CLINICAL STUDY: HYPERTENSION
Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension
Kathryn E. Ferrier, BSc(Hons)*,
Michael H. Muhlmann, MBBS, FRACP*,
Jean-Philippe Baguet, MD, PhD*,
James D. Cameron, MD, MEngSc*,
Garry L. Jennings, MD, FRACP*,
Anthony M. Dart, BChBM, DPhil, FRCP* and
Bronwyn A. Kingwell, PhD*,*
* Alfred and Baker Medical Unit, Baker Medical Research Institute, Melbourne, Victoria, Australia
Manuscript received July 31, 2001;
revised manuscript received December 20, 2001,
accepted January 2, 2002.
* Reprint requests and correspondence: Dr. Bronwyn Kingwell, Alfred and Baker Medical Unit, Baker Medical Research Institute, P.O. Box 6492, St. Kilda Road Central, Melbourne, Victoria 8008, Australia.
b.kingwell{at}alfred.org.au
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Abstract
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OBJECTIVES: We sought to investigate the effects of intensive cholesterol reduction on large artery stiffness and blood pressure in normolipidemic patients with isolated systolic hypertension (ISH).
BACKGROUND: Isolated systolic hypertension is associated with elevated cardiovascular morbidity and mortality and is primarily due to large artery stiffening, which has been independently related to cardiovascular mortality. Cholesterol-lowering therapy has been efficacious in reducing arterial stiffness in patients with hypercholesterolemia, and thus may be beneficial in ISH.
METHODS: In a randomized, double-blinded, cross-over study design, 22 patients with stage I ISH received three months of atorvastatin therapy (80 mg/day) and three months of placebo treatment. Systemic arterial compliance was measured noninvasively using carotid applanation tonometry and Doppler velocimetry of the ascending aorta.
RESULTS: Atorvastatin treatment reduced total and low-density lipoprotein cholesterol and triglyceride levels by 36 ± 2% (p < 0.001), 48 ± 3% (p < 0.001) and 23 ± 5% (p = 0.003), respectively, and increased high density lipoprotein cholesterol by 7 ± 3% (p = 0.03). Systemic arterial compliance was higher after treatment (placebo vs. atorvastatin: 0.36 ± 0.03 vs. 0.43 ± 0.05 ml/mm Hg, p = 0.03). Brachial systolic blood pressure was lower after atorvastatin treatment (154 ± 3 vs. 148 ± 2 mm Hg, p = 0.03), as were mean (111 ± 2 vs. 107 ± 2 mm Hg, p = 0.04) and diastolic blood pressures (83 ± 1 vs. 81 ± 2 mm Hg, p = 0.04). There was a trend toward a reduction in pulse pressure (71 ± 3 vs. 67 ± 2 mm Hg, p = 0.08).
CONCLUSIONS: Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery stiffness.
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Abbreviations and Acronyms
| | LVIDD | | ALT | | alanine aminotransferase | | AST | | aspartate aminotransferase | | DBP | | diastolic blood pressure | | HDL | | high density lipoprotein | | ISH | | isolated systolic hypertension | | LDL | | low density lipoprotein | | LVIDD | | left ventricular internal end-diastolic diameter | | LVIDS | | left ventricular internal end-systolic diameter | | MAP | | mean arterial pressure | | SAC | | systemic arterial compliance | | SBP | | systolic blood pressure | | TPR | | total peripheral resistance |
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Isolated systolic hypertension (ISH) affects 26% of the population >55 years (1), is associated with coronary and cerebrovascular events (2–5) and arises as a result of large artery stiffening (6–8). Although antihypertensive drug therapy reduces the occurrence of fatal and nonfatal events (9), large reductions in diastolic blood pressure (DBP) may potentially contribute to myocardial ischemia (10). Furthermore, although antihypertensive drugs may reduce arterial stiffness through a passive effect, few have a proven effect on the arterial structure (11).
Cholesterol lowering is an alternative therapy that may potentially target arterial stiffness, and thus blood pressure, through effects on endothelial function and arterial wall composition. A number of studies in hypercholesterolemic patients have shown improvement, particularly in peripheral artery properties, with cholesterol-lowering therapy (12–16). It is unknown whether a cholesterol reduction within the normal clinical range in patients with ISH might also reduce stiffness of the large arteries, and thereby systolic blood pressure (SBP). In a randomized, cross-over design, the current study sought to examine the effects of three months of intensive cholesterol reduction with atorvastatin (80 mg/day) on large artery stiffness and blood pressure in patients with stage I ISH.
