Author + information
- Received April 8, 2014
- Revision received August 17, 2014
- Accepted September 8, 2014
- Published online December 23, 2014.
- Alban Redheuil, MD, PhD∗,†∗ (, )
- Colin O. Wu, PhD‡,
- Nadjia Kachenoura, PhD∗,
- Yoshiaki Ohyama, MD§,
- Raymond T. Yan, MD‖,
- Alain G. Bertoni, MD, MPH¶,
- Gregory W. Hundley, MD¶,
- Daniel A. Duprez, MD, PhD#,
- David R. Jacobs Jr., PhD#,
- Lori B. Daniels, MD, MAS∗∗,
- Christine Darwin, MD††,
- Christopher Sibley, MD‡‡,
- David A. Bluemke, MD, PhD‡‡ and
- João A.C. Lima, MD§
- ∗Sorbonne Universités, Université Pierre et Marie Curie UPMC, Laboratoire d’imagerie biomédicale INSERM UMR_S1146, Paris, France
- †Cardiovascular Imaging Department and ICAN Imaging Core Lab, La Pitié Salpêtrière, Paris, France
- ‡Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland
- §Division of Cardiology and Radiology, Johns Hopkins University, Baltimore, Maryland
- ‖Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- ¶Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
- #Division of Cardiology and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
- ∗∗Division of Cardiology, University of California San Diego, La Jolla, California
- ††University of California Los Angeles Research Center, Alhambra, California
- ‡‡Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland
- ↵∗Reprint requests and correspondence:
Dr. Alban Redheuil, Cardiovascular Imaging Department DICVRI, Cardiology Institute, La Pitié Salpêtrière (APHP) and Sorbonne Universités, Université Pierre et Marie Curie UPMC, INSERM UMR S1146, Laboratoire d’imagerie biomédicale, ICAN Imaging Core Lab, 91, boulevard de l’hôpital, 75013 Paris, France.
Background The predictive value of ascending aortic distensibility (AAD) for mortality and hard cardiovascular disease (CVD) events has not been fully established.
Objectives This study sought to assess the utility of AAD to predict mortality and incident CVD events beyond conventional risk factors in MESA (Multi-Ethnic Study of Atherosclerosis).
Methods AAD was measured with magnetic resonance imaging at baseline in 3,675 MESA participants free of overt CVD. Cox proportional hazards regression was used to evaluate risk of death, heart failure (HF), and incident CVD in relation to AAD, CVD risk factors, indexes of subclinical atherosclerosis, and Framingham risk score.
Results There were 246 deaths, 171 hard CVD events (myocardial infarction, resuscitated cardiac arrest, stroke and CV death), and 88 HF events over a median 8.5-year follow-up. Decreased AAD was associated with increased all-cause mortality with a hazard ratio (HR) for the first versus fifth quintile of AAD of 2.7 (p = 0.008) independent of age, sex, ethnicity, other CVD risk factors, and indexes of subclinical atherosclerosis. Overall, patients with the lowest AAD had an independent 2-fold higher risk of hard CVD events. Decreased AAD was associated with CV events in low to intermediate- CVD risk individuals with an HR for the first quintile of AAD of 5.3 (p = 0.03) as well as with incident HF but not after full adjustment.
Conclusions Decreased proximal aorta distensibility significantly predicted all-cause mortality and hard CV events among individuals without overt CVD. AAD may help refine risk stratification, especially among asymptomatic, low- to intermediate-risk individuals.
Conventional risk factors associated with atherosclerosis are major determinants of cardiovascular disease (CVD). Recently, a complement to this classic view was proposed and termed the vascular aging continuum, starting from age-related arterial stiffening leading to cardiac disease, heart failure (HF), and microvascular disease of the brain and kidneys, with resulting disability and eventually death (1).
