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Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:2046-2050
doi: 10.1161/hq1201.100226
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:2046.)
© 2001 American Heart Association, Inc.


Atherosclerosis and Lipoproteins

Aortic Pulse Wave Velocity Predicts Cardiovascular Mortality in Subjects >70 Years of Age

S. Meaume; A. Benetos; O.F. Henry; A. Rudnichi; M.E. Safar

From the Geriatrics Departments of Charles-Foix Hospital (S.M., A.L., C.B.) and Emile Roux Hospital (O.F.H.), Limeil-Brevannes; the Department of Internal Medicine (M.E.S.) and INSERM U337 (A.B.), Broussais Hospital, Paris; and Co Source Outsourcing Services (A.R.), COVANCE, Rueil-Malmaison, France.

Correspondence to Professeur Michel Safar, Médecine Interne 1, Hôpital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France. E-mail michel.safar{at}brs.ap-hop-paris.fr


*    Abstract
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Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular mortality in subjects with essential hypertension and in patients with end-stage renal disease. Its contribution to cardiovascular risk in subjects 70 to 100 years old has never been tested. A cohort of 141 subjects (mean±SD age, 87.1±6.6 years) was studied in 3 geriatrics departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured with a validated automatic device. During the 30-month follow-up, 56 patients died (27 from cardiovascular events). Logistic regressions indicated that age (P=0.005) and a loss of autonomy (P=0.01) were the best predictors of overall mortality. For cardiovascular mortality, aortic PWV was the major risk predictor (P=0.016). The odds ratio was 1.19 (95% confidence interval, 1.03 to 1.37). Antihypertensive drug treatment and blood pressure, including systolic and pulse pressure, had no additive role. In subjects 70 to 100 years old, aortic PWV is a strong, independent predictor of cardiovascular death, whereas systolic or pulse pressure was not. This prospective result will need to be confirmed in an intervention trial.


Key Words: very old (>70 years) subjects • aortic pulse wave velocity • cardiovascular mortality • drug treatment of hypertension • pulse pressure


*    Introduction
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With increasing age, there is a gradual shift from diastolic blood pressure (DBP) to systolic blood pressure (SBP) and then to pulse pressure (PP) as predictors of cardiovascular (CV) risk, mainly from coronary heart disease. In patients <50 years of age, DBP is the strongest CV predictor. The age range of 50 to 59 years is a transition period when all 3 BP indexes are comparable predictors, and, from 60 years of age, PP becomes superior to both SBP and DBP to predict myocardial infarction.13 In addition, because for a given ventricular ejection aortic stiffness is the major determinant of PP, increased aortic pulse wave velocity (PWV), a classic marker of arterial rigidity, has also been identified as an independent predictor of CV risk in subjects with hypertension, whether in the presence of end-stage renal disease or with preserved renal function.46 However, these epidemiological findings are limited to cohorts between 50 and 75 years of age.

BP increases with age. However, this influence of age differs markedly for SBP and DBP.7,8 Whereas SBP increases substantially with age, particularly in women after menopause, the increase of DBP with age is less pronounced. Indeed, DBP even tends to fall after 55 years of age. In the elderly, the hemodynamic pattern associating an increase in SBP and a low DBP is a characteristic feature, usually attributed to an age-related increase of arterial stiffness.7 In elderly populations, SBP and PP are usually considered the major markers of CV risk.1 However, there is no study in subjects >70 years old that would indicate whether an increase in PWV could be, in place of SBP and PP, the best independent predictor of CV mortality.

A cohort of elderly subjects recruited from 3 geriatrics departments has been investigated since 1998 to determine whether BP and PWV are significant markers of CV morbidity and mortality after 70 years of age.9 The main objective of the present study was to determine whether brachial SBP or PP and/or aortic PWV could be considered valid markers for CV death after a 30-month follow-up.


*    Methods
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Study Cohort
From June 1998 to March 2001, 182 consecutive patients were hospitalized in 3 geriatrics departments of a Paris suburb. These patients entered the hospital for rehabilitation after infectious disease, congestive heart failure, recent orthopedic or nonorthopedic surgery, recent stroke, or end-stage Parkinson’s disease.

Of the 182 subjects, only 164 agreed to participate in the study, and 23 were excluded later for technical reasons (see below). Thus, 141 subjects (103 women, 38 men) were included. Their mean age (±SD) was 87.1±6.6 years. Ninety subjects (63.8%) showed signs of dementia, most commonly caused by Alzheimer’s disease or vascular dementia involving multiple infarcts within the brain.10 The remaining causes did not exceed 5% of demented subjects.

