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(Hypertension. 2005;45:575.)
© 2005 American Heart Association, Inc.

Original Articles

Is High Pulse Pressure a Marker of Preclinical Cardiovascular Disease?

Giovanni de Simone; Mary J. Roman; Michael H. Alderman; Maurizio Galderisi; Oreste de Divitiis; Richard B. Devereux

From the Department of Clinical and Experimental Medicine (G.d.S., M.G., O.D.), Federico II University, Naples, Italy; Division of Cardiology (G.d.S., M.J.R., R.B.D.), The New York Presbyterian Hospital–Weill Medical College of Cornell University, New York, NY; and the Department of Medicine and Epidemiology (M.H.A.), Albert Einstein College of Medicine, New York, NY.

Correspondence to Giovanni de Simone, MD, Department of Clinical and Experimental Medicine, Federico II University Hospital, via S. Pansini 5, 80131 Naples, Italy. E-mail simogi{at}unina.it

	Abstract

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This study tests the hypothesis that high brachial pulse pressure might constitute preclinical cardiovascular disease, rather than a risk factor. We studied 1250 subjects (472 nonobese normotensive [<135/80 mm Hg] and 778 untreated hypertensive). Central pulse pressure was estimated from brachial pulse pressure and age and divided by stroke volume (PP/SV). Brachial pulse pressure was considered high when >63 mm Hg, and peripheral resistance high when >90th percentile of normal distribution. Among hypertensive subjects, 34% had high resistance; among them, 33% had high brachial pulse pressure, as opposed to 147 of 516 patients (28.5%) with normal resistance (P=not significant). After adjusting for age, sex, race, body mass index, heart rate, and center, left ventricular (LV) internal dimension and mass were lower with high resistance, and higher when brachial pulse pressure was high. PP/SV was 36% higher with high resistance than with normal resistance, and higher when brachial pulse pressure was high (all P<0.0001). Factorial analysis demonstrated that associations of high brachial pulse pressure with both higher PP/SV and LV mass were independent of other pressure components. Thus, because of these associations, our hypothesis is that in hypertension, pulse pressure may be considered as a marker of preclinical cardiovascular disease, similar to LV mass and PP/SV, rather than a cardiovascular risk factor.

Key Words: hypertension, arterial • blood pressure • aging • atherosclerosis

	Introduction

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Renewed interest in pulse pressure (PP) has heightened because of increasing evidence of its association with high cardiovascular risk.^1–9 In relation to age, a wide PP may result from increased systolic blood pressure (BP), decreased diastolic BP, or both.^8,9 High systolic pressure increases vascular load (a determinant of left ventricular (LV) geometry), whereas low diastolic pressure may reduce coronary perfusion pressure, both of which provide pathophysiologic explanations for the prognostic value of PP.^10,11

Increased peripheral resistance reflects the enhanced obstacle to the blood flow opposed by arterioles and is the hallmark of arterial hypertension. In contrast, increased PP is a function of increased systolic ejection to distend conduit arteries and/or loss of the elasticity of arteries needed to accommodate ejected blood and restore arterial volume thereafter. Thus, in the natural progression of hypertension, increased PP might be consequence of atherosclerosis or arterial wall fibrosis and/or calcification and might be a marker of structural alterations of the conduit arteries. In this scenario, high PP may signify a condition more severe than elevated peripheral resistance.

Thus, in the time course of cardiovascular disease, high PP may indicate preclinical vascular disease, whereas arterial hypertension is the risk factor for the development of such preclinical disease.¹² Accordingly, this study has been designed to test the hypothesis that high PP is a marker of "preclinical cardiovascular disease,"¹² independent of the level of total peripheral resistance. If confirmed, this hypothesis might refine understanding of the clinical impact of high PP on cardiovascular risk and modify risk stratification.

	Methods

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From 2 centers, we studied 1504 adults without prevalent cardiovascular disease: 942 were Americans (474 hypertensive subjects from a worksite-based study and 468 normotensive volunteers) and 562 were Italians (306 hypertensive subjects seen in the outpatient clinic and 256 normotensive volunteers). Detailed characteristics of this composite study population have been previously reported.^13–18 Hypertensive participants were under pharmacological wash-out (for at least 2 weeks) or previously untreated for arterial hypertension. Overweight and obesity were classified according to 1998 National Institutes of Health Guidelines.¹⁹ For the purpose of this study, we selected a nonobese control group (body mass index [BMI] <30 kg/m²) with normal BP (ie, <130/85 mm Hg),²⁰ resulting in a study population of 1250 individuals, including the hypertensive participants.

