Reduction In Pulse Wave Velocity Research Articles

Moxonidine-based combination antihypertensive therapy in patients with metabolic syndrome

Aim.To assess the effects of moxonidine-based combination therapy on clinical status, laboratory parameters, and target organs in patients with metabolic syndrome (MS).Material and methods.In total, 60 MS patients with Stage 1-2 arterial hypertension (AH) were randomised into 3 groups. Group I was administered moxonidine (0,2-0,4 mg/d) and amlodipine (5-10 mg/d); Group II received moxonidine (0,2-0,4 mg/d) and hydrochlorothiazide (12,5 mg/d); Group III was treated with moxonidine (0,2-0,4 mg/d) and enalapril (10-20 mg/d). At baseline and after 24 weeks of treatment, the following characteristics were assessed: waist circumference (WC), body mass index (BMI), 24-hour blood pressure monitoring (BMP) parameters, left ventricular myocardial mass index (LVMMI), E/A ratio, isovolumetric relaxation time (IVRT), deceleration time (DT) of early diastolic velocity, peak Em velocity at interventricular septum and lateral wall levels, E/Em ratio (myocardial tissue Doppler echocardiography), pulse wave velocity (PWV) between descending aorta and aortic bifurcation levels (ultrasound method), and stiffness index β of ascending aorta. In addition, lipid, carbohydrate, and purine metabolism parameters were assessed; glomerular filtration rate (GFR) was calculated (MDRD method); and urine albumin levels were measured.Results.In Group I (moxonidine + amlodipine), target blood pressure (BP) levels were achieved in 70% of the patients. Systolic BP (SBP) levels, LVMMI, and DT decreased by 19,3±11,4 mm Hg, 4,4 g/m2 (p=0,09), and 10,6 ms (p<0,05), respectively. The increase in E/A ratio and Em annular velocity (Em av) reached 0,4 (p<0,05) and 1,4 cm/s (p<0,05), respectively, while E/Em av ratio decreased by 0,8 (p<0,05), and PWV decreased by 1,6 ms (p<0,05). The BMI decrease reached 0,7 kg/m2 (p<0,05). In Group II (moxonidine + hydrochlorothiazide), target BP levels were achieved in 40% of the participants, with a decrease in SBP levels by 14,7 mm Hg (p<0,05). DT was reduced by 9,4 ms (p<0,05), E/A ratio increased by 0,1 (p<0,05), while PWV, BMI, and GFR decreased by 1,3 m/s (p<0,05), 0,8 kg/m2 (p<0,05), and 5,6 ml/min/1,73 m2 (p<0,05), respectively. In Group III (moxonidine + enalapril), 60% of the patients achieved target BP levels, and SBP levels were reduced by 21,1 mm Hg (p<0,05). LVMMI decreased by 5,1 g/m2 (p<0,05), Em av increased by 0,3 cm/s (p<0,05), while the respective reduction in PWV, WC, and BMI reached 1,1 m/s (p<0,05), 1,8 cm (p<0,05), and 0,5 kg/m2 (p<0,05). All three groups demonstrated a significant reduction in urine albumin levels.Conclusion.The moxonidine-based combination therapy effectively reduced the levels of BP and urine albumin. The combination of moxonidine with amlodipine or enalapril improved cardiac structure and function, as well as renal excretory function. The combination of moxonidine and hydrochlorothiazide, however, negatively affected renal excretion. All three variants of combination therapy were metabolically neutral and demonstrated beneficial effects on visceral obesity.

