Association of 24-h central hemodynamics and stiffness with cardiovascular events and all-cause mortality. The VASOTENS Registry.

OBJECTIVES: In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients. METHODS: In 591 hypertensive patients (mean age 58 ±â€Š14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years. RESULTS: One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P = 0.0001], female sex [1.57 (1.05, 2.33), P = 0.027], CV disease [2.22 (1.50, 3.29), P = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P = 0.027], PWV [1.59 (1.07, 2.36), P = 0.022], or AIx [1.59 (1.08, 2.36), P = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P = 0.924], AIx [1.06 (0.66, 1.69), P = 0.823], and central PP [1.18 (0.76, 1.82), P = 0.471], were not significant predictors in multivariate analyses. CONCLUSIONS: In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics.

Relationship between heart rate and central aortic blood pressure: implications for assessment and treatment of isolated systolic hypertension in the young.

Isolated systolic hypertension in the young (ISHY) remains a challenging problem, partly due to the differences in central aortic pressure observed in studies investigating ISHY. The fundamental relationship between heart rate and central aortic pressure, and more precisely, the relationship between heart rate and amplification of central aortic pressure in the periphery, underpins the assessment and, as a consequence, the treatment of ISHY. Physiology warrants that an increase in heart rate would lead to increased amplification of the pressure pulse between the aorta and the brachial artery. Heart rate generally decreases with age, in particular over the first two decades of life. Thus, a higher heart rate in the young would result in higher pulse pressure amplification, and therefore an elevated brachial systolic pressure would not necessarily translate to elevated aortic systolic pressure. However, elevated heart rate is not a consistent feature in ISHY, and studies have shown that ISHY can present with either high or low central aortic systolic pressure. In this brief review, we summarize the physiological aspects underlying the relationship between heart rate and central aortic blood pressure and its amplification in the brachial artery, how this relationship changes with age, and examine the implications of these effects on the assessment and treatment of ISHY.

Potential of coconut oil and medium chain triglycerides in the prevention and treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-ß pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.

Age-related changes of shape and flow dynamics in healthy adult aortas: A 4D flow MRI study.

BACKGROUND: Abnormal flow dynamics play an early and causative role in pathologic changes of the ascending aorta. PURPOSE: To identify: 1) the changes in flow, shape, and size that occur in the ascending aorta with normal human ageing and 2) the influence of these factors on aortic flow dynamics. STUDY TYPE: Retrospective. SUBJECTS: In all, 247 subjects (age range 19-86 years, mean 49 ± 17.7, 169 males) free of aortic or aortic valve pathology were included in this study. Subjects were stratified by youngest (18-33 years; n = 64), highest (>60 years, n = 67), and the middle two quartiles (34-60 years, n = 116). FIELD STRENGTH/SEQUENCE: Subjects underwent a cardiac MRI (3T) exam including 4D-flow MRI of the aorta. ASSESSMENT: Aortic curvature, arch shape, ascending aortic angle, ascending aortic diameter, and the stroke volume normalized by the aortic volume (nSV) were measured. Velocity, vorticity, and helicity were quantified across the thoracic aorta. STATISTICAL TESTS: Univariate and multivariate regressions were used to quantify continuous relationships between variables. RESULTS: Aortic diameter, ascending aortic angle, shape, and curvature all increased across age while nSV decreased (all P < 0.0001). Systolic vorticity in the mid arch decreased by 50% across the age range (P < 0.0001), while peak helicity decreased by 80% (P < 0.0001). Curvature tightly governs optimal flow in the youngest quartile, with an effect size 1.5 to 4 times larger than other parameters in the descending aorta, but had a minimal influence with advancing age. In the upper quartile of age, flow dynamics were almost completely determined by nSV, exerting an effect size on velocity and vorticity >10 times that of diameter and other shape factors. DATA CONCLUSION: Aortic shape influences flow dynamics in younger subjects. Flow conditions become increasingly disturbed with advancing age, and in these conditions nSV has a more dominant effect on flow patterns than shape factors. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:90-100.