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Methods
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All participants gave informed consent to participate in the study, which was undertaken with the approval of the Alfred Healthcare Group Ethics Committee and carried out in accordance with the Declaration of Helsinki (1989) of the World Medical Association.
Subjects.
Twenty-two patients with stage I ISH (18 men and 4 women; mean age ± SD; 60 ± 14 years) were recruited. Inclusion criteria for stage I ISH were a clinic SBP >140 mm Hg, but <170 mm Hg, and DBP <90 mm Hg. Exclusion criteria were age >80 and <18 years, low density lipoprotein (LDL) cholesterol <2.5 mmol/l, antihypertensive therapy, use of vasoactive or cholesterol-lowering medication, excess alcohol consumption (>4 standard drinks/day), smoking, coronary artery disease (based on history and examination) and other major medical illness. None of the female participants were taking hormone replacement therapy.
Study design.
At baseline, all patients had measurements of rest (supine) blood pressure, systemic arterial compliance (SAC), fasting lipid profile and cardiac structure and function (by echocardiography). In a double-blinded, randomized, cross-over study design, patients received three months of treatment with placebo and three months of therapy with atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), at a dose of 80 mg/day. All measurements, except for echocardiographic ones, were repeated in the morning after an overnight fast at three and six months.
Cardiac structure and function.
Indexes of cardiac structure and function were assessed at baseline only. Left ventricular end-diastolic posterior wall thickness, interventricular septal wall thickness at end diastole, left ventricular internal end-diastolic diameter (LVIDD) and left ventricular internal end-systolic diameter (LVIDS) were measured using the American Society of Echocardiography convention from M-mode images of the left ventricle, generated in the short-axis view at the level of the mitral chordae. Using these measurements, left ventricular mass (LVM), normalized for body surface area (LVM index), was estimated (17). Left ventricular systolic function was assessed as fractional shortening (FS), where
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Rest blood pressure and heart rate.
Three brachial artery blood pressure measurements and three heart rate measurements were made at 3-min intervals with the use of a Dinamap vital signs monitor (1846 SX Critikon, Tampa, Florida), with the subjects remaining in the supine position in a darkened, quiet room. The mean of these three values was taken to represent the rest level.
Systemic arterial compliance.
This was determined using the method of Liu et al. (18) and validated in our laboratory by Cameron and Dart (19). This method requires measurement of carotid artery pressure by applanation tonometry, using a Millar Mikro-Tip pressure transducer (SPT-301, Millar Instruments, Houston, Texas), and volumetric aortic flow (cardiac output), using a hand-held, continuous wave Doppler velocimeter with a 3.5-MHz transducer (Multi-Dopplex MD1, Huntleigh Technology, Cardiff, United Kingdom), as well as two-dimensional echocardiography for assessment of the left ventricular outflow tract area. Brachial artery pressure was obtained simultaneously with a Dinamap monitor and used to calibrate the carotid artery pressure contour using diastolic and mean pressures (19).
Biochemical analyses.
A 30-ml blood sample was taken at baseline and after each intervention for enzymatic analysis of plasma total, LDL and high-density lipoprotein (HDL) cholesterol, triglycerides and glucose, using a Cobas-Fara centrifugal analyzer (Roche Diagnostic Systems, Basel, Switzerland).
Statistics.
All data are presented as the mean value ± SEM, unless otherwise stated. All variables were compared using two-way analysis of variance for repeated measures to examine the effects of treatment (ptreatment) and order of intervention (porder) and treatment–order interaction (pinteraction). All statistical analyses were performed using SPSS, version 10.0 (SPSS Inc., Chicago, Illinois).