Effects of nebivolol or irbesartan in combination with hydrochlorothiazide on vascular functions in newly-diagnosed hypertensive patients: The NINFE (Nebivololo, Irbesartan Nella Funzione Endoteliale) study

BackgroundArterial hypertension affects endothelial function and arterial stiffness. The angiotensin (AT1) receptor antagonist irbesartan improves endothelial function and arterial stiffness in hypertensive patients. Nebivolol, a beta1-selective beta blocker, reduces systemic vascular resistance and stimulates nitric oxide release thus exerting positive effects on vascular function. However, comparative studies on the vascular effects of third generation beta-blockers and AT1 receptor blockers are lacking. Aim of this randomized, double-blind study was to test the hypothesis of non-inferiority of nebivolol to irbesartan, both in association with hydrochlorothiazide, on endothelial function, arterial stiffness and central hemodynamic parameters in patients with arterial hypertension naïve on therapy. MethodsSixty-five patients were randomized to receive irbesartan/hydrochlorothiazide (150mg/12.5mgday) or nebivolol/hydrochlorothiazide (5mg/12.5mgday) for 8-weeks. Endothelial function, pulse wave velocity, augmentation index, central and brachial blood pressures were measured at baseline and at the end of the study. ResultsSystolic and diastolic central blood pressure, as well as brachial arterial pressure, decreased to a similar extent after both treatments. Similar changes in endothelial function between groups were detected at the end of the study. A significant reduction in pulse wave velocity, central blood pressure, and augmentation index adjusted for heart rate, was found in both the treatment groups at the end of the study, without significant differences between groups. ConclusionsThe results of this study confirm the hypothesis of non-inferiority of short-term treatment with nebivolol compared to irbesartan, both in association with hydrochlorothiazide, on endothelial function, arterial stiffness and central hemodynamic parameters in hypertensive patients naïve on therapy.

Direct renin inhibitor aliskiren in women with menopausal metabolic syndrome and arterial hypertension

Aim. To study the effectiveness of a direct renin inhibitor, aliskiren, in patients with menopausal metabolic syndrome (MMS), and to assess aliskiren effects on blood pressure (BP), carbohydrate and lipid metabolism parameters, microalbuminuria, and arterial stiffness. Material and methods. The study included 23 women with MMS, to whom aliskiren monotherapy (150-300 mg/d) was administered. At baseline and in the end of the study, anthropometry, carbohydrate and lipid metabolism parameters assessment, 24-hour BP monitoring, and arterial stiffness assessment by volume sphygmography were performed. Results. By the end of the study, most parameters of circadian BP profile significantly decreased. Target levels of systolic and diastolic BP were achieved in 80 % of the patients. There was a significant reduction in postprandial glucose levels. According to the volume sphygmography results, a decrease in arterial stiffness was accompanied by a significant reduction in pulse wave velocity and augmentation index, with normalization of the former parameter. Conclusion. Aliskiren therapy demonstrated not only high antihypertensive effectiveness in MMS patients, but also a reduction in postprandial glucose levels and arterial stiffness.

Effect of passive heat stress on arterial stiffness

Arterial compliance, the inverse of arterial stiffness, is a prognostic indicator of arterial health. Central and peripheral arterial compliance decrease with acute cold stress and may increase postexercise when exercise-induced elevations in core temperature are likely still to be present. Increased blood flow through the conduit arteries associated with elevated core temperature increases shear stress, which in turn releases nitric oxide and other endothelium-derived factors. These changes, in conjunction with supportive in vitro data, suggest that elevated core temperature may indirectly increase central and peripheral arterial compliance (i.e. decrease arterial stiffness). The purpose of this study was to test the hypothesis that increased core temperature decreases central and peripheral arterial stiffness, as measured with pulse wave velocity (PWV). Using Doppler ultrasound, carotid-femoral (central) and carotid-radial (peripheral) arterial PWVs were measured from eight subjects (age 37 ± 11 years; mass 68.8 ± 11.1 kg; height 171 ± 3 cm) before and during passive heat-stress-induced increases in core temperature of 0.47 ± 0.05, 1.03 ± 0.12 and 1.52 ± 0.07°C (i.e. baseline, 0.5, 1.0 and 1.5°C, respectively). Changes in PWV were evaluated with one-way repeated-measures ANOVA. When analysed as group means, neither central (677 ± 161, 617 ± 72, 659 ± 74 and 766 ± 207 cm s(-1); P = 0.12) nor peripheral PWV (855 ± 192, 772 ± 95, 759 ± 49 and 858 ± 247 cm s(-1); P = 0.56) changed as core temperature increased from baseline to 0.5, 1.0 and 1.5°C, respectively. However, individual changes in central (average r = -0.89, P < 0.05) and peripheral PWV (average r = -0.93, P < 0.05) with heat stress were significantly correlated with normothermic baseline PWV. In conclusion, these data suggest that the magnitude by which heat stress reduced PWV was predicated upon normothermic PWV, with the individuals having the highest normothermic PWV being most responsive to the heat-stress-induced reductions in PWV.