The direct measurement of aortic stiffness as a marker of early arterial damage may be important. Although the usual onset of CVD appears in middle and older age, a large body of evidence suggests that subclinical vascular and cardiac alterations start much earlier in life (2–6). Global arterial stiffness measured as carotid-femoral pulse wave velocity (PWV) may independently predict incident CV events among patients as well as in the general population separate from traditional CVD risk factors (7). Subsequently, reference values and determinants of PWV in healthy individuals, with and without CVD risk factors, have been described for large populations (8) and recently included in the guidelines (9). In healthy humans, reduced ascending aortic distensibility (AAD) as illustrated in Figure 1, has been shown to be an early marker of subclinical vascular alteration. However, little is known of the prognostic value of altered proximal aortic function, which is responsible for most of the mechanical buffering and cushioning in the circulatory system, thus influencing ventricular-vascular coupling (10). Recently, Maroules et al. (11) reported modest associations of aortic distensibility with a composite of soft and hard CV endpoints in the Dallas Heart Study, whereas thoracic aorta compliance, measured by transesophageal echocardiography, may be comparable to carotid-femoral PWV for predicting mortality (12).
We postulated that a direct measure of aortic function—AAD—using cardiac magnetic resonance (CMR) imaging (13), may be directly related to hard CV events and mortality, independent of classic CVD risk factors. Thus, the aim of our study was to determine the prognostic value of AAD beyond established indexes of subclinical atherosclerosis and conventional risk factors included in the global Framingham risk score. To this end, we measured aortic distensibility and ascertained the post-scan occurrence of hard CVD events in participants within the MESA (Multi-Ethnic Study of Atherosclerosis) cohort.
MESA (14) is a population-based sample of 6,814 men and women aged 45 to 84 years without clinical CVD at the time of enrollment who identified themselves as white, African American, Hispanic, or Chinese from 6 U.S. communities (Baltimore, New York, Minneapolis, Winston-Salem, Los Angeles, and Chicago). Out of 5,098 participants who took part in the CV CMR imaging examination, 3,675 subjects underwent suitable AAD measurements for analysis. The study was approved by the institutional review boards at all recruiting field centers, and all participants provided written informed consent.
Aortic and CMR imaging
CMR imaging was performed using 1.5-T whole-body magnetic resonance imaging scanners as previously described (15). In summary, gradient echo phase-contrast cine CMR imaging with electrocardiographic gating was performed to evaluate aortic distensibility. Images of the ascending and descending aorta were obtained in the transverse plane perpendicular to the aortic lumen at the level of the right pulmonary artery. Imaging parameters included repetition time of 10 ms, echo time of 1.9 ms, field of view of 34 cm, slice thickness of 8 mm, matrix of 256 × 224, temporal resolution of 20 ms, encoding velocity of 150 cm/s, and bandwidth of 32 kHz.
As illustrated in Figure 2, cross-sectional lumen areas of the ascending aorta were determined using a semi-automated contouring method with previously reported interreader reproducibility (16). The maximal (Amax) and minimal (Amin) aortic areas and change in aortic area defined as ΔA = (Amax − Amin) were used to calculate the AAD in each subject as follows, with PP being pulse pressure (in mm Hg): AAD = ΔA/(Amin × PP) in 10−3 mm Hg−1.
CMR imaging was performed with measurements of left ventricular (LV) mass as previously described (17).
CVD risk factors and measures of subclinical atherosclerosis
During baseline examination, all participants completed standardized questionnaires to obtain information about smoking history, pack-years of smoking, medication usage, diagnosis of high cholesterol, and diabetes. Height and weight were measured, and resting systolic (SBP) and diastolic (DBP) blood pressures were measured 3 times with an automated oscillometric sphygmomanometer with participants in the seated position. The average of the last 2 measurements was used in analysis. Mean brachial blood pressure (MBP) was calculated as: (2 × DBP + SBP)/3. The ankle-brachial pressure index (ABI) was calculated by dividing SBP at the ankle by brachial SBP, as previously reported (18). Heart rate was monitored and recorded at the time of the CMR examination. Total and high-density lipoprotein (HDL) cholesterol and glucose levels were measured from blood samples obtained after a 12-h fast. Diabetes mellitus was defined as fasting glucose ≥126 mg/dl or use of insulin or oral hypoglycemic medication. Among those without diabetes, impaired fasting glucose was defined as fasting glucose from 100 to 125 mg/dl. Hypertension was defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg, or current use of antihypertensive medications. Carotid artery intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, was reported to further characterize subclinical atherosclerosis. A composite Z-score for overall maximal IMT was calculated by summing the 2 carotid IMT sites after normalization by the SD of each measure and divided by the SD of the sum (19). IMT of the right and left near and far walls of the common and internal carotid artery were measured by B-mode echography. Mean coronary artery calcium (CAC) score was measured by computed tomography as previously described (19).