Eighty-one subjects were considered to have normal BP, with an SBP <140 mm Hg and a DBP <90 mm Hg. Among them, 43 were receiving antihypertensive drug therapy (ADT). Sixty subjects were considered to have a high BP, defined as an SBP >=140 mm Hg and/or a DBP >=90 mm Hg. Among these 60 hypertensive subjects, 32 were receiving ADT. Finally, the 141 subjects could be divided into 4 subgroups defined by their "BP status," according to the presence or absence of high BP and/or ADT: no high BP and no ADT (n=38) (27%); no high BP and ADT (n=43) (30.5%); high BP and no ADT (n=28) (19.9%); high BP and ADT (n=32 (22.7%) Among the 75 subjects receiving ADT, the drug used were calcium antagonists (n=14), ß-blockers (n=7), diuretics (n=31), angiotensin-converting enzyme inhibitors (n=34), or miscellaneous drugs (n=5), either alone or in combination. Nitrates were being given to 92 subjects for various CV disorders, including coronary heart diseases (see below). Drug treatment was prescribed to 12 patients for dyslipidemia (drugs including statins or fibrates), and 11 patients were being medically treated for diabetes mellitus (drugs including insulin or sulfamides). Each subject or his/her family (in cases of dementia) provided written consent to participate in the study, which was approved by our institutional review board.

The Mini-Mental State Examination was used by the participating physicians to screen the patients for the presence of cognitive impairments.11 Information compiled from the questionnaire filled out at inclusion included sex, age, weight, height, body mass index, personal history of diabetes mellitus and/or of dyslipidemia, smoking habits, and use of ADT. In all cases, this information was in accord with that give by relatives and/or included in the most recent (<1 month) previous hospitalization. Causes of death (World Health Organization International Classification of Disease, ninth revision) were obtained from death certificates, hospital record forms, and autopsy data reviewed by the authors. Sudden death was defined as a witnessed death that occurred within 1 hour after the onset of acute symptoms, with no evidence that violence or accident played any role in the fatal outcome. During the follow-up period, 56 deaths were recorded, including 27 fatal CV events.

Fifty-nine patients (42%) had a past and/or present history of CV diseases (CVDs) involving atrial fibrillation (n=14), coronary heart disease (n=17), peripheral vascular disease (n=23), and cerebrovascular disease (n=29). The mean number of CVDs per patient in this population was 0.59±0.78, with 37 patients (26%) with 1 CVD, 20 (14%) with 2, and 2 (1%) with 3.

Measurements
The determinations were made at 10 AM, with each patient in a supine position. Room temperature was between 21°C and 23°C. Brachial BP was measured by using a semiautomatic BP device, the Dinamap apparatus (model 845, Criticon), after a 15-minute rest period. Five measurements, each 2 minutes long, were averaged, enabling a determination of SBP, DBP, mean blood pressure (MBP), and heart rate. After BP was measured, PWV was determined with an automatic device, the Complior (Colson), which obtained an online pulse wave recording with 2 transducers, 1 positioned at the base of the neck for the common carotid artery and the other over the femoral artery, thereby enabling automatic calculation of PWV as previously described.12,13 The validation of this automatic method and its reproducibility were reported previously.12,13 We verified in 25 subjects >70 years of age that reproducibility was 8±1%. Among the 164 patients who consented to participate in the study, 23 were excluded for technical reasons, including wandering and agitation (n=11), intensive tremor (n=5), obesity (n=3), hyperreflexia of trachea and cough (n=2), and hypertonia of the neck muscles (n=2).

Venous blood samples were obtained from the subjects after an overnight fast. Plasma was separated without delay at 4°C in a refrigerated centrifuge and stored at 4°C (for routine biochemistry analyses by standard laboratory methods) until use. Total cholesterol was determined with a Technicon Chem assay (Technicon Instruments), and HDL cholesterol was measured in the supernatant after precipitation of apolipoprotein B–containing lipoproteins with heparin-MnCl2. LDL cholesterol was calculated as previously described.5 Plasma glucose, creatinine, and albumin were measured according to standard techniques. Creatinine clearance was calculated from the Cockroft formula.

Statistical Analyses
Continuous data are expressed as mean±1 SD, and a general linear model ANOVA was used, thereby permitting adjustment according to sex to compare principal parameter means within different categories. Differences in frequency were tested by {chi}2 analysis. Explicative variables of mortality were tested first by logistic regression with adjustment on age and sex. Those that were significant (P<=0.20) were included in the final stepwise logistic regression. Survival analysis with an actuarial method was used to describe CV mortality according to classes of PWV [cut point at 17.7 m/s according to the upper decile and 20 m/s (5% of the population)] and adjusted on pertinent parameters.4,5 Delay of death in months was computed from the date at which the patients had undergone PWV determination to the date of death or the date of the last measurement (right censored). Analyses were performed with SAS software, version 6.7, under Windows NT 98. A value of P=0.05 was considered significant in double-sided tests.


*    Results
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Classification of Subjects According to CV and Overall Mortality
The demographic, clinical, and biochemical characteristics of the study cohort are reported in Table 1. Subjects who died of any cause during the study period (overall mortality) were characterized by a higher age (P=0.003), a higher incidence of a past history of myocardial infarction (P=0.005), lower creatinine clearance (P=0.08), a lower mental score (P=0.02), and loss of autonomy (P=0.01). Regarding CV mortality, subjects were characterized by a higher incidence of a past history of myocardial infarction (P=0.001); a lower creatinine clearance (P=0.06); a higher SBP (P=0.03), DBP (P=0.06), and MBP (P=0.01); a higher aortic PWV (P=0.02); and a loss in autonomy of movement (P=0.08).


