Published online before print August 31, 2009, doi: 10.1161/HYPERTENSIONAHA.109.130914
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2009;54:1009.)
© 2009 American Heart Association, Inc.
Original Articles |
Atorvastatin Treatment Is Associated With Less Augmentation of the Carotid Pressure Waveform in Hypertension
A Substudy of the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT)
From the International Centre for Circulatory Health, Imperial College London & Imperial College Healthcare NHS Trust, London W2 1LA, UK.
Correspondence to Professor Alun D. Hughes, International Centre for Circulatory Health, NHLI, Imperial College London, St Mary’s Hospital, London W2 1LA, UK. E-mail a.hughes{at}imperial.ac.uk
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Hydroxymethylglutaryl-CoA reductase inhibitors (statins) reduce cardiovascular events in hypertensive subjects, but their effect on carotid BP, pressure augmentation, and wave reflection is unknown. We compared the effect of atorvastatin with placebo in a substudy of the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA). Hypertensive patients (n=142; age=43 to 79 years; 127 male) with total cholesterol
6.5 mmol/L were randomized to atorvastatin 10 mg or placebo. Carotid BP and flow velocity were measured by tonometry and Doppler ultrasound. Augmentation index (carotid AIx) was calculated, and waveforms were separated into backward and forward components by wave intensity analysis. Brachial BP was similar in atorvastatin and placebo groups. Carotid AIx and augmentation pressure were significantly less in patients randomized to atorvastatin (mean [SD]: 21.7 [12.1] versus 25.9 [10.3] %; P=0.027 and 10.2 [6.5] versus 13.1 [6.6] mm Hg; P=0.016, respectively), and atorvastatin treatment was associated with significantly less wave reflection from the body. Carotid systolic BP was slightly lower in the atorvastatin group, but there was a statistically significant interaction between lipid-lowering and antihypertensive regimen with lower carotid systolic BP in patients randomized to amlodipine-based therapy and atorvastatin. Carotid wave velocity, timings of waves, and wave intensities did not differ significantly between atorvastatin and placebo groups. Atorvastatin treatment is associated with less augmentation of the carotid BP waveform and less wave reflection from the body. This could contribute to the reduction in risk of cardiovascular events by statins.
Key Words: blood pressure • waves • hydroxymethylglutaryl-CoA reductase inhibitors • cholesterol • tonometry • Doppler ultrasound
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Inhibitors of hydroxymethylglutaryl CoA (statins) are widely prescribed, and there is extensive evidence showing that they prevent cardiovascular disease.1 Recently it has been suggested that statins, in addition to their ability to reduce low-density lipoprotein (LDL) cholesterol, may reduce blood pressure (BP).2,3 Further, evidence from a recent meta-analysis4 suggests that this effect is small, but could complement the primary effects of statins on serum cholesterol levels.
Measurement of brachial BP is a long-established technique, but it is recognized that brachial and central (aortic) systolic BP differ, sometimes markedly.5 These differences are proposed to arise from differences in augmentation of the systolic pressure waveform attributable to wave reflection.6 Importantly, a number of recent studies have shown that antihypertensive agents differentially affect central and brachial blood pressures,7,8 and it has been suggested that these differences could account for variations in cardiovascular outcomes between therapies. As yet, the possible effects of statins on carotid blood pressure have not been described.
The Anglo Scandinavian Cardiac Outcomes Trial (ASCOT) examined the effect of 2 antihypertensive regimens (amlodipine- versus atenolol-based) and atorvastatin on cardiovascular events using a factorial design.9 This study therefore offered an opportunity to test whether atorvastatin affected the central blood pressure, pressure augmentation, and wave reflection in the context of a large prospective randomized hypertension treatment trial.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Participants
Individuals (n=142) who were eligible for the factorial lipid-lowering arm of ASCOT (ASCOT-LLA)9,10 participated in a carotid BP substudy based at St Mary’s Hospital, London, UK. Participants had a total blood cholesterol concentration
6.5 mmol/L and were not receiving lipid lowering agents at the time of randomization. All subjects recruited into ASCOT-LLA fulfilled the criteria for inclusion in the main ASCOT study and were randomized to receive atorvastatin 10 mg daily or matching placebo. In addition, all subjects were randomized to a regimen of amlodipine with perindopril added as required, or a regimen of atenolol with bendroflumethiazide-K added as required in a factorial design.9,10 Antihypertensive treatment was titrated to achieve target blood pressures (<140/90 mm Hg for people without diabetes and <130/80 mm Hg for people with diabetes). If necessary, additional antihypertensive agents were administered according to a prespecified algorithm.109 All measurements for the substudy were performed between 12 to 18 months after randomization, when on-treatment blood pressures were relatively stable. The study was approved by the St Mary’s Hospital Research Ethics Committee and all subjects gave written informed consent.