Echocardiographic Methods
Echocardiograms were obtained using standardized acquisition methods used in multiple studies from the 2 echocardiography laboratories.^17,18,21,22

Measurements were made as previously reported,^17,18,22 from 2-dimensional targeted M-mode echo paper tracings according to the recommendations of the American Society of Echocardiography.²³ LV mass was calculated by adjusted American Society of Echocardiography method²⁴ and normalized for height^2.7.¹³ Relative wall thickness was calculated as posterior wall thickness/LV internal radius. Stroke volume was generated from LV internal systolic and diastolic diameters using z-derived method to calculate volumes.²⁵ Cardiac output and total peripheral resistance (TPR) were also computed by standard formulas.

BP
BP was measured at the end of the echo examination. A brachial (_brachial) PP >63 mm Hg was considered abnormal, because this value has been shown to predict adverse prognosis.²⁶ Central (_central) PP was estimated from PP_brachial, using an age-adjusted equation, previously generated in 230 normotensive or hypertensive subjects:²⁷

The ratio of PP_central to stroke volume (PP/SV) was therefore computed as a marker of preclinical cardiovascular disease, which has been prognostically validated.²⁷

Statistical Analysis
Data were analyzed using SPSS 12.0 software (SPSS, Chicago, Ill). Descriptive statistics were displayed as mean±1 standard deviation or ² distributions (with Monte Carlo estimation of exact probability values). Distribution of TPR was obtained in the normal population and the 90th percentile was used to define a subgroup of hypertensive subjects with high peripheral resistance (>1988 dynes/sec per cm^–5). TPR and PP_brachial were examined using 2-factor ANCOVA, adjusting for age, BMI, sex, race, heart rate, and country. Principal component analysis was used to assess whether PP_brachial was related to markers of preclinical cardiovascular disease independent of other pressure components.²⁸

Factorial analysis with extraction of principal components was performed to analyze variance components among variables with high level of collinearity (age, BMI, heart rate, total peripheral resistance, PP_brachial, systolic and diastolic blood pressure). A correlation matrix method was used and factors with eigenvalues greater than 0.8 were identified. A scree plot was used to visualize whether the identified cutoff eigenvalues allowed the extraction of main factors (principal components) accounting for most of variance. For each observation and each extracted component, the component score was computed. The resulting component score variables, representative of the 7 variables used in the analysis, could be used, without any collinearity, in place of all original variables in multiple linear regression models with LV mass and PP/SV as dependent variables, with negligible loss of information. To assess multicollinearity, every covariate was related to all other covariates in the model and the coefficient of determination (r²) was computed. Tolerance was calculated as the reciprocal of the coefficient of determination (1–r²) of every independent variable, as a measure of unexplained variance. A tolerance 0.80 can be considered near optimal, as indicative of a level of collinearity that cannot remarkably affect stability of results.

	Results

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Table 1 summarizes characteristics of the study population. Hypertensive subjects were older and heavier than normotensive individuals, had higher mean heart rate, and included higher proportions of men, nonwhite, and overweight/obese individuals (Table 1).

View this table: [in this window] [in a new window]   TABLE 1. Characteristics of Normotensive and Hypertensive Participants

Among hypertensive patients, 264 (34%) had high TPR, and among them 88 (33%) had also high PP_brachial, as opposed to 147 of 514 patients (28.5%) with normal TPR (P>0.15).

Table 2 shows that hypertensive patients with high TPR were older than those with normal TPR, and within these groups those with high PP_brachial were the oldest. BMI was lower in patients with high TPR, whereas no effect was found for high PP_brachial.

View this table: [in this window] [in a new window]   TABLE 2. Characteristics of Groups With Normal or High Pulse Pressure in Relation to Normal or High Peripheral Resistance

LV Geometry and PP/SV Ratio
The Figure shows that after adjusting for covariates, LV diastolic dimension and LV mass were lower in patients with high TPR than in those with normal TPR, and higher in those with high than with normal PP_brachial. Parallel results with similar statistical significance were observed for LV mass index in g/m^2.7. Relative wall thickness, the index of LV concentricity, was higher with high than with normal TPR, whereas there was no association with high PP_brachial.