The sex-specific global CVD Framingham 10-year risk score was calculated as described by D’Agostino et al. (20), on the basis of these risk factors at baseline: age, total cholesterol level, HDL cholesterol level, SBP, antihypertensive treatment, smoking, and diabetes.
Follow-up for CVD events and deaths
Participants were followed for death and incident CVD events for an average 8.5 years from baseline examination. In addition to 4 follow-up MESA study examinations, a telephone interviewer contacted each participant every 9 to 12 months to inquire about all interim hospital admissions, CVD outpatient diagnoses, and deaths. Medical records were available for an estimated 99% of hospitalized CVD events and information was available on 97% of outpatient CVD diagnostic encounters. Events and incidence dates were adjudicated by 2 blinded physicians from the MESA study events committee using pre-specified criteria. Adjudication of events has been previously detailed (17). Hard CVD events in the MESA trial were required to be symptomatic and included myocardial infarction, resuscitated cardiac arrest, stroke, and CV death. Incident HF events were recorded. All deaths were identified. For potential CVD deaths, cause was assigned through committee review. For other deaths, the underlying cause was obtained through state or city vital statistics departments.
Participant characteristics were reported according to outcome as percentages for categorical variables and means and SD for continuous variables. Baseline characteristics were compared separately between both outcome groups (death and incident CVD) and the group without events using a Student t test for continuous variables and a chi-square test for categorical variables.
The relationships between AAD and time-to-death/time-to-CVD events and HF events were studied using univariate and multivariate Cox regression models. For the definition of time to death, subjects who were alive before loss to follow-up were treated as right censored. For the definition of time-to-CVD or HF events, subjects who did not have events (including CVD death) before loss to follow-up were treated as right censored. Univariate Cox proportional hazards regression models were first fitted for each time to event (time to death, time to CVD, time to HF) variable for quintiles of AAD without adjustment of other covariates because the effects of AAD on the hazard functions were nonlinear. Table 1 presents distribution of AAD values in quintiles. Subsequently, we studied the predictive value of AAD by quintiles for mortality, hard CVD events, and HF events compared with: 1) constitutional factors; 2) CV risk factors; 3) measures of subclinical atherosclerosis individually and together (ABI, carotid IMT, CAC); and 4) left ventricular hypertrophy (LVH). ABI was considered abnormal when <1.0 or ≥1.4 as previously determined to be related to outcome in the MESA trial (18). LVH was defined as LV mass ≥90th percentile in the study population (197 g). We considered a 10-year CVD risk to be low or intermediate when <10%, corresponding to our cohort’s median risk, and high when ≥10%.
Constitutional variables of adjustment for multivariate Cox regression models included age category, sex, weight, height, and ethnicity. CV risk factors used for further adjustment of the models included MBP, antihypertensive medication (yes/no), diabetes (yes/no), total and HDL cholesterol levels, and cigarette smoking in pack-years. Kaplan-Meier estimates of the cumulative event-free distribution functions were calculated for time to mortality and time to CVD according to extreme quintiles of AAD. Values of p < 0.05 were considered statistically significant. Confidence intervals (CIs) were expressed as 95% CIs. All analyses were performed using Stata 12C (StataCorp, College Station, Texas).
Participant characteristics and CVD risk profile according to outcome
Our analysis included the 3,675 MESA participants who had aortic distensibility measured by CMR imaging. There were 246 deaths, 171 hard CV events, and 88 incident HF events over a median 8.5 years of follow-up. The participants’ mean age at baseline was 60 ± 10 years (range: 44 to 84 years). Of the participants, 54% were female, 11% Chinese American, 29% African American, 17% Hispanic, and 43% white. Table 2 shows baseline characteristics of participants according to events. MESA participants with aortic data more often tended to be white or African American and female and overall have a moderately lower risk profile and subclinical atherosclerosis burden (IMT, ABI, CAC) than participants without aortic CMR imaging. Although statistically significant in large population samples, these differences do not seem to be within clinically relevant ranges.