Mineralocorticoid Receptor Blockade does not Reduce Pulse Wave Velocity in Older Adults with Metabolic Syndrome

Arterial stiffness, an independent predictor of cardiovascular disease, is elevated in aging and metabolic syndrome (MS). We hypothesized that chronically elevated MR activation is partly responsible for increased arterial stiffness in aging/MS and that MR blockade would lead to greater decreases in arterial stiffness in middle-aged (MA) and older (O) adults with vs. without MS. PURPOSE: To examine the effect of 4-week MR blockade vs. placebo on arterial stiffness in MA/O adults with vs. without MS. METHODS: Using a randomized, double blind, crossover design, 100mg per day of Eplerenone (MR blocker) or placebo was administered orally for 4 weeks, with a 4-week washout, in 8 MA/O adults with (4 men & 4 women) vs. 15 (6 men & 9 women) without MS. Pulse wave velocity (PWV), a measure of arterial stiffness, was determined by positioning 2 Doppler flow meters at the suprasternal notch and femoral artery (aortic; AoPWV), femoral and posterior tibial artery (leg; LPWV), and brachial and radial artery (arm; ArPWV). RESULTS: MS risk factors expressed as an overall Z score were elevated in the MA/O adults with MS vs. without MS (0.7±0.2 vs. -0.4±0.1, P<0.0001) but age was similar between the 2 groups (63±3 vs. 64±1 years, P=0.7). Contrary to our hypothesis, PWV measures did not change in response to the MR blockade compared with placebo (AoPWV, 885±140 vs. 864±140 cm/sec, P=0.6; LPWV, 1364±48 vs. 1310±49 cm/sec, P=0.4; ArPWV, 1152±70 vs. 1153±±77 cm/sec, P=0.9) and the change in PWV was not different in the MA/O adults with vs. without MS (AoPWV, 816±241 vs. 934±139 cm/sec, P=0.8; LPWV, 1404±58 vs. 1270±39 cm/sec, P=0.7; ArPWV, 1140±102 vs. 1165±65 cm/sec, P=0.4). CONCLUSION: These results indicate that arterial stiffness in MA/O adults, independent of MS, is not modulated by MR blockade. Alternatively, the duration of the MR blockade may not be long enough to elicit changes in arterial stiffness as measured by PWV. Supported by AHA Grant 0865117F and NIH Grant AG032067.

Selective Endothelin-A Receptor Antagonism Reduces Proteinuria, Blood Pressure, and Arterial Stiffness in Chronic Proteinuric Kidney Disease

