. 1989; 172: 349–350.
13. Osman NF, Prince JL. Visualizing myocardial function using HARP MRI. Phys Med Biol. 2000; 45: 1665–1682.[CrossRef][Medline] [Order article via Infotrieve]
14. Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation. 2000; 102: 1158–1164.
15. Gamble G, Zorn J, Sanders G, MacMahon S, Sharpe N. Estimation of arterial stiffness, compliance, and distensibility from M-mode ultrasound measurements of the common carotid artery. Stroke. 1994; 25: 11–16.[Abstract]
16. Castillo E, Osman NF, Rosen BD, El-Shehaby I, Pan L, Jerosch-Herold M, Lai S, Bluemke DA, Lima JA. Quantitative assessment of regional myocardial function with MR-tagging in a multi-center study: interobserver and intraobserver agreement of fast strain analysis with Harmonic Phase (HARP) MRI. J Cardiovasc Magn Reson. 2005; 7: 783–791.[CrossRef][Medline] [Order article via Infotrieve]
17. Gaasch WH, Zile MR. Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med. 2004; 55: 373–394.[CrossRef][Medline] [Order article via Infotrieve]
18. Haider AW, Larson MG, Franklin SS, Levy D. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med. 2003; 138: 10–16.
19. Sutton-Tyrrell K, Najjar SS, Boudreau RM, Venkitachalam L, Kupelian V, Simonsick EM, Havlik R, Lakatta EG, Spurgeon H, Kritchevsky S, Pahor M, Bauer D, Newman A. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation. 2005; 111: 3384–3390.
20. Mancia G, Giannattasio C, Grassi G. Arterial distensibility in cardiovascular diseases. J Nephrol. 1998; 11: 284–288.[Medline] [Order article via Infotrieve]
21. Sharrett AR, Ding J, Criqui MH, Saad MF, Liu K, Polak JF, Folsom AR, Tsai MY, Burke GL, Szklo M. Smoking, diabetes, and blood cholesterol differ in their associations with subclinical atherosclerosis: the Multiethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2006; 186: 441–447.[CrossRef][Medline] [Order article via Infotrieve]
22. Domanski MJ, Mitchell GF, Norman JE, Exner DV, Pitt B, Pfeffer MA. Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction. J Am Coll Cardiol. 1999; 33: 951–958.
23. Benetos A, Rudnichi A, Safar M, Guize L. Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension. 1998; 32: 560–564.
24. Vaccarino V, Holford TR, Krumholz HM. Pulse pressure and risk for myocardial infarction and heart failure in the elderly. J Am Coll Cardiol. 2000; 36: 130–138.
25. Wang TJ, Evans JC, Benjamin EJ, Levy D, LeRoy EC, Vasan RS. Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation. 2003; 108: 977–982.
26. Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis. Circulation. 1989; 80: 78–86.
27. Edvardsen T, Detrano R, Rosen BD, Carr JJ, Liu K, Lai S, Shea S, Pan L, Bluemke DA, Lima JA. Coronary artery atherosclerosis is related to reduced regional left ventricular function in individuals without history of clinical cardiovascular disease: the Multiethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2006; 26: 206–211.
28. Fernandes VR, Polak JF, Edvardsen T, Carvalho B, Gomes A, Bluemke DA, Nasir K, O’Leary DH, Lima JA. Subclinical atherosclerosis and incipient regional myocardial dysfunction in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol. 2006; 47: 2420–2428.
29. Watanabe H, Ohtsuka S, Kakihana M, Sugishita Y. Coronary circulation in dogs with an experimental decrease in aortic compliance J Am Coll Cardiol. 1993; 21: 1497–1506.[Abstract]
30. Kass DA, Saeki A, Tunin RS, Recchia FA. Adverse influence of systemic vascular stiffening on cardiac dysfunction and adaptation to acute coronary occlusion Circulation. 1996; 93: 1533–1541.
31. Strauer BE. Development of cardiac failure by coronary small vessel disease in hypertensive heart disease? J Hypertens Suppl. 1991; 9: S11–S20.[Medline] [Order article via Infotrieve]
32. Mahmud A, Feely J. Arterial stiffness and the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst. 2004; 5: 102–108.
33. Kass DA. Age-related changes in venticular-arterial coupling: pathophysiologic implications. Heart Fail Rev. 2002; 7: 51–62.[CrossRef][Medline] [Order article via Infotrieve]
34. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006; 27: 2588–2605.
35. Boutouyrie P, Laurent S, Benetos A, Girerd XJ, Hoeks AP, Safar ME. Opposing effects of ageing on distal and proximal large arteries in hypertensives. J Hypertens Suppl. 1992; 10: S87–S91.[CrossRef][Medline] [Order article via Infotrieve]
36. Benetos A, Laurent S, Hoeks AP, Boutouyrie PH, Safar ME, Boutouyrie P, Girerd XJ. Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries Opposing effects of ageing on distal and proximal large arteries in hypertensives. Arterioscler Thromb. 1993; 13: 90–97.
37. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE. Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens. 2002; 15: 426–444.[CrossRef][Medline] [Order article via Infotrieve]
38. Pannier BM, Avolio AP, Hoeks A, Mancia G, Takazawa K. Methods and devices for measuring arterial compliance in humans. Am J Hypertens. 2002; 15: 743–753.[CrossRef][Medline] [Order article via Infotrieve]
39. Van Bortel LM, Duprez D, Starmans-Kool MJ, Safar ME, Giannattasio C, Cockcroft J, Kaiser DR, Thuillez C, Laurent S, Van Bortel L, Boutouyrie P, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H. Clinical applications of arterial stiffness, Task Force III: recommendations for user procedures Expert consensus document on arterial stiffness: methodological issues and clinical applications. Am J Hypertens. 2002; 15: 445–452.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  S. Cheng, V. R.S. Fernandes, D. A. Bluemke, R. L. McClelland, R. A. Kronmal, and J. A.C. Lima Age-Related Left Ventricular Remodeling and Associated Risk for Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis Circ Cardiovasc Imaging, May 1, 2009; 2(3): 191 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Brinkley, B. J. Nicklas, A. M. Kanaya, S. Satterfield, E. G. Lakatta, E. M. Simonsick, K. Sutton-Tyrrell, S. B. Kritchevsky, and for the Health, Aging, and Body Composition Study Plasma Oxidized Low-Density Lipoprotein Levels and Arterial Stiffness in Older Adults: The Health, Aging, and Body Composition Study Hypertension, May 1, 2009; 53(5): 846 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Antonini-Canterin, S. Carerj, V. Di Bello, G. Di Salvo, S. La Carrubba, O. Vriz, D. Pavan, A. Balbarini, G. L. Nicolosi, and On behalf of the Research Group of the Italian Soc Arterial stiffness and ventricular stiffness: a couple of diseases or a coupling disease? A review from the cardiologist's point of view Eur J Echocardiogr, January 1, 2009; 10(1): 36 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Bluemke, R. A. Kronmal, J. A.C. Lima, K. Liu, J. Olson, G. L. Burke, and A. R. Folsom The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J. Am. Coll. Cardiol., December 16, 2008; 52(25): 2148 - 2155. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||