Investigations
Brachial blood pressure was measured in the seated position after at least 5 minutes rest using a validated semiautomated device (Omron HEM 705CP, Omron). All other measurements were performed in a temperature-controlled darkened room, with subjects having rested supine for at least 10 minutes. Applanation tonometry was performed on the right common carotid using a Millar tonometer (SPT-301, Millar Instruments Inc) and calibrated to brachial artery pressure as previously described.11 Carotid tonometry was successful in all individuals. Carotid artery flow velocity measurements were made approximately 2 cm from the right carotid bulb by pulsed wave Doppler with an HDI 5000 ultrasound machine (Philips Medical Systems) equipped with a 7.5 to 10 MHz linear array transducer at a Doppler angle of 60°. Carotid pressure and flow velocity were sampled at a frequency of 200 Hz, and waveforms were ensembled using the ECG R wave as a fiducial marker. Both pressure and flow data from at least 6 cardiac cycles were acquired, digitized, and analyzed off-line using a custom-designed software package in Matlab 5.3 (Mathworks).
Echocardiography was performed on all patients using an HDI 5000 ultrasound machine. Measurements were made in accordance with the American Society of Echocardiography guidelines.12 Arterial compliance was estimated as stroke volume (SV)/carotid pulse pressure (cPP).
Blood was taken for analysis of plasma glucose and serum lipids, creatinine C-reactive protein (CRP), and serum amyloid A (SAA). Details of the analytic assays for CRP and SAA have been reported previously.13 Diabetes was diagnosed on the basis of a fasting plasma glucose of >7.0 mmol/L or a previous diagnosis of diabetes mellitus.14
Wave Intensity and Pressure Waveform Analysis
Wave intensity analysis was performed and waves were separated into forward and backward components as previously described.15,16 Local wave velocity was calculated using the pressure-velocity loop method, a validated method for measuring local wave velocity.17 Waves were quantified by measuring the integral under the wave (cumulative wave intensity) which corresponds to the total energy density carried by the wave (for further details please see http://hyper.ahajournals.org). Two principal waves originating from the heart were measured: S, the forward traveling compression wave attributable to ventricular ejection and D, the forward traveling decompression wave attributable to deceleration of ventricular contraction in protodiastole.18 Reflections returning down the carotid (ie, from the head) and up the carotid (ie, from the body) were quantified separately using the wave reflection index (WRI): the cumulative reflected wave intensity expressed as a proportion of the cumulative wave intensity of the incident wave, S. An early forward decompression wave, a rereflection of the reflected wave from the head,16 was not taken into account when calculating WRI. Augmentation index in the carotid artery (carotid AIx), the pressure difference between the first shoulder of the pressure waveform and the systolic peak expressed as a percentage of the pulse pressure was calculated from the carotid pressure waveform as described by Kelly et al.19 This has been shown to correlate highly with directly measured aortic AIx.20 Waveforms were also classified into Type A, B, and C as described by Murgo et al,21 and when the peak systolic pressure preceded a well-defined inflection point (type C) AIx was calculated as a negative value. Although AIx is an indirect measure of wave reflection and is also influenced by other factors such as heart rate, height, and arterial stiffness,22 carotid AIx and WRI showed a reasonably close correlation (r=0.40; P<0.001) suggesting that carotid AIx provides some insight into wave reflection in the absence of wave separation.
Statistics and Reproducibility
Reproducibility data have been published in detail elsewhere.18 On the basis of this and additional unpublished data in untreated hypertensive subjects we calculated that a total of 140 subjects would be required to detect a difference of 5 mm Hg in carotid SBP or 3% in carotid AIx with 90% power at the 5% significance level. As this was a factorial design, possible interactions were tested and the main effect (ie, all lipid lowering treatment versus all placebo) only analyzed if the interaction term was not significant.23 P values for interactions have not been reported if they were not statistically significant. Statistical analysis was performed using Stata 10.0 (StataCorp LP). Population characteristics are reported as mean (SD), median (interquartile range) for skewed data, or n (%) for categorical variables. Statistical comparisons of continuous data were made using a Student t test after log transformation if appropriate, and categorical data were compared using a 
2 test. Further statistical analysis was performed using multivariate analysis. In all cases P<0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The characteristics of participants at the time of the study are shown in Table 1. The 2 groups were very similar with the exception of the expected differences in total cholesterol, LDL cholesterol, and triglycerides. In particular brachial blood pressures did not differ significantly between groups. Overall the data in this substudy were similar to those seen in the lipid-lowering limb of the main ASCOT study.9
|
There was evidence of an interaction between lipid-lowering therapy and antihypertensive therapy with lower carotid systolic BP (cSBP) in individuals randomized to the combination of atorvastatin and amlodipine-based therapy (Figure). No other instances of a significant interaction between regimens were observed for any other parameters reported in Table 2, including carotid AIx PAug and measures of wave reflection.