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Results
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The average age and body mass index of the participants were 60 ± 3 years and 28 ± 1 kg/m2, respectively (height 174 ± 2 cm; weight 83 ± 2 kg). Indexes of cardiac structure and function, including left ventricular mass (182 ± 9 g), left ventricular mass index (93 ± 4 g/m2) and fractional shortening (38 ± 1%), were all within normal ranges. Plasma glucose levels did not change with treatment (Table 1). After treatment with atorvastatin, plasma total and LDL cholesterol and triglyceride levels were reduced, whereas HDL cholesterol was increased, as compared with placebo (Table 1). In addition to being reduced by atorvastatin treatment, triglyceride levels were also significantly reduced with time (porder = 0.002) (Table 1). Cholesterol reduction was greater in those who received atorvastatin second (pinteraction = 0.05) (Table 1). There was no effect of the order of intervention, nor any treatment–order interaction, for any other variable.
Systemic arterial compliance and hemodynamic data.
After atorvastatin treatment, SAC was increased by 24 ± 9% (ptreatment = 0.03, porder = 0.48, pinteraction = 0.98) (Fig. 1). Rest SBP of the brachial artery was reduced by 6 ± 2 mm Hg (ptreatment = 0.03, porder = 0.62, pinteraction = 0.76) after atorvastatin treatment, while DBP and mean arterial pressure (MAP) were reduced by 2 ± 1 mm Hg (ptreatment = 0.04, porder = 0.19, pinteraction = 0.42) and 4 ± 2 mm Hg (ptreatment = 0.04, porder = 0.79, pinteraction = 0.99), respectively (Fig. 2). There was a trend toward reduced pulse pressure (placebo vs. atorvastatin: 71 ± 3 vs. 67 ± 2 mm Hg; ptreatment = 0.08, porder = 0.20, pinteraction = 0.44). The rest heart rate was not different between placebo and atorvastatin treatment (64 ± 2 vs. 64 ± 2 beats/min; ptreatment = 0.83, porder = 0.45, pinteraction = 0.12). Total peripheral resistance (TPR) was reduced after atorvastatin treatment (22.8 ± 1.8 vs. 18.9 ± 1.4 U; ptreatment = 0.05, porder = 0.15, pinteraction = 0.73), although there was no change in cardiac output (ptreatment = 0.12, porder = 0.67, pinteraction = 0.57). In addition, blood pressure and heart rate were not different when taken during measurement of SAC (data not shown).
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Figure 1 Systemic arterial compliance (SAC) after placebo administration (open bar) and after atorvastatin treatment (solid bar). *ptreatment = 0.03, porder = 0.48, pinteraction = 0.98). Data are presented as the mean value ± SEM.
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Figure 2 Rest blood pressure of the brachial artery after placebo administration and after atorvastatin treatment. The top portion of each bar represents systolic blood pressure (SBP); the white band in the middle represents mean arterial pressure (MAP); and the base portion of each bar represents diastolic blood pressure (DBP). Each pressure variable was analyzed in a separate two-way repeated measures analysis of variance and was significantly lower after atorvastatin treatment (*ptreatment <0.05 for SBP, DBP and MAP; both porder and pinteraction were >0.05 for all variables; see text for individual p values). Data are presented as the mean value ± SEM.
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Safety variables.
At baseline, three patients had plasma alanine aminotransferase (ALT) levels above the normal upper limit of 40 U/l, but all patients had aspartate aminotransferase (AST) levels below the normal upper limit of 50 U/l. After atorvastatin treatment, versus placebo, there was a significant rise in both ALT (27 ± 3 vs. 42 ± 6 U/l; ptreatment = 0.05, porder = 0.53, pinteraction = 0.35) and AST (24 ± 1 vs. 30 ± 3 U/l; ptreatment = 0.05, porder = 0.08, pinteraction = 0.30). Treatment increased ALT levels above 40 U/l in seven patients and AST levels above 50 U/l in two patients, but no patient was beyond three times the normal range. No patient complained of myalgia.
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Discussion
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Intensive cholesterol reduction with atorvastatin (80 mg/day) over three months reduced large artery stiffness and blood pressure in normocholesterolemic patients with stage I ISH. Total and LDL cholesterol and triglyceride levels were reduced to a similar extent, as reported in hypercholesterolemic patients (20,21), and HDL cholesterol was significantly increased by treatment. As ISH is a condition characterized by the presence of stiffened arteries (6–8), cholesterol-lowering therapy may slow progression. Furthermore, a reduction of large artery stiffness may contribute to the long-term benefits of statins, with regard to the risk of coronary events and stroke (22).