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Table 1. Characteristics of the Total Population and Mean Values According to CV and Overall Mortality (Adjusted on Sex)

Logistic Stepwise Regression of CV and Overall Mortality
For total mortality, age (P=0.005) and a loss of autonomy (P=0.01) were the 2 variables to consider. Hypoalbuminemia and high C-reactive protein had no significant role in overall mortality. For CV mortality, univariate logistic analysis (Table 2) showed that only MBP (P=0.01), SBP (P=0.02), a past history of CVD (P=0.026), creatinine clearance (P=0.056), and autonomy in movement (P=0.06) had a significant link with CV mortality. When PWV was added in the final model, the role of these factors disappeared in favor of PWV (Table 3). A 1 m/s increase in PWV increased CV mortality {approx}19% (3% to 37%). During this study, adjustment according to ADT and/or nitrates did not modify the results. BP and, in particular, SBP and PP had no additive role, whether it was studied as a quantitative or a qualitative (BP status) variable.


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Table 2. Odds Ratios on CV Mortality (Adjusted on Age and Sex): Main Results of the Univariate Logistic Analysis


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Table 3. Stepwise Logistic Procedure of CV Mortality Involving Adjustments on SBP, MBP, Past History of CVD, Creatinine Clearance, Autonomy in Movement, Plasma Glucose, C-Reactive Protein, ADT, and Nitrate Administration

Regarding survival probabilities (the Figure), a high PWV (>17.7 m/s and 20 m/s) was significantly (P=0.0007, 0.0008) correlated with CV mortality. For a PWV <17 m/s, the significance disappeared (data not shown).



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CV mortality: actuarial survival curve according PWV classes.


*    Discussion
up arrowTop
up arrowAbstract
up arrowIntroduction
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*Discussion
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In this study involving 141 patients >70 years of age, we showed that aortic PWV was a major independent predictor of CV mortality and that this marker was extremely powerful, with an adjusted odd ratio of 4.60 (95% confidence interval, 1.4 to 15.7) when PWV was >17.7 m/s (Table 3). BP and, in particular, SBP and PP did not predict CV mortality in this population. For the study, we used PWV as a marker of aortic stiffness because it is related to the square root of the aortic elasticity modulus and to the thickness-radius ratio.5,12 The PWV, determined from the foot-to-foot transit time in the aorta, offers a simple, reproducible, and noninvasive evaluation of regional arterial stiffness. This noninvasive superficial measurement merely estimates the distance traveled by the pulse, and accurate measurements of this distance can only be obtained with invasive procedures. Regarding subjects >70 years of age, because arteries become longer and more convoluted, the path lengths determined from superficial linear measurements are obviously underestimated. Furthermore, aortic PWV may be considered a more reliable index than SBP itself, owing to the frequency of "pseudohypertension" in this elderly population.14 In recent years, repeatability studies, evaluations with the algorithm derived from Bland and Altman diagrams, and modern computer technology12,13 have made PWV measurements quite feasible for easily investigating aortic stiffness in clinical studies.

In the present investigation, because of the difficulty of obtaining accurate pulse wave tracings in geriatric patients, 23 subjects had to be excluded from the statistical evaluation for methodological reasons. Similarly, although in this study a significant proportion of patients had confirmed CVD, this value was probably underestimated, because "silent" myocardial ischemia or cerebrovascular disease could not be excluded on the basis of the noninvasive methods used. Finally, because age, BP, and the use of vasoactive agents such as nitrates7 might influence aortic PWV, adjustments to these parameters were widely used during this study.

In a similar population of old subjects, we had previously established on the basis of a cross-sectional design that PWV was not correlated significantly with age, thereby indicating that the PWV-age curve approximated a plateau for those >70 years and that only the classic relation between age and BP remained significant.9 Another important finding of this previous investigation was that heart rate significantly influenced PWV. Heart rate dependency on aortic stiffness has been noted previously in such populations.5,15 In the present follow-up, there was no major interference between PWV and heart rate. Furthermore, we did not observe that heart rate significantly influenced overall and CV mortality.16,17

The major finding of the present study was that PWV was a strong predictor of CV risk, independent of heart rate, BP, plasma HDL cholesterol, and dementia, even after adjustment for ADT and nitrates. At a PWV >17.7 m/s, the CV death rate was already 50%. Interestingly, in the present elderly population, BP and particularly SBP and PP did not influence CV mortality. This finding raises the question as to whether BP (mainly SBP or PP), aortic stiffness, or even a combination of both might be the best therapeutic target to reduce CV mortality in the elderly.3,18 In patients with end-stage renal disease undergoing hemodialysis, Guerin et al19 have shown that for the same MBP reduction under ADT, PWV was reduced in survivors but remained unmodified in deceased patients. It is noteworthy that in such patients, hypertension has the same clinical features as in the elderly, involving increased aortic stiffness and a disproportionate elevation of SBP over DBP.4

An interesting finding of this follow-up was that low plasma albumin and altered markers of inflammation, such as C-reactive protein, were not significant predictors of overall or CV mortality. Malnutrition and/or C-reactive protein has previously been reported to influence CV risk, particularly in atherosclerotic subjects living in underdeveloped countries and in subjects on chronic hemodialysis.2022 Although in a previous cross-sectional study we noted the possible influence of low plasma albumin on the presence of CVD,9 this finding was not confirmed by the present long-term follow-up. It is noteworthy that loss of autonomy was the main predictor of overall mortality and can mediate the occurrence of poor nutritional status and hypoalbuminemia.