|
|
Pressure augmentation, measured either as carotid AIx or PAug, was significantly less in people randomized to atorvastatin (Table 2). The magnitude of the pressure at the shoulder did not differ significantly between groups and the timings of the foot and shoulder of the pressure waveform were not altered by atorvastatin treatment. Both markers of inflammation, CRP and SAA, were significantly lower in individuals randomized to atorvastatin, and higher carotid AIx correlated significantly with higher CRP (r=0.13; P=0.04). The relationship between AI and SAA was similar, albeit of borderline statistical significance (r=0.11; P=0.08). After inclusion of CRP in a multivariate model with age and sex, atorvastatin treatment remained associated with a lower carotid AIx (difference between atorvastatin and placebo=4.4 [2.0]; P=0.03 after adjustment). Similar findings were observed if SAA replaced CRP in this model (data not shown).
Analysis of wave reflection showed that atorvastatin was associated with significantly less wave reflection from the body (Table 2) and less wave reflection from the head, although this latter effect was not statistically significant.
Local wave velocity, c, a measure of carotid artery stiffness, was slightly, but not significantly, lower in people randomized to atorvastatin (Table 2) and estimated arterial compliance (SV/PP) was not significantly different (Table 2). There were no significant differences between the 2 groups for either the cumulative wave energy associated with ejection, or the cumulative wave energy of the decompression wave occurring in protodiastole (Table 2).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This study has shown in a prospective randomized clinical trial that atorvastatin is associated with less pressure augmentation and wave reflection in the carotid artery in patients with well controlled hypertension. Atorvastatin also caused a small average reduction in cSBP, but this effect differed by antihypertensive regimen with a more marked reduction in cSBP in subjects randomized to the amlodipine-based regimen.
Previous individual studies have yielded conflicting data regarding the ability of statins to lower brachial blood pressure.2,3,24 However, a recent meta-analysis4 has reported that statin use is associated with an average reduction in brachial SBP of 
2 mm Hg. A previous report from ASCOT LLA2 also showed significant differences in brachial blood pressure of 0.8 to 1.1 mm Hg over the period 6 to 18 months after randomization (approximately the time of investigations in the current study). This is comparable to the 1 mm Hg lower brachial blood pressure in individuals randomized to atorvastatin in our study, albeit not statistically significant.
Atorvastatin had significant effects on pressure augmentation measured in the carotid artery and reduced wave reflection from the body. Direct measurement of carotid AIx has been shown to correlate highly with invasive measurements of AIx in the aorta20 and, as we show, correlates with a more specific measurement of wave reflection (WRI) in the carotid artery. Carotid artery tonometry, although more technically demanding, is superior to measurements derived from application of a generalized transfer function to radial waveforms because the latter technique results in a systematic underestimation of the aortic AIx,25 and central AIx derived from radial tonometry is not closely correlated with invasively measured aortic AIx.26 The effect of atorvastatin on augmentation and wave reflection may be important because there is extensive evidence that altered wave reflections have adverse effects on cardiac function through increased afterload and impaired arterio-ventricular coupling.27,28 The effect of atorvastatin on augmentation and wave reflection may be attributable to beneficial effects of statin treatment on endothelial function,29 because release of nitric oxide is an important factor in determining wave reflection arising from sites of potential impedance mismatching, such as arterial bifurcations.30 The relationship between carotid AIx and the inflammatory markers CRP and SAA suggests a possible role for inflammation in increased augmentation and wave reflection, possibly related to endothelial dysfunction. Whether the antiinflammatory effect of statins could account for the lower augmentation in the individuals treated with atorvastatin merits further study. A previous small study31 has reported that atorvastatin reduced arterial stiffness in individuals with isolated systolic hypertension, although in this case there was also a significant reduction in brachial blood pressure. Interpreting the effect of atorvastatin on cSBP is less straightforward because the existence of a significant interaction between atorvastatin and antihypertensive regimen is indicative either of a positive interaction between atorvastatin and amlodipine-based regimen or a negative (inhibitory) interaction between atenolol-based therapy and atorvastatin. Our data suggest a nonsignificant lower carotid blood pressure after randomization to atorvastatin, but the factorial design of the study precludes a definitive interpretation. Recently, another substudy of ASCOT (CAFE-LLA)32 also reported that atorvastatin had no significant effect on central blood pressure estimated using radial artery tonometry, however, the possibility of interaction between lipid lowering and antihypertensive therapy was not examined.