Blood pressure reduction has not previously been reported with intensive cholesterol reduction in normolipidemic patients. Furthermore, blood pressure reduction does not occur with statin treatment in hypercholesterolemic, normotensive patients (13,16,23–25). In patients with controlled hypertension who were also hypercholesterolemic, two studies found no change in blood pressure levels with additional statin treatment (26,27), whereas others demonstrated that additional statin therapy led to a greater reduction in SBP, MAP and DBP (28,29). Collectively, this suggests that statins may be more effective in lowering elevated, but not normal, blood pressure levels, regardless of cholesterol levels.
In the current study, a reduction in large artery stiffness probably underlies the reduced SBP and trend for reduced pulse pressure, however MAP fell slightly due to a reduction in TPR. As arterial stiffness is dependent on MAP (18), any reduction in MAP leads to a passive decrease in arterial stiffness, and thus may partly account for the observed arterial compliance changes. However, the reduction in MAP was small, and it is likely that the passive reduction in stiffness was also minimal, implying that atorvastatin also had direct effects on the arterial wall.
Previous studies have found that cholesterol-lowering therapy reduces arterial stiffness in the descending aorta (14) and carotid (13), femoral (12,13) and brachial (16) arteries of patients with familial hypercholesterolemia. Interestingly, only studies in which cholesterol-lowering therapy was taken for  12 months reported a reduction in arterial stiffness (13,14,16,23), as compared with a shorter six-month intervention study examining brachial artery stiffness (25). In nonfamilial hypercholesterolemic patients, four weeks of cholesterol-lowering therapy failed to alter central or descending aortic stiffness, although it did reduce stiffness from the femoral artery to the foot (15), whereas eight weeks of statin therapy had no effect on carotid, femoral or brachial artery stiffness in another study (24). The shorter period in which alterations were observed in the current study may be due to the different patient group, which, besides having higher blood pressure and stiff large arteries, had relatively normal cholesterol levels. Atorvastatin was also used at a maximal dose in the current study, and at this dose, it has greater efficacy for LDL reduction, as compared with pravastatin or simvastatin (20), which were used in some of the shorter trials (15,24,25).
Mechanisms.
Large artery stiffening in patients with ISH may relate to alterations in the extracellular matrix, changes in smooth muscle content, endothelial injury and atherosclerotic lesion formation. Favorable alterations in any of these variables could bring about improvements in arterial stiffness.
The rapid time frame for the observed pressure and arterial compliance changes is compatible with changes in endothelial function, which is improved with cholesterol-lowering therapy in patients with hypercholesterolemia (30), hypertriglyceridemia (31) and coronary artery disease (32,33) and in those who have had acute coronary syndromes (34). Benefits occur quickly, with one study reporting improvements after four weeks of therapy (35). Statins increase the availability of nitric oxide through an increase in endothelial nitric oxide synthase activity and expression (36,37) and also inhibit endothelin-1 production (38). The consequent vasodilation that occurs with an improvement in endothelial function may contribute to the reduction in MAP, and hence indirectly to the increase in arterial compliance. In addition, improved endothelial function in both the aorta and vasa vasorum (39) may directly affect large artery stiffness.
Atherosclerotic regression has been associated with improvement in arterial stiffness (40), raising the possibility that atorvastatin may modify aortic atherosclerotic lesions. Statin therapy for as little as eight weeks causes atherosclerotic plaque modification in rabbits (41–44). A reduction in platelet deposition and nitric oxide-mediated leukocyte rolling, adherence and transmigration, all the result of statin treatment, may contribute to plaque stabilization and regression (45,46). A reduction in matrix metalloproteinase expression may also contribute, because these enzymes are secreted by atheromatous cells and have been implicated in the weakening of the fibrous cap in unstable plaques (47). Statin treatment reduces matrix metalloproteinase expression in human carotid plaques (48) and rabbit aortic atheroma (49), and may therefore inhibit degradation of the elastic matrix and decrease stiffness.
Study implications.