Because the study was conducted in 3 geriatrics departments, several biases may have been introduced into the study population. First, 1 of the main symptoms during hospitalization was the presence of dementia. In a cross-sectional study involving subjects >70 years of age,9 because PWV was found to be negatively associated with the presence of dementia and in the present investigation, because mental score was negatively correlated with total mortality, the present results were constantly adjusted to this variable. On the other hand, in very old subjects, the diagnosis of hypertension is often difficult to assess because the term "normotensive" may either reflect good health or be considered a symptom of the severity of cancer or congestive heart failure. For this reason, in most statistical evaluations we used BP as both a quantitative and a qualitative variable, thus enabling us to classify our population into 4 different BP status groups and to thereby exclude a major role of ADT. Finally, subjects >70 years of age should be considered "survivors," and this particular aspect may have influenced some of our findings. For instance, the lack of contribution of creatinine clearance and blood glucose to overall and CV mortality might suggest that all subjects with diabetes and/or renal insufficiency were already dead. However, in the present population, wide ranges of glycemia and creatinine clearance (Table 1) were observed, suggesting that no major bias was introduced for diabetes and renal insufficiency within the present cohort and that the studied population was indeed valid.

In conclusion, the results of this investigation indicate that the increase in aortic PWV is an independent marker of CV risk in subjects >70 years of age. In this population, arterial stiffness is even a stronger marker than BP itself. Intervention studies are required to assess the validity of this noninvasive, hemodynamic measurement within the framework of CV risk.


*    Acknowledgments
 
This study was performed with the financial support of INSERM, Association Claude-Bernard, and GPH-CV. We thank Pr Moulias and Pr Piette, Heads of the Geriatrics Departments of Charles-Foix Hospital and "l’Union nationale des retraites et personnes âgées (UNRPA)," Paris, France.

Received March 28, 2001; accepted September 6, 2001.


*    References
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up arrowDiscussion
*References
 
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4. Blacher J, Guerin A, Pannier B, Marchais S, Safar M, London G. Impact of aortic stiffness on survival in end-stage renal failure. Circulation. 1999; 99: 2434–2439.[Abstract/Free Full Text]

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Arterial aging: pathophysiological principles
Vascular Medicine, November 1, 2007; 12(4): 329 - 341.
[Abstract] [PDF]


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Nephrol Dial TransplantHome page
F. Verbeke, W. Van Biesen, P. Peeters, L. M. Van Bortel, and R. C. Vanholder
Arterial stiffness and wave reflections in renal transplant recipients
Nephrol. Dial. Transplant., October 1, 2007; 22(10): 3021 - 3027.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
M. F. O'Rourke and J. Hashimoto
Mechanical Factors in Arterial Aging: A Clinical Perspective
J. Am. Coll. Cardiol., July 3, 2007; 50(1): 1 - 13.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
M. J. Roman, R. B. Devereux, J. R. Kizer, E. T. Lee, J. M. Galloway, T. Ali, J. G. Umans, and B. V. Howard
Central Pressure More Strongly Relates to Vascular Disease and Outcome Than Does Brachial Pressure: The Strong Heart Study
Hypertension, July 1, 2007; 50(1): 197 - 203.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. D. Protogerou, M. E. Safar, P. Iaria, H. Safar, K. Le Dudal, J. Filipovsky, O. Henry, P. Ducimetiere, and J. Blacher
Diastolic Blood Pressure and Mortality in the Elderly With Cardiovascular Disease
Hypertension, July 1, 2007; 50(1): 172 - 180.
[Abstract] [Full Text] [PDF]


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CirculationHome page
D. Levy, S.-J. Hwang, A. Kayalar, E. J. Benjamin, R. S. Vasan, H. Parise, M. G. Larson, T. J. Wang, J. Selhub, P. F. Jacques, et al.
Associations of Plasma Natriuretic Peptide, Adrenomedullin, and Homocysteine Levels With Alterations in Arterial Stiffness: The Framingham Heart Study
Circulation, June 19, 2007; 115(24): 3079 - 3085.
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Am. J. Respir. Crit. Care Med.Home page
R. Sabit, C. E. Bolton, P. H. Edwards, R. J. Pettit, W. D. Evans, C. M. McEniery, I. B. Wilkinson, J. R. Cockcroft, and D. J. Shale
Arterial Stiffness and Osteoporosis in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1259 - 1265.
[Abstract] [Full Text] [PDF]


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Arch OphthalmolHome page
C. A. A. Hulsman, J. R. Vingerling, A. Hofman, J. C. M. Witteman, and P. T. V.M. de Jong
Blood Pressure, Arterial Stiffness, and Open-angle Glaucoma: The Rotterdam Study
Arch Ophthalmol, June 1, 2007; 125(6): 805 - 812.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
G. F. Mitchell, M. E. Dunlap, W. Warnica, A. Ducharme, J. M. O. Arnold, J.-C. Tardif, S. D. Solomon, M. J. Domanski, K. A. Jablonski, M. M. Rice, et al.
Long-Term Trandolapril Treatment Is Associated With Reduced Aortic Stiffness: The Prevention of Events With Angiotensin-Converting Enzyme Inhibition Hemodynamic Substudy
Hypertension, June 1, 2007; 49(6): 1271 - 1277.
[Abstract] [Full Text] [PDF]