Effect of increasing heart rate on finger photoplethysmography fitness index (PPGF) in subjects with implanted cardiac pacemakers.

Finger photoplethysmography (PPG) is a noninvasive method that measures blood volume changes in the finger. The PPG fitness index (PPGF) has been proposed as an index of vascular risk and vascular aging. The objectives of the study were to determine the effects of heart rate (HR) on the PPGF and to determine whether PPGF is influenced by blood pressure (BP) changes. Twenty subjects (78±8 years, 3 female) with permanent cardiac pacemakers or cardioverter defibrillators were prospectively recruited. HR was changed by pacing, in a random order from 60 to 100 bpm and in 10 bpm increments. At each paced HR, the PPGF was derived from a finger photoplethysmogram. Cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) were derived from the finger arterial pressure waveform. Brachial blood pressure (BP) was measured by the oscillometric method. This study found that as HR was increased from 60 to 100 bpm, brachial diastolic BP, brachial mean BP and CO were significantly increased (p<0.01), whilst the PPGF and SV were significantly decreased (p<0.001). The effects of HR on the PPGF were influenced by BP, with a decreasing HR effect on the PPGF that resulted from a higher BP. In conclusion, HR was a significant confounder for PPGF and it must be taken into account in analyses of PPGF, when there are large changes or differences in the HR. The magnitude of this effect was BP dependent.

Effects of instructed meditation augmented by computer-rendered artificial virtual environment on heart rate variability.

Previous research has supported the use of virtual reality (VR) to decrease stress, anxiety, perceptions of pain, and increase positive affect. However, the effect of VR on blood pressure (BP) and autonomic function in healthy populations have not been explored. This study quantifies the effect of instructed meditation augmented by a virtual environment (VE) on BP and heart rate variability (HRV) during rest and following physical (isometric handgrip) or mental (serial sevens subtraction) stress. Sixteen healthy participants underwent all conditions, and those that responded to the stress tests were included in the analysis of stress recovery. Results showed that under resting conditions, VE had no significant effect on BP or HRV when compared to seated rest and the VE video on a 2D screen. Following serial sevens, VE maintained the increased low frequency (LF) power of HRV $( 66 \pm 4$ normalized units (n.u.)) compared to seated rest $( 55 \pm 5\mathrm {n}$.u., $\mathrm {p}=0.0060)$; VE maintained the decreased high frequency (HF) power of HRV $( 34 \pm 4\mathrm {n}$.u.) compared to seated rest $( 44 \pm 5\mathrm {n}$.u., $\mathrm {p}=0.014)$; and VE maintained the increased LF/HF ratio $( 2.4 \pm 0.5)$ compared to seated rest $( 1.6 \pm 0.3$, $\mathrm {p}=0.012)$. Hence, after mental stress, VE sustains the increased sympathetic drive and reduced parasympathetic drive. VE may act as a stimulatory driver for autonomic activity and BP. Further studies are required to investigate the effect of different types of VE on BP and autonomic function.

Systolic time intervals assessed from analysis of the carotid pressure waveform.