Our study has a number of limitations. Participants were predominantly male, and it is questionable whether these data can be extrapolated to women. Because of its factorial design, use of atorvastatin was combined with use of antihypertensive treatment, and antihypertensive drug use was up-titrated during the study to achieve similar BP targets based on measurements of brachial blood pressure. There was slightly more use of third line antihypertensive agents in the group receiving placebo, and this will have tended to obscure blood pressure differences between the groups. Measurements of blood pressure were made in the carotid artery, not the aorta. Although pressures in the aorta and carotid artery are very similar,20 wave reflection patterns differ somewhat,20 with a more prominent reflected component from the head, and a slightly lower carotid AIx.20 Because reflection from the body was more affected by atorvastatin than reflection from the head, this may also have tended to lead to an underestimation of the overall effect of atorvastatin on wave reflection. The strengths of this study are its randomized design and the comprehensive range of measurements made, including direct measurement of carotid pressure as an estimate of aortic pressure without the use of mathematical transformation using a transfer function.
Clinical Perspective
Atorvastatin treatment is associated with less augmentation of the carotid artery pressure waveform in well-controlled hypertensive individuals. This effect appears to be primarily attributable to less wave reflection. There may also be a potential beneficial interaction between atorvastatin- and amlodipine-based antihypertensive treatment on central systolic blood pressure. The beneficial effects of atorvastatin on wave reflection may contribute to its action in preventing cardiovascular disease.
|
Acknowledgments |
|---|
We are grateful to Dr Andrew Zambanini (International Centre for Circulatory Health, Imperial College London, UK) for his help with this study. We are also grateful to Dr Ruth Gallimore (Centre for Amyloidosis and Acute Phase Proteins, the Royal Free and University College Medical School, London, UK) for undertaking biochemical analyses.
Sources of Funding
The study was supported by a grant from Pfizer International. C.M. was supported by a Welcome Trust Fellowship. A.D.H., J.M., N.P., P.S.S., and S.A.McG.T. received support from the NIHR Biomedical Research Centre Funding Scheme. R.J.T. was supported by a Sidney Sax fellowship from the National Health and Medical Research Council of Australia (grant number 334173).
Disclosures
A.D.H., J.M., N.P., P.S.S., and S.A.McG.T. have served as consultants to or received travel expenses from or payment for speaking at meetings or funding for research from one or more pharmaceutical companies that market BP-lowering or lipid-lowering drugs, including Pfizer and Servier.
Received February 12, 2009; first decision March 2, 2009; accepted August 4, 2009.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003; 326: 1423.
2. Dahlof B, Poulter N, Sever PS. Do statins lower blood pressure? Evidence from the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA). Circulation. 2004; 110: 402.
3. Golomb BA, Dimsdale JE, White HL, Ritchie JB, Criqui MH. Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial. Arch Int Med. 2008; 168: 721–727.
4. Strazzullo P, Kerry SM, Barbato A, Versiero M, D'Elia L, Cappuccio FP. Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials. Hypertension. 2007; 49: 792–798.
5. Mahmud A, Feely J. Spurious systolic hypertension of youth: fit young men with elastic arteries. Am J Hypertens. 2003; 16: 229–232.[CrossRef][Medline] [Order article via Infotrieve]
6. Nichols WW, O'Rourke MF. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. IV ed. London: Edward Arnold; 1998.
7. London GM, Asmar RG, O'Rourke MF, Safar ME. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J Am Coll Cardiol. 2004; 43: 92–99.
8. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O'Rourke M. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006; 113: 1213–1225.
9. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149–1158.[CrossRef][Medline] [Order article via Infotrieve]
10. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. J Hypertens. 2001; 19: 1139–1147.[CrossRef][Medline] [Order article via Infotrieve]
11. 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; 20: 952–963.[Abstract]
12. Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davis JL, Douglas PS, Faxon DP, Gillam LD, Kimball TR, Kussmaul WG, Pearlman AS, Philbrick JT, Rakowski H, Thys DM, Antman EM, Smith SC Jr, Alpert JS, Gregoratos G, Anderson JL, Hiratzka LF, Hunt SA, Fuster V, Jacobs AK, Gibbons RJ, Russell RO. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Circulation. 2003; 108: 1146–1162.