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Arch NeurolHome page
J. Roquer, A. Ois, A. Rodriguez-Campello, M. Gomis, E. Munteis, J. Jimenez-Conde, E. Cuadrado-Godia, and J. E. Martinez-Rodriguez
Atherosclerotic Burden and Early Mortality in Acute Ischemic Stroke
Arch Neurol, May 1, 2007; 64(5): 699 - 704.
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J Am Coll CardiolHome page
I. J. Kullo and A. R. Malik
Arterial Ultrasonography and Tonometry as Adjuncts to Cardiovascular Risk Stratification
J. Am. Coll. Cardiol., April 3, 2007; 49(13): 1413 - 1426.
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Clin Med ResHome page
A. R. Khoshdel, S. L. Carney, B. R. Nair, and A. Gillies
Better Management of Cardiovascular Diseases by Pulse Wave Velocity: Combining Clinical Practice with Clinical Research using Evidence-Based Medicine
Clin. Med. Res., March 1, 2007; 5(1): 45 - 52.
[Abstract] [Full Text] [PDF]


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ANGIOLOGYHome page
A. S. Fjeldstad, C. Fjeldstad, L. S. Acree, K. J. Nickel, P. S. Montgomery, P. C. Comp, T. L. Whitsett, and A. W. Gardner
The Relationship Between Arterial Elasticity and Metabolic Syndrome Features
Angiology, February 1, 2007; 58(1): 5 - 10.
[Abstract] [PDF]


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ANGIOLOGYHome page
A. D. Achimastos, S. P. Efstathiou, T. Christoforatos, T. N. Panagiotou, G. S. Stergiou, and T. D. Mountokalakis
Arterial Stiffness: Determinants and Relationship to the Metabolic Syndrome
Angiology, February 1, 2007; 58(1): 11 - 20.
[Abstract] [PDF]


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J. Appl. Physiol.Home page
K. G. Soucy, S. Ryoo, A. Benjo, H. K. Lim, G. Gupta, J. S. Sohi, J. Elser, M. A. Aon, D. Nyhan, A. A. Shoukas, et al.
Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness
J Appl Physiol, December 1, 2006; 101(6): 1751 - 1759.
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Eur Heart JHome page
S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio, D. Hayoz, B. Pannier, C. Vlachopoulos, I. Wilkinson, H. Struijker-Boudier, et al.
Expert consensus document on arterial stiffness: methodological issues and clinical applications
Eur. Heart J., November 1, 2006; 27(21): 2588 - 2605.
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HeartHome page
C Vlachopoulos, K Aznaouridis, and C Stefanadis
Clinical appraisal of arterial stiffness: the Argonauts in front of the Golden Fleece
Heart, November 1, 2006; 92(11): 1544 - 1550.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
C. M. McEniery, S. Wallace, I. S. Mackenzie, B. McDonnell, Yasmin, D. E. Newby, J. R. Cockcroft, and I. B. Wilkinson
Endothelial Function Is Associated With Pulse Pressure, Pulse Wave Velocity, and Augmentation Index in Healthy Humans
Hypertension, October 1, 2006; 48(4): 602 - 608.
[Abstract] [Full Text] [PDF]


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CirculationHome page
K. M. Maki-Petaja, F. C. Hall, A. D. Booth, S. M.L. Wallace, Yasmin, P. W.P. Bearcroft, S. Harish, A. Furlong, C. M. McEniery, J. Brown, et al.
Rheumatoid Arthritis Is Associated With Increased Aortic Pulse-Wave Velocity, Which Is Reduced by Anti-Tumor Necrosis Factor-{alpha} Therapy
Circulation, September 12, 2006; 114(11): 1185 - 1192.
[Abstract] [Full Text] [PDF]


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Rheumatology (Oxford)Home page
T. K. Tso, W.-N. Huang, H.-Y. Huang, and C.-K. Chang
Relationship of plasma interleukin-18 concentrations to traditional and non-traditional cardiovascular risk factors in patients with systemic lupus erythematosus
Rheumatology, September 1, 2006; 45(9): 1148 - 1153.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
Yasmin, C. M. McEniery, K. M. O'Shaughnessy, P. Harnett, A. Arshad, S. Wallace, K. Maki-Petaja, B. McDonnell, M. J. Ashby, J. Brown, et al.
Variation in the Human Matrix Metalloproteinase-9 Gene Is Associated With Arterial Stiffness in Healthy Individuals
Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1799 - 1805.
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J. Am. Soc. Nephrol.Home page
E. Kimoto, T. Shoji, K. Shinohara, S. Hatsuda, K. Mori, S. Fukumoto, H. Koyama, M. Emoto, Y. Okuno, and Y. Nishizawa
Regional Arterial Stiffness in Patients with Type 2 Diabetes and Chronic Kidney Disease
J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2245 - 2252.
[Abstract] [Full Text] [PDF]