Patients with ISH who have stiff large arteries are at an elevated risk for stroke and coronary events. The risk for the latter relates to both elevated cardiac afterload (50) and promotion of left ventricular hypertrophy (51), in addition to restricted coronary perfusion arising from low diastolic pressure (52,53). The current data indicate that in normolipidemic patients with ISH, intensive lipid-lowering therapy for three months has efficacy in targeting large artery stiffness, which is the underlying cause of ISH. Such therapy may be beneficial in slowing the progression of ISH and reducing coronary disease-associated risk. Larger clinical trials are warranted to confirm these data.
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Acknowledgments
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The authors thank Tanya Medley and Cleo Martin for their technical expertise.
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Footnotes
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Dr. Kingwell is a National Health and Medical Research Council Research Fellow, and Ms. Ferrier is supported by a postgraduate research scholarship from the National Heart Foundation of Australia. This study was supported by a Cardiovascular Lipid (CVL) Research Grant from Pfizer, West Ryde, Australia.
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1009 - 1013.
[Abstract]
[Full Text]
[PDF]
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J. S. Orr, A. L. Dengo, J. M. Rivero, and K. P. Davy
Arterial Destiffening With Atorvastatin in Overweight and Obese Middle-Aged and Older Adults
Hypertension,
October 1, 2009;
54(4):
763 - 768.
[Abstract]
[Full Text]
[PDF]
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A. M. Briones, N. Rodriguez-Criado, R. Hernanz, A. B. Garcia-Redondo, R. R. Rodrigues-Diez, M. J. Alonso, J. Egido, M. Ruiz-Ortega, and M. Salaices
Atorvastatin Prevents Angiotensin II-Induced Vascular Remodeling and Oxidative Stress
Hypertension,
July 1, 2009;
54(1):
142 - 149.
[Abstract]
[Full Text]
[PDF]
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B. Williams, P. S. Lacy, J. K. Cruickshank, D. Collier, A. D. Hughes, A. Stanton, S. Thom, H. Thurston, and for the CAFE and ASCOT Investigators
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,
January 6, 2009;
119(1):
53 - 61.
[Abstract]
[Full Text]
[PDF]
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B. A. Golomb, J. E. Dimsdale, H. L. White, J. B. Ritchie, and M. H. Criqui
Reduction in Blood Pressure With Statins: Results From the UCSD Statin Study, a Randomized Trial
Arch Intern Med,
April 14, 2008;
168(7):
721 - 727.
[Abstract]
[Full Text]
[PDF]
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S. Mangat, S. Agarwal, and C. Rosendorff
Do Statins Lower Blood Pressure?
Journal of Cardiovascular Pharmacology and Therapeutics,
June 1, 2007;
12(2):
112 - 123.
[Abstract]
[PDF]
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P. Strazzullo, S. M. Kerry, A. Barbato, M. Versiero, L. D'Elia, and F. P. Cappuccio
Do Statins Reduce Blood Pressure?: A Meta-Analysis of Randomized, Controlled Trials
Hypertension,
April 1, 2007;
49(4):
792 - 798.
[Abstract]
[Full Text]
[PDF]
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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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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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A. Harloff, C. Strecker, M. Reinhard, M. Kollum, M. Handke, M. Olschewski, C. Weiller, and A. Hetzel
Combined Measurement of Carotid Stiffness and Intima-Media Thickness Improves Prediction of Complex Aortic Plaques in Patients With Ischemic Stroke
Stroke,
November 1, 2006;
37(11):
2708 - 2712.
[Abstract]
[Full Text]
[PDF]
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E. Hulten, J. L. Jackson, K. Douglas, S. George, and T. C. Villines
The Effect of Early, Intensive Statin Therapy on Acute Coronary Syndrome: A Meta-analysis of Randomized Controlled Trials.
Arch Intern Med,
September 25, 2006;
166(17):
1814 - 1821.
[Abstract]
[Full Text]
[PDF]
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K. Douglas, P. G. O'Malley, and J. L. Jackson
Meta-Analysis: The Effect of Statins on Albuminuria
Ann Intern Med,
July 18, 2006;
145(2):
117 - 124.
[Abstract]
[Full Text]
[PDF]
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N. A.J. van der Linde, E. J.G. Sijbrands, F. Boomsma, and A. H. van den Meiracker
Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity: A Randomized Trial With Fluvastatin
Hypertension,
June 1, 2006;
47(6):
1125 - 1130.