View larger version (30K): [in this window] [in a new window]   LV diameter (upper left panel), mass (upper right panel), relative wall thickness (lower left panel), and pulse pressure to stroke volume ratio (PP/SV, lower right panel) in relation to magnitude of total peripheral resistance (TPR) and pulse pressure (PPb) after adjustment for age, sex, race, heart rate, country, and BMI. Gray bars represent normal PPb and black bars are high PPb. No interaction was found.

The ratio PP/SV was substantially higher, by an average 36%, in subjects with high TPR than in those with normal TPR (Figure) and within groups with normal or high TPR, it was significantly higher when PP_brachial was high.

Analyses Using Continuous Variables
To assess the interaction among all variables of interest, independent of predetermined cutoff points, multiple regression models were generated in the whole population (including normotensive and hypertensive subjects) to examine independent correlates of LV mass and PP/SV. Because of the high collinearity among potential independent correlates of these 2 markers of preclinical cardiovascular disease, factorial analysis was performed to extract principal components from primary predictors of both LV mass and PP/SV (age, BMI, heart rate, total peripheral resistance, PP_brachial, and systolic and diastolic BP). The estimates of the variance in each variable accounted for by the components, defined "communalities," were between 0.83 and 0.97, with only age having a lower value (0.63), indicating that the extracted components represented the primary predictors well. Based on the predefined eigen value (0.8), 4 extracted components explained 86% of the variability of the original 7 predictors, with only a 14% loss of information.

The component matrix helped to determine what the components represented (Table 3). The first component was most highly correlated with age, PP_brachial, and systolic BP. However, age and PP_brachial better represented this component than systolic BP, because they were less correlated with the other 3 components, whereas systolic BP was similarly represented in the second component. The second component was most highly correlated with total peripheral resistance, systolic BP, and diastolic BP, but only diastolic BP showed weak correlations with the other 3 components. The third component was most highly correlated with heart rate and total peripheral resistance, but only heart rate well-represented this component, because it did not show correlations with other components. The fourth component was most highly correlated with BMI.

View this table: [in this window] [in a new window]   TABLE 3. Rotated Component Matrix of Principal Component Extraction, Performed on Age, BMI, Heart Rate, Total Peripheral Resistance, Brachial Pulse Pressure, and Systolic and Diastolic Blood Pressure

These component scores were used to model regression equations for LV mass and PP/SV, together with gender (1=male, 2=female), country (1=Italy, 2=US), and ethnicity (1=white, 2=nonwhite). As expected, the level of tolerance of regression models was excellent, because multicollinearity was eliminated (Table 4). Table 4 shows that LV mass was independently related to male gender and the first, second, and fourth components, but not with the third component (most representative of heart rate). In contrast, all components were independently related to PP/SV, with the strongest association with factors representative of aging, PP_brachial, and diastolic BP. When a categorical variable indicating the presence or the absence of arterial hypertension was also included in the regression model, the results were substantially confirmed (not shown), but a collinearity was evident between hypertension status and the second component, most representative of diastolic BP.

View this table: [in this window] [in a new window]   TABLE 4. Independent Correlates of LV Mass and PP/SV in Multiple Regression Models Using Principal Components of Variance of Age, BMI, Heart Rate, Total Peripheral Resistance, PPbrachial, and Systolic and Diastolic Blood Pressure

	Discussion

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There is a large literature on PP, which is often identified as an independent cardiovascular risk factor.^1–9,29 Inconsistent findings are found on whether this prognostic effect is related to systolic BP, a problem that is more relevant on epidemiological than on pathophysiological ground.³⁰ This apparent inconsistency is caused by different age-related peripheral amplification of central systolic pressure, because in young people magnitude of PP depends on levels of systolic BP, whereas in older populations diastolic BP is a stronger determinant.^9,31 Franklin et al⁸ demonstrated that the prognostic effect of brachial PP on coronary heart disease was stronger than that of systolic BP. At each level of systolic BP, the risk was in fact higher when diastolic BP was lower, suggesting more severe arterial stiffness. This concept is generally accepted, although not unequivocally proven, in human studies.^32–35 There is evidence of association of brachial PP with structural abnormalities of conduit arteries,^2,7,9,36,37 and there is evidence that both PP and other measures more directly associated with arterial stiffness share a similar pattern of relations with cardiovascular risk factors and prediction of mortality.^2,37,38