Proteinuria is associated with adverse cardiovascular and renal outcomes that are not prevented by current treatments. Endothelin 1 promotes the development and progression of chronic kidney disease and associated cardiovascular disease. We, therefore, studied the effects of selective endothelin-A receptor antagonism in proteinuric chronic kidney disease patients, assessing proteinuria, blood pressure (BP), and arterial stiffness, key independent, surrogate markers of chronic kidney disease progression and cardiovascular disease risk. In a randomized, double-blind, 3-way crossover study, 27 subjects on recommended renoprotective treatment received 6 weeks of placebo, 100 mg once daily of sitaxsentan, and 30 mg once daily of nifedipine long acting. Twenty-four-hour proteinuria, protein:creatinine ratio, 24-hour ambulatory BP, and pulse wave velocity (as a measure of arterial stiffness) were measured at baseline and week 6 of each treatment. In 13 subjects, renal blood flow and glomerular filtration rate were assessed at baseline and week 6 of each period. Compared with placebo, sitaxsentan reduced 24-hour proteinuria (-0.56±0.20 g/d; P=0.0069), protein:creatinine ratio (-38±15 mg/mmol; P=0.0102), BP (-3.4±1.2 mm Hg; P=0.0069), and pulse wave velocity (-0.64±0.24 m/s; P=0.0052). Nifedipine matched the BP and pulse wave velocity reductions seen with sitaxsentan but did not reduce proteinuria. Sitaxsentan alone reduced both glomerular filtration rate and filtration fraction. It caused no clinically significant adverse effects. Endothelin-A receptor antagonism may provide additional cardiovascular and renal protection by reducing proteinuria, BP, and arterial stiffness in optimally treated chronic kidney disease subjects. The antiproteinuric effects of sitaxsentan likely relate to changes in BP and renal hemodynamics.

Assessment of endothelial function by means of flow-mediated changes using pulse wave velocity.

Endothelial dysfunction is a leading cause of early development of cardiovascular diseases. Endothelial function can be assessed using ultrasound methods to watch the arterial flow-mediated dilation. It is also possible to find changes in pulse wave velocity (PWV) after induced ischemia related to the vessel diameter changes. Pre- and post-induced ischemia carotid-radial PWV was recorded in 226 hypertensive patients (150 women [63.5+/-12.4 years old] and 76 men [63.2+/-11.8 years old] and 55 healthy patients (38 women [63.1+/-12.6 years old] and 17 men [54.8+/-12.8 years old]). The authors considered normal endothelial function a PWV reduction of 5% from baseline. To assess nondependent endothelial dilation the authors performed carotid-radial PWV after sublingual administration of 5 mg of isosorbide dinitrate in a group of patients with abnormal flow-mediated dilation. A significant PWV reduction of 9.8% in normal patients and only 1.2% among hypertensive patients (P<.0005) was found. After sublingual isosorbide dinitrate intake the authors observed a greater fall in PWV (14%) than that observed in healthy people after induced ischemia. Carotid-radial PWV after induced ischemia decreased significantly in normal participants. No significant changes were observed in hypertensive patients. These results may offer a reliable tool to assess endothelial function in medium-size arteries.

Arterial Stiffness, Fatness, and Physical Fitness

Arterial distensibility and its converse stiffness have come of age as physiological concepts1 and now as a target for intervention. The central hypothesis sustained so far is that an individual’s “arterial stiffness” measured as aortic pulse wave velocity (PWV) is a convenient, integrated index of vascular pathology over a person’s life course, more precise and reliable than other risk factors individually. For example, blood pressure (BP), whether casual or 24 hour, is more sensitive to stimuli and, therefore, more variable. Arterial distensibility is in part dependent on BP, yet its prognostic power is because of its “independence” from BP, including pulse pressure.2 It appears to indicate the general burden of atherosclerotic disease and subclinical damage from multiple risk factors over time: the “wear and tear” of constant distension and recoil (part of “aging”), effects of smoking, lipid metabolism, (hyper)glycemia, ethnicity, how family history expresses itself, etc.3 European hypertension guidelines now include PWV as a recommended but optional measure. The relationship of arterial distensibility with cardiac function and structure, known as aorto-ventricular coupling, is tantalizing because, as a bioengineering feedback loop, cause and effect are still unclear. Many other key questions remain, most critically related to the natural history of arterial stiffness but also fundamental ones of basic structural biology in the vessel wall. A clue to the natural history of arterial stiffness is published in this issue of Hypertension , an Australian study of 9- to 10-year-old, generally prepubescent schoolchildren.4 The study shows a clear relationship among degree of body fat, physical fitness, and arterial stiffness, measured by carotid-femoral PWV. The link of PWV with fitness was not independent of body fat. Why should this article be of interest, being only cross-sectional, whereby association may well …