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Postgrad. Med. J.Home page
B Jani and C Rajkumar
Ageing and vascular ageing.
Postgrad. Med. J., June 1, 2006; 82(968): 357 - 362.
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J. Appl. Physiol.Home page
Yasmin, I. B. Wilkinson, K. M. O'Shaughnessy, T. Lanne, R. De Basso, and J. T. Powell
Influence of fibrillin-1 genotype on aortic stiffness in men: a note of caution
J Appl Physiol, April 1, 2006; 100(4): 1431 - 1432.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. M. Dart, C. D. Gatzka, B. A. Kingwell, K. Willson, J. D. Cameron, Y.-L. Liang, K. L. Berry, L. M.H. Wing, C. M. Reid, P. Ryan, et al.
Brachial Blood Pressure But Not Carotid Arterial Waveforms Predict Cardiovascular Events in Elderly Female Hypertensives
Hypertension, April 1, 2006; 47(4): 785 - 790.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
R. M. Fitch, J. C. Rutledge, Y.-X. Wang, A. F. Powers, J.-L. Tseng, T. Clary, and G. M. Rubanyi
Synergistic effect of angiotensin II and nitric oxide synthase inhibitor in increasing aortic stiffness in mice
Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1190 - H1198.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
E. Dolan, L. Thijs, Y. Li, N. Atkins, P. McCormack, S. McClory, E. O'Brien, J. A. Staessen, and A. V. Stanton
Ambulatory Arterial Stiffness Index as a Predictor of Cardiovascular Mortality in the Dublin Outcome Study
Hypertension, March 1, 2006; 47(3): 365 - 370.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. Paini, P. Boutouyrie, D. Calvet, A.-I. Tropeano, B. Laloux, and S. Laurent
Carotid and Aortic Stiffness: Determinants of Discrepancies
Hypertension, March 1, 2006; 47(3): 371 - 376.
[Abstract] [Full Text] [PDF]


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CirculationHome page
F. U.S. Mattace-Raso, T. J.M. van der Cammen, A. Hofman, N. M. van Popele, M. L. Bos, M. A.D.H. Schalekamp, R. Asmar, R. S. Reneman, A. P.G. Hoeks, M. M.B. Breteler, et al.
Arterial Stiffness and Risk of Coronary Heart Disease and Stroke: The Rotterdam Study
Circulation, February 7, 2006; 113(5): 657 - 663.
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Am. J. Physiol. Heart Circ. Physiol.Home page
M. C. H. Leung, I. T. Meredith, and J. D. Cameron
Aortic stiffness affects the coronary blood flow response to percutaneous coronary intervention
Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H624 - H630.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
I. J. Kullo, L. F. Bielak, S. T. Turner, P. F. Sheedy II, and P. A. Peyser
Aortic Pulse Wave Velocity Is Associated With the Presence and Quantity of Coronary Artery Calcium: A Community-Based Study
Hypertension, February 1, 2006; 47(2): 174 - 179.
[Abstract] [Full Text] [PDF]


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LupusHome page
T K Tso, W-N Huang, H-Y Huang, and C-K Chang
Association of brachial-ankle pulse wave velocity with cardiovascular risk factors in systemic lupus erythematosus
Lupus, November 1, 2005; 14(11): 878 - 883.
[Abstract] [PDF]


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J Am Coll CardiolHome page
C. M. McEniery, Yasmin, I. R. Hall, A. Qasem, I. B. Wilkinson, J. R. Cockcroft, and on behalf of the ACCT Investigators
Normal Vascular Aging: Differential Effects on Wave Reflection and Aortic Pulse Wave Velocity: The Anglo-Cardiff Collaborative Trial (ACCT)
J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1753 - 1760.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. K. Natoli, T. L. Medley, A. A. Ahimastos, B. G. Drew, D. J. Thearle, R. J. Dilley, and B. A. Kingwell
Sex Steroids Modulate Human Aortic Smooth Muscle Cell Matrix Protein Deposition and Matrix Metalloproteinase Expression
Hypertension, November 1, 2005; 46(5): 1129 - 1134.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
J. T. Powell, R. J. Turner, M. Sian, R. Debasso, and T. Lanne
Influence of fibrillin-1 genotype on the aortic stiffness in men
J Appl Physiol, September 1, 2005; 99(3): 1036 - 1040.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
R. R. Sankatsing, S. W. Fouchier, S. de Haan, B. A. Hutten, E. de Groot, J. J.P. Kastelein, and E. S.G. Stroes
Hepatic and Cardiovascular Consequences of Familial Hypobetalipoproteinemia
Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1979 - 1984.
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Am. J. Physiol. Heart Circ. Physiol.Home page
A. K. Sista, M. K. O'Connell, T. Hinohara, S. S. Oommen, B. E. Fenster, A. J. Glassford, E. A. Schwartz, C. A. Taylor, G. M. Reaven, and P. S. Tsao
Increased aortic stiffness in the insulin-resistant Zucker fa/fa rat
Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H845 - H851.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
V. Gaillard, D. Casellas, C. Seguin-Devaux, H. Schohn, M. Dauca, J. Atkinson, and I. Lartaud
Pioglitazone Improves Aortic Wall Elasticity in a Rat Model of Elastocalcinotic Arteriosclerosis
Hypertension, August 1, 2005; 46(2): 372 - 379.
[Abstract] [Full Text] [PDF]


