Atherosclerosis and Lipoproteins |
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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Key Words: very old (>70 years) subjects aortic pulse wave velocity cardiovascular mortality drug treatment of hypertension pulse pressure
| Introduction |
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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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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 Alzheimers 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 Bcontaining 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
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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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
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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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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| Discussion |
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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 |
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Received March 28, 2001; accepted September 6, 2001.
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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. [Abstract] [Full Text] [PDF] |
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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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B Jani and C Rajkumar Ageing and vascular ageing. Postgrad. Med. J., June 1, 2006; 82(968): 357 - 362. [Abstract] [Full Text] [PDF] |
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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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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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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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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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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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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. [Abstract] [Full Text] [PDF] |
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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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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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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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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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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. 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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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. [Abstract] [Full Text] [PDF] |
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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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. [Abstract] [Full Text] [PDF] |
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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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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. [PDF] |
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