Overall, the most frequent hard CV events were myocardial infarction (n = 85), stroke (n = 63), and CV death (n = 52) (multiple events possible). There was, proportionally to the group without incident CVD or death, an increased proportion of white individuals among those who developed CVD and a higher proportion of African Americans among those who died. Subjects who died were older, more often male, hypertensive, active smokers, and diabetic or with impaired fasting glucose; body size, body mass index, and heart rate were not different between the 2 groups. Subjects who died had slightly higher total cholesterol levels but similar HDL cholesterol levels and increased SBP and PP but similar DBP as subjects without events. Subjects with incident CVD were older, more often male, hypertensive, active smokers, and diabetic, plus more likely to have increased weight (+10 kg on average) and body mass index (+1 point) than subjects without events. Although total cholesterol levels were not increased in the CVD group, HDL cholesterol levels were significantly lower and all components of blood pressure (SBP, DBP, and PP) were increased compared with the group without events; heart rate was slightly higher. AAD and ABI were lower, and carotid IMT, CAC, and LV mass were significantly higher in both event groups compared with participants without events (Table 2).
Relationship of AAD to mortality
The absolute rate of death was 9.3% and incidence rate 0.04 per 1,000 person-years in participants with the lowest levels of aortic distensibility (Q1) compared with 1.5% and 0.003 per 1,000 person-years in participants with the greatest aortic distensibility (Q5) (p < 0.001). The Kaplan-Meier analysis (Central Illustration, upper panel) showed a significant decrease in survival in the Q1 group compared with the group with the most preserved aortic distensibility (p < 0.001). The difference in survival between Q1 and Q5 of AAD was marked and consistently significant over time. The hazard ratio (HR) for death among Q1 participants was significantly increased at 6.5 compared with that of the Q5 participants in univariate analysis (p < 0.001), 2.7 after adjustment for age, sex, ethnicity, and body size and 2.7 after further adjustment for smoking, antihypertensive medication, diabetes, and MBP (all p < 0.01) (Table 3). This result was not substantially changed after adjustment for brachial SBP or PP instead of mean pressure. Furthermore, this result remained consistent in the fully adjusted model after further individual or grouped adjustment for ABI, presence of CAC, carotid IMT, and presence of LVH (all p ≤ 0.01) (Table 3).
Relationship of AAD to CVD events
The absolute and incident rates of hard CVD were respectively 6.7% and 0.03 per 1,000 person-years in Q1 participants compared with 1.4% and 0.005 per 1,000 person-years in Q5 participants (p < 0.001). The Kaplan-Meier analysis showed a significant decrease in CVD-free survival in the Q1 group compared with subjects with preserved aortic distensibility (Central Illustration, lower panel). The difference in incident CVD between Q1 and Q5 of AAD was constant, notable, and significant over time. However, some degree of nonlinearity in HR distribution was present across intermediate quintiles of AAD. The HR for CVD in relationship to the degree of aortic stiffness is summarized in Table 4.
Q1 participants had an unadjusted HR for incident CVD of 5.7 (p < 0.001), 3.3 (p = 0.002) after adjustment for age, body size, and ethnicity, and 2.2 in the fully adjusted model on CV risk factors including MBP. A similar result was found after adjustment for brachial SBP or PP instead of MBP.
Overall, increased aortic stiffness predicted CVD in the unadjusted and minimally adjusted models independently of the individual effect of ABI, carotid IMT, presence of CAC, or LVH (Table 4). In the fully adjusted models, AAD remained predictive of CVD after further adjustment for carotid IMT, which itself was not a significant predictor. However, AAD did not reach significance as a predictor of CVD when ABI and CAC were added individually or together to the fully adjusted models. Neither AAD nor LVH was a significant predictor in the fully adjusted models when entered together.
When stratified according to Framingham risk category (Table 5), AAD significantly predicted CVD in low- to intermediate-risk individuals (10-year CVD risk <10%), with an HR of 8.9 (p = 0.001) in univariate analysis and 5.3 (p = 0.03) in the fully adjusted model, but did not reach significance in high-risk individuals (10-year CVD risk ≥10%). Additionally, reduced aortic distensibility remained a significant predictor of incident CVD in the adjusted model in low- to intermediate-risk individuals even after further individual or grouped adjustment for ABI, CAC, and carotid IMT and after individual adjustment for LVH. Notably, ABI remained a significant predictor of CVD in low- to intermediate-risk individuals, whereas CAC, carotid IMT, and LVH did not (Table 5).