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CirculationHome page
G. F. Mitchell, A. L. DeStefano, M. G. Larson, E. J. Benjamin, M.-H. Chen, R. S. Vasan, J. A. Vita, and D. Levy
Heritability and a Genome-Wide Linkage Scan for Arterial Stiffness, Wave Reflection, and Mean Arterial Pressure: The Framingham Heart Study
Circulation, July 12, 2005; 112(2): 194 - 199.
[Abstract] [Full Text] [PDF]


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Am. J. Clin. Nutr.Home page
C. Williams, B. A Kingwell, K. Burke, J. McPherson, and A. M Dart
Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype
Am. J. Clinical Nutrition, July 1, 2005; 82(1): 26 - 31.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
M. Schmitt, A. Avolio, A. Qasem, C. M. McEniery, M. Butlin, I. B. Wilkinson, and J. R. Cockcroft
Basal NO Locally Modulates Human Iliac Artery Function In Vivo
Hypertension, July 1, 2005; 46(1): 227 - 231.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
M. F. O'Rourke and M. E. Safar
Relationship Between Aortic Stiffening and Microvascular Disease in Brain and Kidney: Cause and Logic of Therapy
Hypertension, July 1, 2005; 46(1): 200 - 204.
[Abstract] [Full Text] [PDF]


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CirculationHome page
K. Sutton-Tyrrell, S. S. Najjar, R. M. Boudreau, L. Venkitachalam, V. Kupelian, E. M. Simonsick, R. Havlik, E. G. Lakatta, H. Spurgeon, S. Kritchevsky, et al.
Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults
Circulation, June 28, 2005; 111(25): 3384 - 3390.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
J. M. Dijk, A. Algra, Y. van der Graaf, D. E. Grobbee, M. L. Bots, and on behalf of the SMART study group
Carotid stiffness and the risk of new vascular events in patients with manifest cardiovascular disease. The SMART study
Eur. Heart J., June 2, 2005; 26(12): 1213 - 1220.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. B. Keogh, J. A. Grieger, M. Noakes, and P. M. Clifton
Flow-Mediated Dilatation Is Impaired by a High-Saturated Fat Diet but Not by a High-Carbohydrate Diet
Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1274 - 1279.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. A. Ahimastos, A. K. Natoli, A. Lawler, P. A. Blombery, and B. A. Kingwell
Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture
Hypertension, June 1, 2005; 45(6): 1194 - 1199.
[Abstract] [Full Text] [PDF]


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Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
Y. Fujiwara, P. H. M. Chaves, R. Takahashi, H. Amano, H. Yoshida, S. Kumagai, K. Fujita, D. G. Wang, and S. Shinkai
Arterial Pulse Wave Velocity as a Marker of Poor Cognitive Function in an Elderly Community-Dwelling Population
J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2005; 60(5): 607 - 612.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
S. J. Zieman, V. Melenovsky, and D. A. Kass
Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness
Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 932 - 943.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
J. A. Chirinos, J. P. Zambrano, S. Chakko, A. Veerani, A. Schob, H. J. Willens, G. Perez, and A. J. Mendez
Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease
Hypertension, May 1, 2005; 45(5): 980 - 985.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
B. Pannier, A. P. Guerin, S. J. Marchais, M. E. Safar, and G. M. London
Stiffness of Capacitive and Conduit Arteries: Prognostic Significance for End-Stage Renal Disease Patients
Hypertension, April 1, 2005; 45(4): 592 - 596.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
Yasmin, S. Wallace, C. M. McEniery, Z. Dakham, P. Pusalkar, K. Maki-Petaja, M. J. Ashby, J. R. Cockcroft, and I. B. Wilkinson
Matrix Metalloproteinase-9 (MMP-9), MMP-2, and Serum Elastase Activity Are Associated With Systolic Hypertension and Arterial Stiffness
Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 372 - 378.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
S. C. Millasseau, A. D. Stewart, S. J. Patel, S. R. Redwood, and P. J. Chowienczyk
Evaluation of Carotid-Femoral Pulse Wave Velocity: Influence of Timing Algorithm and Heart Rate
Hypertension, February 1, 2005; 45(2): 222 - 226.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
C. M. McEniery, M. Schmitt, A. Qasem, D. J. Webb, A. P. Avolio, I. B. Wilkinson, and J. R. Cockcroft
Nebivolol Increases Arterial Distensibility In Vivo
Hypertension, September 1, 2004; 44(3): 305 - 310.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
T. L. Medley, T. J. Cole, A. M. Dart, C. D. Gatzka, and B. A. Kingwell
Matrix Metalloproteinase-9 Genotype Influences Large Artery Stiffness Through Effects on Aortic Gene and Protein Expression
Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1479 - 1484.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
I. B. Wilkinson, S. S. Franklin, and J. R. Cockcroft
Nitric Oxide and the Regulation of Large Artery Stiffness: From Physiology to Pharmacology
Hypertension, August 1, 2004; 44(2): 112 - 116.
[Full Text] [PDF]


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CirculationHome page
S. Stork, A. W. van den Beld, C. von Schacky, C. E. Angermann, S. W.J. Lamberts, D. E. Grobbee, and M. L. Bots
Carotid Artery Plaque Burden, Stiffness, and Mortality Risk in Elderly Men: A Prospective, Population-Based Cohort Study
Circulation, July 20, 2004; 110(3): 344 - 348.
[Abstract] [Full Text] [PDF]