In this study, hypertensive individuals were divided on the basis of both the resistance element and the pulsatile element of the arterial tree, with the hypothesis that elevation of the pulsatile element defines more severe injury of the arterial tree. Our assumption has been that high brachial PP is not a cardiovascular risk factor (ie, cause of disease), such as arterial hypertension, but rather a marker of preclinical cardiovascular disease (ie, consequence of exposure), that is mathematically related to systolic and/or diastolic BP, but substantially depends on progressive impairment of arterial function. One limitation of this assumption is in the matching of the directly measured pulsatile element with the resistance element, which is computed from indirect parameters of flow and steady pressure.

Given the aforementioned limitation, our model predicts that in the presence of either normal or high peripheral resistance, brachial PP is associated with greater increase in LV mass and PP/SV (by estimated PP_central), supporting conclusions derived from the Framingham Heart Study, in which low diastolic BP and high PP are associated with increased coronary heart disease events at each level of systolic BP.⁸ This is consistent with our regression modeling using principal components in which the component representative of PP_brachial and age exhibit strong association with LV mass and PP/SV, 2 validated predictors of cardiovascular outcome, independent of the component representative of diastolic BP.

In this analysis, PP/SV is used as a surrogate estimate of arterial stiffness and has in fact the same units as a stiffness measure (mm Hg/mL per beat). However, it should be noted that PP/SV does not reflect elastic properties of conduit arteries and it changes with BP. Thus, it would be of interest to confirm relations of PP_brachial to more direct measures of central arterial stiffness using measures that are independent of BP. Because the measure of stiffness modeled on the 2-element Windkessel (such as PP/SV) can be affected by reflected waves from periphery, when reflection site is close to the heart, direct measurements of true arterial stiffness³⁹ should validate the suggested conclusion of our analysis.

There is a potential tautology in relating PP_brachial with PP_central/SV. To minimize the mathematical tautology of this relation, we derived an estimate of PP_central, by a previously reported regression model, generated in a composite group of untreated hypertensive subjects and normotensive individuals, including age, to calculate the PP/SV ratio.²⁷ The ratio PP_central/stroke volume was much less correlated with PP_brachial (r²=0.14) than was the ratio of PP_brachial to stroke volume (r²=0.57, P<0.0001 between slopes). The biological meaning of the association of PP_brachial with PP_central/SV goes in the same direction as the association of PP_brachial with LV mass, which is not affected by these mathematical considerations.

Finally, our estimate of central PP has not been validated in groups different from the ones analyzed in our original work.²⁷ As a consequence, PP/SV ratio based on estimated central PP has not been validated directly. However, central BP by applanation tonometry has been invasively validated,^40,41 which suggests that taking into account this limitation, our estimate might be an acceptable approximation for use on epidemiological scale.

Perspectives
A brachial PP >63 mm Hg is associated with greater increases in both LV mass and a surrogate index of arterial stiffness, 2 potent and independent markers of preclinical cardiovascular disease independent of a number of physiological confounders, including level of peripheral resistance and other BP components, suggesting that high PP represents a sign of established cardiovascular damage in the setting of arterial hypertension. Accordingly, we suggest elevated brachial PP be considered a marker of established preclinical cardiovascular disease, rather than a risk factor for the development of arterial disease. Whether risk stratification can be improved, by considering PP as a marker of preclinical cardiovascular disease (and therefore to be added to the level of systolic/diastolic BP for risk stratification) ultimately needs to be proven, using more direct measures of arterial stiffness and prospective studies.

	Acknowledgments

 
Supported in part by grant 2003068470/2005PRIN of Italian Ministry of Instruction, University, and Research.

Received September 19, 2004; first decision October 16, 2004; accepted January 24, 2005.