A comparison of atenolol and nebivolol in isolated systolic hypertension

Some beta-blockers are less effective in reducing central blood pressure than other antihypertensive drugs, which may explain the higher rate of events in subjects randomized to atenolol in recent trials. We hypothesized that nebivolol, a mixed beta-blocker/nitro-vasodilator, would be more effective than atenolol in reducing central blood pressure and augmentation index (AIx). The aim of the present study was to test this in a double-blind, randomized, cross-over study, in a cohort of subjects with isolated systolic hypertension. Following a 2-week placebo run-in, 16 never-treated hypertensive subjects received atenolol (50 mg), nebivolol (5 mg) and placebo, each for 5 weeks, in a random order. Seated brachial blood pressure and heart rate were measured. Aortic blood pressure, AIx and pulse wave velocity (PWV) were assessed non-invasively. The placebo-corrected fall in brachial pressure was similar between nebivolol and atenolol, as was the reduction in PWV (mean change +/- SEM: -1.0 +/- 0.3 and -1.2 +/- 0.2 m/s; P = 0.2). However, there was less reduction in heart rate (-19 +/- 2 versus -23 +/- 2 beats/min; P < 0.01) and increase in AIx (+6 +/- 1 versus +10 +/- 1%; P = 0.04), following nebivolol. Aortic pulse pressure was significantly lower (50 +/- 2 versus 54 +/- 2 mmHg; P = 0.02) after nebivolol. N-terminal pro-B-type natriuretic peptide (proBNP) rose on both drugs (100 +/- 33 versus 75 +/- 80 pg/ml; P < 0.01 for both, NS for comparison). Nebivolol and atenolol have similar effects on brachial blood pressure and aortic stiffness. However, nebivolol reduces aortic pulse pressure more than atenolol, which may be related to a less pronounced rise in AIx and bradycardia. Whether this will translate into differences in clinical outcome requires further investigation.

VASCULAR REMODELING AND HEART RATE VARIABILITY IN DIFFERENT ANTIHYPERTENSIVE THERAPIES

Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d), metoprolol tartrate (Egilok Retard, 50 mg/d) and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg) on pulse wave velocity (PWV), cardio-ankle vascular index (CAVI) and the sympathetic system activity. Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades) were examined. Biological age (BA) was determined by the linear regression and the vascular wall age (VWA) was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan). 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV) were determined before and at the end of the therapies. Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive. Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT). In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period. Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period. Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.

Mechanism(s) of Systolic Blood Pressure Reduction and Drug Therapy in Hypertension

Antihypertensive drug therapy is a major modality of cardiovascular (CV) disease prevention, especially for stroke, congestive heart failure, and renal insufficiency. Coronary risk is also consistently prevented by antihypertensive treatment, but to a lesser extent.1–4 The Prime Study2 has shown that drug-induced blood pressure (BP) reduction in hypertensive subjects is associated with a significant decrease of coronary risk. However, when treated and untreated subjects are compared, at any given value of systolic BP (SBP), this risk remains higher in treated than in untreated subjects, suggesting the persistence of residual coronary complications. Results of therapeutic trials also indicate that coronary risk is associated with a particular hemodynamic pattern in treated hypertensive subjects.3 Although diastolic BP (DBP) is significantly lowered by drug treatment to <90 mm Hg (80% of the patients), SBP remains above 140 mm Hg in 60%, indicating an increase of pulse pressure (PP), which is the difference between SBP and DBP.4 It is widely accepted that SBP and PP rise sharply with age and that this increase is a major manifestation of vascular aging and stiffening, which are now considered major predictors of CV risk, independent of the mean BP (MBP) level.4 The purpose of this review is to analyze the mechanism(s) of SBP in untreated and chronically treated hypertensive subjects and to determine which pathophysiological factors are susceptible to attenuating consistently coronary and CV complications in hypertensive populations. Ventricular ejection in humans is associated with 2 principal events. First, the coronary circulation is transiently interrupted, as the principal consequence of cardiac contraction, and, second, an acute shock of stroke volume against the aortic wall is observed (Figure 1). Then, the BP curve may be considered as a wave, which travels along the arterial tree at a given speed, the pulse wave velocity (PWV). …