OBJECTIVE: The timing of mechanical cardiac events is usually evaluated by conventional echocardiography as an index of cardiac systolic function and predictor of cardiovascular outcomes. We aimed to measure the systolic time intervals, namely the isovolumetric contraction time (ICT) and pre-ejection period (PEP), by arterial tonometry. APPROACH: Sixty-two healthy volunteers (age 47 ± 17 years) and 42 patients with heart failure and reduced ejection fraction were enrolled (age 66 ± 14 years). Pulse waves were recorded at the carotid artery by arterial tonometry together with simultaneous aortic transvalvular flow by Doppler-echocardiography, synchronized by electrocardiographic gating. The ICT was determined from the time delay between the electrical R wave and the carotid pressure waveform, after adjustment for the pulse transit time from the aortic valve to the carotid artery site, estimated by an algorithm based on the carotid-femoral pulse wave velocity. The PEP was evaluated by adding the electrical QR duration to the ICT. MAIN RESULTS: The ICT derived from carotid pulse wave analysis was closely related to that measured by echocardiography (r = 0.90, p < 0.0001), with homogeneous distribution in Bland-Altman analysis (mean difference and 95% confidence interval = 0.2 from -14.2 to 14.5 ms). ICT and PEP were higher in cardiac patients than in healthy volunteers (p < 0.0001). The ratio between PEP and left ventricular ejection time was related to the ejection fraction measured with echocardiography (r = 0.555, p < 0.0001). SIGNIFICANCE: The timing of electro-mechanical cardiac events can be reliably obtained from the carotid pulse waveform and carotid-femoral PWV, evaluated using arterial tonometry. Systolic time intervals assessed with this approach showed good agreement with measurements performed with conventional echocardiography and may represent a promising additional application of arterial tonometry.

Quantum theory of mass potentials.

Probabilistic formalism of quantum mechanics is used to quantitatively link the global scale mass potential with the underlying electrical activity of excitable cells. Previous approaches implemented methods of classical physics to reconstruct the mass potential in terms of explicit physical models of participating cells and the volume conductor. However, the multiplicity of cellular processes with extremely intricate mixtures of deterministic and random factors prevents the creation of consistent biophysical parameter sets. To avoid the uncertainty inherent in physical attributes of cell ensembles, we undertake here a radical departure from deterministic equations of classical physics, instead applying the probabilistic reasoning of quantum mechanics. Crucial steps include: (1) the relocation of the elementary bioelectric sources from a cellular to a molecular level; (2) the creation of microscale particle models in terms of a non-homogenous birth-and-death process. To link the microscale processes with macroscale potentials, time-frequency analysis was applied for estimation of the empirical characteristic functions for component waveforms of electroencephalogram (EEG), eye-blink electromyogram (EMG), and electrocardiogram (ECG). We describe universal models for the amplitude spectra and phase functions of functional components of mass potentials. The corresponding time domain relationships disclose the dynamics of mass potential components as limit distribution functions produced by specific microscale transients. The probabilistic laws governing the microscale machinery, founded on an empirical basis, are presented. Computer simulations of particle populations with time dependent transition probabilities reveal that hidden deterministic chaos underlies development of the components of mass potentials. We label this kind of behaviour "transient deterministic chaos".

Cuffless Estimation of Blood Pressure: Importance of Variability in Blood Pressure Dependence of Arterial Stiffness Across Individuals and Measurement Sites.

OBJECTIVE: Measuring arterial pulse transit time (PTT) to estimate blood pressure (BP) without conventional brachial cuff-based measurement is not new, but is a focus of current wearable technologies research. Much research pertains to efficient, accurate sensing of artery-related waveforms, yet the relationship between PTT and BP receives less attention despite being key for accurate BP estimation. This study investigated BP/PTT calibration by quantifying anatomical site variability (n = 10, 3 female, age 30 9 years) and individual variability ( n = 103, 50 female, age 53 22 years). METHODS: BP and pulse wave velocity (PWV) were measured in both seated and supine. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and carotid-finger-volume PWV (cvPWV) were measured with the wrist and hand positioned at the level of the upper thigh to achieve the same hydrostatic pressure effect across all measurements. RESULTS: The postural change invoked a small (4 7 mmHg) change in brachial diastolic BP with an additional 27 2 mmHg change in hydrostatic pressure. cfPWV decreased in the supine position (1.75 0.17 m s-1, p < 0.001), but crPWV and cvPWV were more variable. The calibration term (BP/PWV) across the sample population varied from 6.6 to 98.3 mmHg sm-1 (mean 22 14 mmHg sm-1) and was correlated with age, heart rate, diastolic and pulse pressure, and weight. These variables did not explain the majority of the variability (R2 = 0.248). CONCLUSION: There is anatomical site and between-individual variability in the calibration term for BP estimation from PTT. SIGNIFICANCE: Using and accurately calculating hydrostatic changes in BP within the individual may be one method to increase the accuracy of this calibration term.