Incident HF was associated with altered AAD (Q1) in the univariate model, with an HR of 6.0 (95% CI: 2.1 to 17.4; p = 0.001), but this relationship failed to reach significance in the intermediate and fully adjusted models (HR: 2.1; p = 0.18 and HR: 1.4; p = 0.56, respectively).
We studied proximal aortic distensibility in a large sample from the MESA study. Altered distensibility of the ascending aorta was associated with increased risk of: 1) all-cause mortality independent of age and traditional CVD risk factors; and 2) incident CVD independent of age and traditional CVD risk factors in otherwise low- to moderate-risk participants. After adjustment for traditional CV risk factors, individuals with markedly altered AAD for their age group had a 2-fold increase in risk of all-cause death in comparison with individuals with preserved aortic distensibility. Additionally, individuals with high aortic stiffness had an almost 4-fold increase in risk of incident CVD compared with individuals with preserved aortic elasticity if they had a low- to intermediate-risk CVD profile at baseline. However, high aortic stiffness only marginally predicted higher levels of CVD in individuals with a high baseline CVD risk profile. This is the first report to demonstrate independent association of aortic distensibility with mortality and hard CVD events.
Important target organs, such as the heart and brain, are directly linked both anatomically and physiologically to the central elastic arterial sector composed of the ascending aorta, aortic arch, and carotid arteries. In this regard, the predictive value of carotid-femoral PWV, a global estimate of arterial stiffness, has been established in the general population and in patients with CVD (7,10,21–23). The importance of the proximal aorta in the buffering function of systolic load and therefore in preserving vascular-ventricular coupling is paramount (24–27). Age is a main determinant of arterial structural and functional changes, and subclinical alteration of proximal aortic function can occur early. However, the complex interplay between structural and functional changes in both the aorta and left ventricle through vascular-ventricular coupling is mainly driven by the aging process and further aggravated by atherosclerosis, the prevalence of which also increases with age. The proximal aorta dilates and elongates during normal aging secondary to structural wall changes that include thinning and fragmentation of elastin fibers within the media. This process ultimately leads to arterial stiffness and increased afterload on the left ventricle, with consequent LVH and systolic and diastolic dysfunction (26,27). Hundley et al. (28) showed the relationship between aortic stiffness and impaired exercise capacity in the elderly and Fernandes et al. (4) showed the relationship between increased carotid stiffness and subclinical alteration in LV systolic and diastolic myocardial deformation in the MESA study.
Aortic dilation and elongation associated with aortic stiffening (29) lead to a static aortic volume increase partly compensating for the loss of proximal aortic elasticity (systolic cushioning function and diastolic recoil) (Figure 1). Until advanced age, or earlier as a result of lifelong aggravating factors such as hypertension, diabetes, or CVD, both aortic and LV function decline proportionally such that the vascular-ventricular coupling is preserved. However, when aortic stiffness is very high, aortic and cardiac complications may occur secondary to a sharp increase in arterial load. This may explain in part why this study and others have found extreme aorta stiffness values to be the most relevant in predicting adverse outcomes. However, a specific cutpoint has not been defined.
Additionally, flow alterations secondary to large-artery structural and functional modifications are transmitted to smaller arteries and may lead to cardiac, cerebral, and renal microvascular damage and subsequent target organ failure. The resulting global vascular aging continuum may account for the strong association between altered AAD and all-cause mortality beyond CVD’s specific role.
Our results are consistent with those of prior studies on global measures of aortic stiffness, such as the Framingham community-based data of Mitchell et al. (21), regarding superiority of a direct measure of aortic stiffness over conventional brachial SBP or PP to predict all-cause mortality or incident CVD over time. However, we did not assess the relative value of central versus peripheral blood pressure in this relationship. Additionally, we have found that the highest stiffness group is the most significantly related to adverse outcome, with an unevenly graded relationship between outcome and degree of stiffness in intermediate stiffness categories. We found the comparison of the highest and lowest quintiles of AAD to be consistently and strongly different over time in relation to outcome, whereas quintiles 2 through 4 exhibited some degree of crossing between cumulative event curves in the initial half of the follow-up period.