Reduction in Arterial Stiffness With Angiotensin II Antagonism and Converting Enzyme Inhibition: A Comparative Study Among Malay Hypertensive Subjects With a Known Genetic Profile

Data comparing the effect of losartan and perindopril on aortic stiffness among hypertensive subjects without A(1166)C polymorphism was not available. The short-term and long-term effects of losartan (50 mg) and perindopril (4 mg) on aortic stiffness measured as carotid femoral pulse wave velocity (PWV) were compared in 39 middle-aged Malay subjects with mild-to-moderate hypertension in a 4-month, double-blind, randomized, controlled, parallel-design study. Four-month treatment with both drugs showed a significant reduction in blood pressure (BP) (P < .005) and PWV (P < .05) as compared to the baseline. On the other hand 1-month treatment showed a significant reduction in BP only in perindopril group (P < .05) but not in the losartan group. There was no significant reduction in pulse pressure and PWV after 1 month treatment by both drugs. No significant difference was seen in reduction in BP after 1 month and 4 months treatment between the two drugs. Similarly no significant difference was seen in reduction in PWV between the two drugs after 1 month (P = .613) and 4 months (P = .521) of treatment. Reduction in PWV by losartan (r = 0.470) and perindopril (r = 0.457) correlated significantly only with reduction in DBP (P < .05) and remained significant even after controlling for reduction in DBP (P < .05). Reduction in PWV by both losartan and perindopril was independent of reduction in BP by these drugs. These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.

Surrogate Measures of Arterial Stiffness

Recent epidemiological studies have shown that arterial stiffness, measured through carotid-femoral pulse wave velocity (PWV), has an independent predictive value for cardiovascular (CV) events in several populations, including patients with uncomplicated essential hypertension1,2 and type 2 diabetes.3 Arterial stiffness is thus an intermediate end point for CV events, predicting CV events independently of and beyond peripheral pulse pressure (PP). Peripheral PP, central PP, and augmentation index, which provide additional information on wave reflection, are considered “surrogates” of arterial stiffness, because their pathophysiological meaning is clearly different.4–6 Central PP and augmentation index are dependent on the speed of wave travel, the amplitude of reflected wave, the reflectance point, and the duration and pattern of ventricular ejection, especially with respect to change in heart rate and ventricular contractility. Aortic PWV, which is the speed of wave travel, represents intrinsically arterial stiffness, according to the Bramwell-Hill formula.4–6 Two articles7,8 in the present issue of Hypertension raise the issue of the predictive value of “surrogates of arterial stiffness” for CV events. Li et al7 studied the dynamic relationship between diastolic blood pressure (DBP0 and systolic blood pressure (SBP) in ambulatory blood pressure monitoring (ABPM) data throughout the day and calculated a novel index as 1− the regression slope of DBP on SBP. This index was named ambulatory arterial stiffness index (AASI) on the basis that “average distending BP …

Flow-mediated changes in pulse wave velocity: a new clinical measure of endothelial function

To test whether measuring hyperaemic changes in pulse wave velocity (PWV) could be used as a new method of assessing endothelial function for use in clinical practice. Flow-mediated changes in vascular tone may be used to assess endothelial function and may be induced by distal hyperaemia, while endothelium-mediated changes in vascular tone can influence PWV. These three known principles were combined to provide and test a novel method of measuring endothelial function by the acute effects of distal hyperaemia on upper and lower limb PWV (measured by a recently developed method). Flow-mediated changes in upper and lower limb PWV were compared in 17 healthy subjects and seven patients with stable chronic heart failure (CHF), as a condition where endothelial function is impaired but endothelium-independent dilator responses are retained. Corroborative measurements of PWV and brachial artery diameter responses to endothelium-dependent and -independent pharmacological stimuli were performed in a further eight healthy subjects. Flow-mediated reduction of PWV (by 14% with no change in blood pressure) was found in normal subjects but was almost abolished in patients with CHF. PWV responses appear to be inversely related to and relatively greater than brachial artery diameter responses. The method may offer potential advantages of practical use and sensitivity over conduit artery diameter responses to measure endothelial dysfunction.

Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture

Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid-femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10+/-0.02 mL/mm Hg, (P<0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7+/-0.2 m/s (P<0.001), augmentation index by 4.1+/-0.3% (P<0.001), and systolic blood pressure by 5+/-1 mm Hg (P<0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (P=0.59). In cell culture, ramiprilat decreased collagen deposition by >50% and increased elastin and fibrillin-1 deposition by >3- and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.

Nondipping Status Does Not Attenuate the Conjugated Estrogen-Induced Improvement in Aortic Stiffness in Postmenopausal Women with Untreated Hypertension

Whether the blunted nocturnal blood pressure (BP) fall alters the potential beneficial effects of estrogen replacement therapy (ERT) on arterial elastic properties in hypertensive postmenopausal women has not been clarified. The aim of this study was to determine the potential beneficial effects of ERT on arterial elastic properties and to investigate whether a blunted nocturnal BP fall could unfavorably modify the estrogen-induced alterations of large-artery stiffness in postmenopausal women with untreated essential hypertension. A total of 66 postmenopausal women with untreated essential hypertension underwent carotid-femoral pulse wave velocity (PWV) measurements at baseline and after 12 weeks of ERT with 0.625 mg conjugated estrogen. By 24-h ambulatory BP monitoring, women were classified according to dipping status (nondippers, n = 21; dippers, n = 45). The two groups were similar regarding age, body mass index, time since menopause, and lipidemic profile. Initially, nondippers compared to dippers, although they had significantly greater office systolic BP (SBP), 24-h SBP, daytime SBP and night-time SBP (by 5, 2, 3, and 19 mm Hg, respectively, P < .05 for all cases), did not differ regarding left ventricular (LV) mass index and aortic PWV (116 v 114 g/m2 and 8.40 v 7.95 cm/sec, respectively, P = NS for both cases). Use of ERT, without affecting the office SBP and DBP, reduced significantly the aortic PWV in both nondippers and dippers (by 1.28 and 1.50 cm/sec, respectively, P < .05 for both cases). However, these PWV reductions were not different between the two groups (P = NS). A multivariate analysis identified patient age and 24-h SBP as significant determinants of estrogen-induced aortic PWV reduction (P < .05). A blunted nocturnal BP fall does not attenuate the estrogen-induced favorable modifications of large artery elastic properties in hypertensive postmenopausal women. Whether these findings suggest that hypertensive women with ERT-induced attenuation of PWV represent a specific clinical subgroup of patients with possible ERT-associated cardiovascular benefit remains to be determined by properly randomized trials.

Effects of valsartan and nifedipine coat-core on systemic arterial stiffness in hypertensive patients