Characterisation of cardiac autonomic function in multiple sclerosis based on spontaneous changes of heart rate and blood pressure.

BACKGROUND: Prevalence of cardiovascular autonomic dysfunction (CAD) in multiple sclerosis (MS) varies between studies. Cardiac autonomic function is usually assessed by cardiovascular reflex tests. We hypothesized that MS is associated with CAD, quantifiable by non-invasive means including quantification of baroreceptor sensitivity (BRS) and heart rate variability. METHODS: In this study a comprehensive suite of cardiovascular autonomic tests based only on the spontaneous changes of heart rate and blood pressure was applied to 23 MS patients and age and gender-matched controls. From 5-min continuous non-invasive recording of the electrocardiogram and blood pressure, heart-rate, blood pressure, and autonomic function variables were calculated. Analysis included heart rate variability in the time domain, heart rate and blood pressure variability in the frequency domain, and baroreceptor sensitivity in both the time and frequency domain. RESULTS: BRS measured by the frequency technique in high frequency band was found to be significantly lower in MS (16 ±â€¯9 ms/mmHg) compared to controls (29 ±â€¯17 ms/mmHg) (p < 0.05). Also mean of BRS modulus in MS averaged 15 ±â€¯8 ms/mmHg which is significantly lower compared to controls (25 ±â€¯15 ms/mmHg) (p < 0.05). Systolic blood pressure variability in the high frequency band (0.15-0.5 Hz) was found to be significantly higher in the MS compared to controls (5.8 ±â€¯16.7 mmHg2 vs. 1.3 ±â€¯0.8 mmHg2) (p < 0.05). CONCLUSIONS: The results, using techniques novel to MS investigation, showed diminished baroreceptor reflex and impaired sympathetic function using frequency domain systolic blood pressure variability analysis.

Characteristics and outcome for heart failure patients with mid-range ejection fraction.

AIMS: The aim of this study was to compare precipitants, presenting symptoms and outcomes of patients with heart failure and mid-range ejection fraction (HFmrEF), heart failure and preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) in an Australian cohort. METHODS: We divided 5236 patients in the Management of Cardiac Failure program in Northern Sydney Australia, into HFmrEF (n = 780, 14.9%), HFpEF (n = 1956, 37.4%) and HFrEF (n = 2500, 47.8%), using a cutoff left ventricular ejection fraction of 40-49, at least 50 and less than 40%, respectively. RESULTS: For most characteristics, the HFmrEF patients were intermediate. Hypertension among the HFrEF, HFmrEF and HFpEF groups was present in 50.6, 61.7 and 68.9%, respectively; age more than 85 years was present in 35.1, 37.6 and 42.2%; atrial fibrillation in 35.3, 44.2 and 49.9%; and elevated serum creatinine (>100 µmol/l) in 59.2, 55.6 and 51.0%. For ischemic heart disease and ischemia as a precipitant of admission, HFmrEF patients were similar to the HFrEF group, and more common than in HFpEF. Mortality rates were not significantly different between the three groups. Readmission rates were highest for HFpEF (40.2%), followed by HFmrEF (42.4%) and HFrEF (45.4%), largely due to differences in nonheart failure readmission. CONCLUSION: Clinically, HFmrEF represents an intermediate phenotype, with the exception of resembling HFrEF with a higher incidence of ischemic heart disease.

Effects of pacing modality on noninvasive assessment of heart rate dependency of indices of large artery function.