[Abstract]
[Full Text]
[PDF]
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R. O. Halperin, H. D. Sesso, J. Ma, J. E. Buring, M. J. Stampfer, and J. Michael Gaziano
Dyslipidemia and the Risk of Incident Hypertension in Men
Hypertension,
January 1, 2006;
47(1):
45 - 50.
[Abstract]
[Full Text]
[PDF]
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H. D. Sesso, J. E. Buring, M. J. Chown, P. M Ridker, and J. M. Gaziano
A Prospective Study of Plasma Lipid Levels and Hypertension in Women
Arch Intern Med,
November 14, 2005;
165(20):
2420 - 2427.
[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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H. Fukuta, D. C. Sane, S. Brucks, and W. C. Little
Statin Therapy May Be Associated With Lower Mortality in Patients With Diastolic Heart Failure: A Preliminary Report
Circulation,
July 19, 2005;
112(3):
357 - 363.
[Abstract]
[Full Text]
[PDF]
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D. A. Kass
Ventricular Arterial Stiffening: Integrating the Pathophysiology
Hypertension,
July 1, 2005;
46(1):
185 - 193.
[Abstract]
[Full Text]
[PDF]
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G. V. Nair, L. A. Chaput, E. Vittinghoff, D. M. Herrington, and for the Heart and Estrogen/Progestin Replacement S
Pulse Pressure and Cardiovascular Events in Postmenopausal Women With Coronary Heart Disease
Chest,
May 1, 2005;
127(5):
1498 - 1506.
[Abstract]
[Full Text]
[PDF]
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G. V. Nair, D. Waters, W. Rogers, G. J. Kowalchuk, T. D. Stuckey, and D. M. Herrington
Pulse Pressure and Coronary Atherosclerosis Progression in Postmenopausal Women
Hypertension,
January 1, 2005;
45(1):
53 - 57.
[Abstract]
[Full Text]
[PDF]
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A.C. Sposito
Emerging insights into hypertension and dyslipidaemia synergies
Eur. Heart J. Suppl.,
December 1, 2004;
6(suppl_G):
G8 - G12.
[Abstract]
[Full Text]
[PDF]
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S Van Doornum, G McColl, and I P Wicks
Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis
Ann Rheum Dis,
December 1, 2004;
63(12):
1571 - 1575.
[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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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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A. M. Dart, C. D. Gatzka, J. D. Cameron, B. A. Kingwell, Y.-L. Liang, K. L. Berry, C. M. Reid, and G. L. Jennings
Large Artery Stiffness Is Not Related to Plasma Cholesterol in Older Subjects with Hypertension
Arterioscler Thromb Vasc Biol,
May 1, 2004;
24(5):
962 - 968.
[Abstract]
[Full Text]
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J. I. Osende, M. Ruiz-Ortega, L. M. Blanco-Colio, and J. Egido
Statins to prevent cardiovascular events in hypertensive patients. The ASCOT-LLA study
Nephrol. Dial. Transplant.,
March 1, 2004;
19(3):
528 - 531.
[Full Text]
[PDF]
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A. C. Sposito, S. Gonbert, E. Bruckert, M. Atassi, I. Beucler, S. Amsellem, O. Khallouf, P. Benlian, and G. Turpin
Magnitude of HDL Cholesterol Variation After High-Dose Atorvastatin Is Genetically Determined at the LDL Receptor Locus in Patients With Homozygous Familial Hypercholesterolemia
Arterioscler Thromb Vasc Biol,
November 1, 2003;
23(11):
2078 - 2082.
[Abstract]
[Full Text]
[PDF]
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A. Lerman and J. Herrmann
Endothelial function under pressure
J. Am. Coll. Cardiol.,
May 21, 2003;
41(10):
1759 - 1760.
[Full Text]
[PDF]
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J. J. Oliver and D. J. Webb
Noninvasive Assessment of Arterial Stiffness and Risk of Atherosclerotic Events
Arterioscler Thromb Vasc Biol,
April 1, 2003;
23(4):
554 - 566.
[Abstract]
[Full Text]
[PDF]
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J. R. Cockcroft and I. B. Wilkinson
reliability of transfer function in determining central pulse pressure and augmentation index: Reply
J. Am. Coll. Cardiol.,
September 18, 2002;
40(6):
1196 - 1197.
[Full Text]
[PDF]
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Abstract
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