13. Ledue TB, Weiner DL, Sipe JD, Poulin SE, Collins MF, Rifai N. Analytical evaluation of particle-enhanced immunonephelometric assays for C-reactive protein, serum amyloid A and mannose-binding protein in human serum. Ann Clin Biochem. 1998; 35: 745–753.[Medline] [Order article via Infotrieve]
14. World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva; 1999.
15. Zambanini A, Khir A, Byrd S, Parker K, Thom S, Hughes AD. Wave intensity analysis: a novel non-invasive method for determining arterial wave transmission. Comput Cardiol. 2002; 29: 717–720.
16. Zambanini A, Cunningham SL, Parker KH, Khir AW, McG Thom SA, Hughes AD. Wave-energy patterns in carotid, brachial, and radial arteries: a noninvasive approach using wave-intensity analysis. Am J Physiol Heart Circ Physiol. 2005; 289: H270–H276.
17. Khir AW, O'Brien A, Gibbs JS, Parker KH. Determination of wave speed and wave separation in the arteries. J Biomech. 2001; 34: 1145–1155.[CrossRef][Medline] [Order article via Infotrieve]
18. Parker KH, Jones CJ, Dawson JR, Gibson DG. What stops the flow of blood from the heart? Heart Vessels. 1988; 4: 241–245.[CrossRef][Medline] [Order article via Infotrieve]
19. Kelly R, Hayward C, Avolio A, O'Rourke M. Noninvasive determination of age-related changes in the human arterial pulse. Circulation. 1989; 80: 1652–1659.
20. 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.
21. Murgo JP, Westerhof N, Giolma JP, Altobelli SA. Aortic input impedance in normal man: relationship to pressure wave forms. Circulation. 1980; 62: 105–116.
22. Nichols WW. Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms. Am J Hypertens. 2005; 18: 3S–10S.[Medline] [Order article via Infotrieve]
23. McAlister FA, Straus SE, Sackett DL, Altman DG. Analysis and reporting of factorial trials: a systematic review. JAMA. 2003; 289: 2545–2553.
24. Tonelli M, Sacks F, Pfeffer M, Lopez-Jimenez F, Jhangri GS, Curhan G. Effect of pravastatin on blood pressure in people with cardiovascular disease. J Hum Hypertens. 2006; 20: 560–565.[CrossRef][Medline] [Order article via Infotrieve]
25. Chen CH, Nevo E, Fetics B, Pak PH, Chen FC. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Circulation. 1997; 95: 1827–1836.
26. Hope SA, Meredith IT, Cameron JD. Arterial transfer functions and the reconstruction of central aortic waveforms: myths, controversies and misconceptions. J Hypertens. 2008; 26: 4–7.[Medline] [Order article via Infotrieve]
27. Kelly RP, Tunin R, Kass DA. Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle. Circ Res. 1992; 71: 490–502.
28. Yano M, Kohno M, Kobayashi S, Obayashi M, Seki K, Ohkusa T, Miura T, Fujii T, Matsuzaki M. Influence of timing and magnitude of arterial wave reflection on left ventricular relaxation. Am J Physiol Heart Circ Physiol. 2001; 280: H1846–H1852.
29. Wolfrum S, Jensen KS, Liao JK. Endothelium-dependent effects of statins. Arterioscler Thromb Vasc Biol. 2003; 23: 729–736.
30. Chowienczyk PJ, Kelly RP, MacCallum H, Millasseau SC, Andersson TL, Gosling RG, Ritter JM, Anggard EE. Photoplethysmographic assessment of pulse wave reflection: blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus. J Am Coll Cardiol. 1999; 34: 2007–2014.
31. Ferrier KE, Muhlmann MH, Baguet JP, Cameron JD, Jennings GL, Dart AM, Kingwell BA. Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension. J Am Coll Cardiol. 2002; 39: 1020–1025.
32. Williams B, Lacy PS, Cruickshank JK, Collier D, Hughes AD, Stanton A, Thom S, Thurston H. Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study. Circulation. 2009; 119: 53–61.
Related Article:
Hypertension 2009 54: 958-959.
This article has been cited by other articles:
 |
|
 |
|
  J. D. Cameron Wave Intensity Analysis and Central Blood Pressure Hypertension, November 1, 2009; 54(5): 958 - 959. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||