	References

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1. Tozawa M, Iseki K, Iseki C, Takishita S. Pulse pressure and risk of total mortality and cardiovascular events in patients on chronic hemodialysis. Kidney Int. 2002; 61: 717–726.[CrossRef][Medline] [Order article via Infotrieve]
2. van Dijk RA, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Brachial artery pulse pressure and common carotid artery diameter: mutually independent associations with mortality in subjects with a recent history of impaired glucose tolerance. Eur J Clin Invest. 2001; 31: 756–763.[CrossRef][Medline] [Order article via Infotrieve]
3. Asmar R, Rudnichi A, Blacher J, London GM, Safar ME. Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations. Am J Hypertens. 2001; 14: 91–97.[CrossRef][Medline] [Order article via Infotrieve]
4. Vaccarino V, Holford TR, Krumholz HM. Pulse pressure and risk for myocardial infarction and heart failure in the elderly. J Am Coll Cardiol. 2000; 36: 130–138.[Abstract/Free Full Text]
5. Baguet JP, Mallion JM, Moreau-Gaudry A, Noirclerc M, Peoc’h M, Siche JP. Relationships between cardiovascular remodelling and the pulse pressure in never treated hypertension. J Hum Hypertens. 2000; 14: 23–30.[CrossRef][Medline] [Order article via Infotrieve]
6. Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Pede S, Porcellati C. Ambulatory pulse pressure: a potent predictor of total cardiovascular risk in hypertension. Hypertension. 1998; 32: 983–988.[Abstract/Free Full Text]
7. Matthews KA, Owens JF, Kuller LH, Sutton-Tyrrell K, Lassila HC, Wolfson SK. Stress-induced pulse pressure change predicts women’s carotid atherosclerosis. Stroke. 1998; 29: 1525–1530.[Abstract/Free Full Text]
8. Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study. Circulation. 1999; 100: 354–360.[Abstract/Free Full Text]
9. Franklin SS. Cardiovascular risks related to increased diastolic, systolic and pulse pressure. An epidemiologist’s point of view. Pathol Biol (Paris). 1999; 47: 594–603.[Medline] [Order article via Infotrieve]
10. Verdecchia P, Schillaci G, Reboldi G, Franklin SS, Porcellati C. Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension. Circulation. 2001; 103: 2579–2584.[Abstract/Free Full Text]
11. Haider AW, Larson MG, Franklin SS, Levy D. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med. 2003; 138: 10–16.[Abstract/Free Full Text]
12. Devereux RB, Alderman MH. Role of preclinical cardiovascular disease in the evolution from risk factor exposure to development of morbid events. Circulation. 1993; 88 (4 Pt 1): 1444–1455.[Abstract/Free Full Text]
13. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, Alderman MH. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol. 1992; 20: 1251–1260.[Abstract]
14. de Simone G, Devereux RB, Roman MJ, Alderman MH, Laragh JH. Relation of obesity and gender to left ventricular hypertrophy in normotensive and hypertensive adults. Hypertension. 1994; 23: 600–606.[Abstract/Free Full Text]
15. de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol. 1995; 25: 1056–1062.[Abstract]
16. de Simone G, Devereux RB, Kimball TR, Mureddu GF, Roman MJ, Contaldo F, Daniels SR. Interaction between body size and cardiac workload: influence on left ventricular mass during body growth and adulthood. Hypertension. 1998; 31: 1077–1082.[Abstract/Free Full Text]
17. de Simone G, Greco R, Mureddu G, Romano C, Guida R, Celentano A, Contaldo F. Relation of left ventricular diastolic properties to systolic function in arterial hypertension. Circulation. 2000; 101: 152–157.[Abstract/Free Full Text]
18. Celentano A, Palmieri V, Esposito ND, Pietropaolo I, Crivaro M, Mureddu GF, Devereux RB, de Simone G. Inappropriate left ventricular mass in normotensive and hypertensive patients. Am J Cardiol. 2001; 87: 361–363.[CrossRef][Medline] [Order article via Infotrieve]
19. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults–The Evidence Report. National Institutes of Health. Obes Res. 1998; 6 (Suppl 2): 51S–209S.[Medline] [Order article via Infotrieve]
20. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr., Jones DW, Materson BJ, Oparil S, Wright JT, Jr., Roccella EJ. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003; 289: 2560–2572.[Abstract/Free Full Text]
21. Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Wood EA, Howard BV, Welty TK, Lee ET, Fabsitz RR. Relations of Doppler stroke volume and its components to left ventricular stroke volume in normotensive and hypertensive Am Indians: the Strong Heart Study. Am J Hypertens. 1997; 10: 619–628.[CrossRef][Medline] [Order article via Infotrieve]
22. Devereux RB, Roman MJ. Evaluation of cardiac function and vascular structure and function by echocardiography and other noninvasive techniques. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis, and Management. New York: Raven Press Ltd, 1995; 1969–1985.
23. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978; 58: 1072–1083.[Abstract/Free Full Text]
24. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986; 57: 450–458.[CrossRef][Medline] [Order article via Infotrieve]
25. de Simone G, Devereux RB, Ganau A, Hahn RT, Saba PS, Mureddu GF, Roman MJ, Howard BV. Estimation of left ventricular chamber and stroke volume by limited M-mode echocardiography and validation by two-dimensional and Doppler echocardiography. Am J Cardiol. 1996; 78: 801–807.[CrossRef][Medline] [Order article via Infotrieve]
26. Madhavan S, Ooi WL, Cohen H, Alderman MH. Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction. Hypertension. 1994; 23: 395–401.[Abstract/Free Full Text]
27. de Simone G, Roman MJ, Koren MJ, Mensah GA, Ganau A, Devereux RB. Stroke volume/pulse pressure ratio and cardiovascular risk in arterial hypertension. Hypertension. 1999; 33: 800–805.[Abstract/Free Full Text]
28. Darne B, Girerd X, Safar M, Cambien F, Guize L. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality. Hypertension. 1989; 13: 392–400.[Abstract/Free Full Text]
29. Safar ME. Pulse pressure in essential hypertension: clinical and therapeutical implications. J Hypertens. 1989; 7: 769–776.[CrossRef][Medline] [Order article via Infotrieve]
30. Safar ME, London GM. Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension. The Clinical Committee of Arterial Structure and Function. Working Group on Vascular Structure and Function of the European Society of Hypertension. J Hypertens. 2000; 18: 1527–1535.[CrossRef][Medline] [Order article via Infotrieve]
31. Franklin SS, Weber MA. Measuring hypertensive cardiovascular risk: the vascular overload concept. Am Heart J. 1994; 128: 793–803.[CrossRef][Medline] [Order article via Infotrieve]
32. Van Bortel LM, Struijker-Boudier HA, Safar ME. Pulse pressure, arterial stiffness, and drug treatment of hypertension. Hypertension. 2001; 38: 914–921.[Abstract/Free Full Text]
33. Safar M, Chamiot-Clerc P, Dagher G, Renaud JF. Pulse pressure, endothelium function, and arterial stiffness in spontaneously hypertensive rats. Hypertension. 2001; 38: 1416–1421.[Abstract/Free Full Text]
34. O’Rourke M. Arterial stiffness, systolic blood pressure, and logical treatment of arterial hypertension. Hypertension. 1990; 15: 339–347.[Abstract/Free Full Text]
35. Dart AM, Kingwell BA. Pulse pressure–a review of mechanisms and clinical relevance. J Am Coll Cardiol. 2001; 37: 975–984.[Abstract/Free Full Text]
36. de Simone G, McClelland R, Gottdiener JS, Celentano A, Kronmal RA, Gardin JM. Relation of hemodynamics and risk factors to ventricular-vascular interactions in the elderly: the Cardiovascular Health Study. J Hypertens. 2001; 19: 1893–1903.[CrossRef][Medline] [Order article via Infotrieve]
37. Viazzi F, Leoncini G, Parodi D, Ravera M, Ratto E, Vettoretti S, Tomolillo C, Sette MD, Bezante GP, Deferrari G, Pontremoli R. Pulse pressure and subclinical cardiovascular damage in primary hypertension. Nephrol Dial Transplant. 2002; 17: 1779–1785.[Abstract/Free Full Text]
38. Wilkinson IB, Prasad K, Hall IR, Thomas A, MacCallum H, Webb DJ, Frenneaux MP, Cockcroft JR. Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia. J Am Coll Cardiol. 2002; 39: 1005–1011.[Abstract/Free Full Text]
39. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE. Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens. 2002; 15: 426–444.[CrossRef][Medline] [Order article via Infotrieve]
40. Kelly R, Fitchett D. Noninvasive determination of aortic input impedance and external left ventricular power output: a validation and repeatability study of a new technique. J Am Coll Cardiol. 1992; 39: 952–963.
41. Chen CH, Ting CT, Nussbacher A, Nevo E, Kass DA, Pak P, Wang SP, Chang MS, Yin FC. Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure. Hypertension. 1996; 27: 168–175.[Abstract/Free Full Text]

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