The aim of this study was to compare the effects of long-term antihypertensive treatment on brachial-ankle pulse wave velocity (PWV), a marker of systemic arterial stiffness, between angiotensin II receptor blocker valsartan and long-acting calcium channel blocker nifedipine coat-core. Forty-one patients (54 +/- 3 years of age, 20 men and 21 women) with essential hypertension (155 +/- 3/95 +/- 3 mm Hg) were randomly allocated to the treatment with valsartan (80 mg once daily) or nifedipine coat-core (20 mg once daily). Brachial-ankle PWV and 24-h ambulatory blood pressures (BP) were measured before and 3 months after treatment. Baseline data did not differ between the valsartan and nifedipine groups. The PWV also was similar between the groups (1669 +/- 65 v 1622 +/- 64 cm/sec). Three months of treatment similarly reduced resting systolic and diastolic BP (nifedipine, -18.4 +/- 4.2/-11.9 +/- 2.7 mm Hg; valsartan, - 17.4 +/- 3.3/-9.8 +/- 2.1 mm Hg, all P < .001). The PWV was significantly reduced compared with baseline values in the valsartan group (-195 +/- 42 cm/sec, P < 0.001) but not in the nifedipine group (-69 +/- 40 cm/sec, NS). The 24-h mean heart rate increased in the nifedipine group but remained unchanged in the valsartan group, although BP were similarly lowered for 24 h. A tachycardic response was associated with an increase or lesser reduction in PWV in a group treated with nifedipine (r = 0.584, P < .01). These data suggest that long-term treatment with valsartan could reduce arterial stiffness better than nifedipine-coat core. The favorable vascular effect of valsartan was due in part to its nonhypotensive effect. The expected decrease in arterial stiffness may be offset by reflex sympathetic activation in some patients treated with nifedipine.

Role of natriuretic peptides in regulation of conduit artery distensibility.

Arterial distensibility, assessed by the pulse-wave velocity (PWV), is an independent predictor of cardiovascular risk. We investigated whether natriuretic peptides, acting locally, modify conduit artery distensibility in vivo. All studies were conducted in anesthetized sheep (n = 18) by using a validated ovine hindlimb model. In brief, the PWV was calculated, with the use of the foot-to-foot methodology, from two pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Drugs were infused either proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath to control for any reflex changes in flow or sympathetic activation. First, the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were studied. Second, the role of endogenous ANP was investigated by infusing the natriuretic peptide receptor type A (NPRA)-selective receptor antagonist A71915. Third, A71915 was coinfused with ANP. Fourth, the NPRC-selective agonist cANF was infused. Infusion of CNP or des-[Gln18Ser19Gly20Leu21Gly22]-ANF-(4-23)-NH2 (cANF) had no effect on iliac PWV. However, infusion of ANP, and to a lesser degree BNP, resulted in a reduction in PWV (-9%; P < 0.01 and -6%; P < 0.05, respectively). A71915 increased iliac PWV from 2.97 +/- 0.13 to 3.06 +/- 0.13 m/s; P < 0.01. Coinfusion of A71915 with ANP completely abolished the effects of ANP (P < 0.01). Importantly, ANP-BNP infusion via the sheath did not alter PWV. In conclusion, ANP, and to a lesser extent BNP, modify large artery distensibility via the NPRA receptor. Neither CNP nor cANF altered PWV, suggesting that the NPRB and NPRC receptors do not acutely influence distensibility in vivo.

Total homocysteine is not a determinant of arterial pulse wave velocity in young healthy adults

Aims: Hyperhomocysteinaemia has been associated with reduced pulse wave velocity (PWV) in patients with end-stage renal disease and in those with hypertension. The aim of this study was to examine the association between total homocysteine (tHcy) concentrations, the biochemical and genetic determinants of tHcy and PWV in healthy young adults. Methods and results: A total of 489 subjects aged 20–25 years participated. A fasting blood sample was taken and PWV measured using a non-invasive optical method. tHcy did not correlate with PWV, whether assessed at the aorto-iliac segment ( P = 0.18), the aorto-radial segment ( P = 0.39) or the aorto-dorsalis-pedis segment ( P = 0.22). When tHcy was classified into normal (<15) and high (≥15 μmol/l), PWV did not differ between the two groups at any segment. PWV did not differ by MTHFR C677T or NOS3 G894T genotype, even when smoking and folate sub-groups were considered. Considering aortic PWV as a dependent variable, stepwise regression analysis showed that the only parameter entering the model for all segments was systolic blood pressure (aorto-iliac, P < 0.001; aorto-radial, P = 0.01; aorto-dorsalis-pedis, P = 0.001). Age, sex, COL1A1 genotype and triglycerides entered the model significantly for two of three segments. Conclusion: This study shows that arterial PWV is not associated with tHcy in a healthy young population.