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StrokeHome page
J.M. Dijk, Y. van der Graaf, D.E. Grobbee, J.D. Banga, M.L. Bots, and on behalf of the SMART Study Group
Increased Arterial Stiffness Is Independently Related to Cerebrovascular Disease and Aneurysms of the Abdominal Aorta: The Second Manifestations of Arterial Disease (SMART) Study
Stroke, July 1, 2004; 35(7): 1642 - 1646.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
G. F. Mitchell, H. Parise, E. J. Benjamin, M. G. Larson, M. J. Keyes, J. A. Vita, R. S. Vasan, and D. Levy
Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study
Hypertension, June 1, 2004; 43(6): 1239 - 1245.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
Yasmin, C. M. McEniery, S. Wallace, I. S. Mackenzie, J. R. Cockcroft, and I. B. Wilkinson
C-Reactive Protein Is Associated With Arterial Stiffness in Apparently Healthy Individuals
Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 969 - 974.
[Abstract] [Full Text]


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Int J EpidemiolHome page
I. B Wilkinson and J. R Cockcroft
Commentary: Birthweight arterial stiffness and blood pressure: in search of a unifying hypothesis
Int. J. Epidemiol., February 1, 2004; 33(1): 161 - 162.
[Full Text] [PDF]


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HypertensionHome page
M. E. Safar, G. M London, and G. E. Plante
Arterial Stiffness and Kidney Function
Hypertension, February 1, 2004; 43(2): 163 - 168.
[Abstract] [Full Text] [PDF]


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CirculationHome page
G. F. Mitchell, Y. Lacourciere, J.-P. Ouellet, J. L. Izzo Jr, J. Neutel, L. J. Kerwin, A. J. Block, and M. A. Pfeffer
Determinants of Elevated Pulse Pressure in Middle-Aged and Older Subjects With Uncomplicated Systolic Hypertension: The Role of Proximal Aortic Diameter and the Aortic Pressure-Flow Relationship
Circulation, September 30, 2003; 108(13): 1592 - 1598.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
C. O'Sullivan, J. Duggan, S. Lyons, J. Thornton, M. Lee, and E. O'Brien
Hypertensive Target-Organ Damage in the Very Elderly
Hypertension, August 1, 2003; 42(2): 130 - 135.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
T. L. Medley, B. A. Kingwell, C. D. Gatzka, P. Pillay, and T. J. Cole
Matrix Metalloproteinase-3 Genotype Contributes to Age-Related Aortic Stiffening Through Modulation of Gene and Protein Expression
Circ. Res., June 13, 2003; 92(11): 1254 - 1261.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
H. J. Teede, B. P. McGrath, L. DeSilva, M. Cehun, A. Fassoulakis, and P. J. Nestel
Isoflavones Reduce Arterial Stiffness: A Placebo-Controlled Study in Men and Postmenopausal Women
Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1066 - 1071.
[Abstract] [Full Text] [PDF]


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StrokeHome page
S. Laurent, S. Katsahian, C. Fassot, A.-I. Tropeano, I. Gautier, B. Laloux, and P. Boutouyrie
Aortic Stiffness Is an Independent Predictor of Fatal Stroke in Essential Hypertension
Stroke, May 1, 2003; 34(5): 1203 - 1206.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
M. Zureik, J.-M. Bureau, M. Temmar, C. Adamopoulos, D. Courbon, K. Bean, P.-J. Touboul, A. Benetos, and P. Ducimetiere
Echogenic Carotid Plaques Are Associated With Aortic Arterial Stiffness in Subjects With Subclinical Carotid Atherosclerosis
Hypertension, March 1, 2003; 41(3): 519 - 527.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
E. Kimoto, T. Shoji, K. Shinohara, M. Inaba, Y. Okuno, T. Miki, H. Koyama, M. Emoto, and Y. Nishizawa
Preferential Stiffening of Central Over Peripheral Arteries in Type 2 Diabetes
Diabetes, February 1, 2003; 52(2): 448 - 452.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
M. S. Anthony
Phytoestrogens and Cardiovascular Disease: Where's the Meat?
Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1245 - 1247.
[Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
Y. T. van der Schouw, A. Pijpe, C. E.I. Lebrun, M. L. Bots, P. H.M. Peeters, W. A. van Staveren, S. W.J. Lamberts, and D. E. Grobbee
Higher Usual Dietary Intake of Phytoestrogens Is Associated With Lower Aortic Stiffness in Postmenopausal Women
Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1316 - 1322.
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CirculationHome page
G. F. Mitchell, J. L. Izzo Jr, Y. Lacourciere, J.-P. Ouellet, J. Neutel, C. Qian, L. J. Kerwin, A. J. Block, and M. A. Pfeffer
Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients With Systolic Hypertension: Results of the Conduit Hemodynamics of Omapatrilat International Research Study
Circulation, June 25, 2002; 105(25): 2955 - 2961.
[Abstract] [Full Text] [PDF]


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Journal of Renin-Angiotensin-Aldosterone SystemHome page
J. Blacher and M. Safar
Specific aspects of high blood pressure in the elderly
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1_suppl): S10 - S15.
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