Although direct comparison is not possible with results from the meta-analysis of Vlachopoulos et al. (7) on predicting all-cause mortality and incident CVD because of differing predictor variables (PWV vs. AAD), categorization, and adjustment, it is interesting to note that our findings are consistent. In particular, the relative risk for all-cause mortality was 1.9 (95% CI: 1.60 to 2.24) in their study versus an HR of 2.3 in the present study. In contrast, however, they found marked stiffness to confer higher risk in the subgroup with a higher baseline risk than in low-risk individuals. This can be explained by the notably different definition of risk and sample selection. Indeed, the high-risk group in the Framingham cohort included subjects with known coronary artery disease, renal disease, hypertension, and diabetes, whereas our large sample of the MESA cohort, although representative of MESA participants overall, included participants without overt CVD, fewer subjects with diabetes, and no participants with end-stage renal disease. Compared with results by Maroules et al. (11) using CMR imaging in a general population sample of the Dallas Heart Study, HRs relating AAD to CV outcome were higher in our study. This may best be explained by somewhat lower power due to a relatively lower sample size (n = 2,122) and follow-up time in a generally younger cohort with lower prevalence of CV risk factors yielding fewer events than in the MESA trial. Furthermore, primary endpoint definition was significantly different between studies; the primary composite endpoint in Maroules et al. (11) included soft events (hospitalizations for unstable angina, atrial fibrillation, revascularization), whereas we focused only on hard events.
A powerful general CV risk assessment score predicting 10-year risk for CVD in the Framingham study has been established for primary care use (20). Our study showed that AAD is a strong predictor of incident CVD and, therefore, is a potentially useful risk evaluation criterion in low- to intermediate-risk individuals; its value in high-risk individuals is more limited. We found that belonging to the highest aortic stiffness category was significantly related to incident CVD, with an HR of 1.9 when the global CV risk score integrating all traditional risk factors was considered and 2.4 when individuals with 10-year CVD risk <10% was considered. Furthermore, when all risk factors were studied individually or together, AAD remained an independent predictor of CVD in the low- to intermediate-risk subcohort, albeit not among those with a baseline global risk score ≥10%.
Not all participants in the MESA study had aortic CMR images, and so our study was limited to a subgroup of 3,677 of 5,098 participants (72%) who had a CMR examination and 3,677 of 6,814 (54%) of the whole MESA cohort. Risk factors were slightly less prevalent in the subgroup of MESA participants with aortic distensibility data compared with other participants. Nevertheless, this remains the largest reported sample of proximal aorta distensibility using CMR imaging in any population. Additionally, the semi-automated contour registration process used to determine aortic areas during the cardiac cycle required a degree of manual intervention, and future studies may benefit from automated segmentation methods. Finally, the number of events remains relatively low and available data lack the statistical power to allow us to discriminate the potential predictive value of AAD for individual events such as HF in this cohort.
Decreased AAD significantly predicted all-cause mortality and incident CVD events among individuals without overt CVD. The predictive value of proximal aortic stiffness for CVD was highest in subjects with low to intermediate global CV risk in whom risk evaluation could be useful. These findings support the hypothesis that the loss of proximal aortic distensibility is an important early marker of the vascular aging continuum intertwined with atherosclerosis leading to subclinical target organ damage and ultimately increased morbidity and mortality.
COMPETENCY IN MEDICAL KNOWLEDGE: Proximal aortic stiffness can be assessed by cardiac magnetic resonance imaging and is an important determinant of circulatory efficiency. Alterations in proximal aortic function are an early marker of cardiovascular aging, atherosclerosis, and other forms of cardiovascular disease.
TRANSLATIONAL OUTLOOK: Longitudinal studies are needed to assess the relative value of various indexes of aortic and vascular function, including distensibility, as predictors of clinical outcomes.
The authors thank the other investigators, the staff, and the participants of MESA for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.
MESA was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. Dr. Duprez has received research grants from Sanofi, Regeneron, and Pfizer; and served on advisory boards for AstraZeneca and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- ascending aorta distensibility
- ankle-brachial index
- coronary artery calcium
- cardiac magnetic resonance
- cardiovascular disease
- diastolic blood pressure
- high-density lipoprotein
- heart failure
- intima-media thickness
- left ventricular hypertrophy
- mean brachial blood pressure
- pulse pressure
- pulse wave velocity
- systolic blood pressure
- Received April 8, 2014.
- Revision received August 17, 2014.
- Accepted September 8, 2014.
- 2014 American College of Cardiology Foundation
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