Studies investigating the relationship between heart rate (HR) and arterial stiffness or wave reflections have commonly induced HR changes through in situ cardiac pacing. Although pacing produces consistent HR changes, hemodynamics can be different with different pacing modalities. Whether the differences affect the HR relationship with arterial stiffness or wave reflections is unknown. In the present study, 48 subjects [mean age, 78 ± 10 (SD), 9 women] with in situ cardiac pacemakers were paced at 60, 70, 80, 90, and 100 beats per min under atrial, atrioventricular, or ventricular pacing. At each paced HR, brachial cuff-based pulse wave analysis was used to determine central hemodynamic parameters, including ejection duration (ED) and augmentation index (AIx). Wave separation analysis was used to determine wave reflection magnitude (RM) and reflection index (RI). Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Pacing modality was found to have significant effects on the HR relationship with ED (P = 0.01), central aortic pulse pressure (P = 0.01), augmentation pressure (P < 0.0001), and magnitudes of both forward and reflected waves (P = 0.05 and P = 0.003, respectively), but not cfPWV (P = 0.57) or AIx (P = 0.38). However, at a fixed HR, significant differences in pulse pressure amplification (P < 0.001), AIx (P < 0.0001), RM (P = 0.03), and RI (P = 0.03) were observed with different pacing modalities. These results demonstrate that although the HR relationships with arterial stiffness and systolic loading as measured by cfPWV and AIx were unaffected by pacing modality, it should still be taken into account for studies in which mixed pacing modalities are present, in particular, for wave reflection studies.

Heart Rate Dependency of Large Artery Stiffness.

Carotid-femoral pulse wave velocity (cfPWV) quantifies large artery stiffness, it is used in hemodynamic research and is considered a useful cardiovascular clinical marker. cfPWV is blood pressure (BP) dependent. Intrinsic heart rate (HR) dependency of cfPWV is unknown because increasing HR is commonly accompanied by increasing BP. This study aims to quantify cfPWV dependency on acute, sympathovagal-independent changes in HR, independent of BP. Individuals (n=52, age 40-93 years, 11 female) with in situ cardiac pacemakers or cardioverter defibrillators were paced at 60, 70, 80, 90, and 100 bpm. BP and cfPWV were measured at each HR. Both cfPWV (mean [95% CI], 0.31 [0.26-0.37] m/s per 10 bpm; P<0.001) and central aortic diastolic pressure (3.78 [3.40-4.17] mm Hg/10 bpm; P<0.001) increased with HR. The HR effect on cfPWV was isolated by correcting the BP effects by 3 different methods: (1) statistically, by a linear mixed model; (2) mathematically, using an exponential relationship between BP and cross-sectional lumen area; and (3) using measured BP dependency of cfPWV derived from changes in BP induced by orthostatic changes (seated and supine) in a subset of subjects (n=17). The BP-independent effects of HR on cfPWV were quantified as 0.20 [0.11-0.28] m/s per 10 bpm (P<0.001, method 1), 0.16 [0.11-0.22] m/s per 10 bpm (P<0.001, method 2), and 0.16 [0.11-0.21] m/s per 10 bpm (P<0.001, method 3). With a mean HR dependency in the range of 0.16 to 0.20 m/s per 10 bpm, cfPWV may be considered to have minimal physiologically relevant changes for small changes in HR, but larger differences in HR must be considered as contributing to significant differences in cfPWV.

ACEIs for cardiovascular risk reduction--have we taken our eye off the ball?

BACKGROUND: Hypertensive patients have an increased risk of cardiovascular (CV) events. There is debate whether angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) offer similar reductions in CV risk. OBJECTIVE: This article discusses some of the recent evidence for the prevention of CV events and mortality with ACEIs and ARBs, and the rationale for using an ACEI as the preferred agent for comprehensive CV risk reduction in specific patient populations. DISCUSSION: ACEIs and ARBs are structurally and functionally very different agents; they are not interchangeable. Prescriptions for ARBs are increasing in Australia. However, clinical trial evidence suggests possible advantages of ACEIs over ARBs, particularly in terms of survival benefit. Many patients with hypertension have other CV risk factors that may affect medication choice. The aim of treatment should not be just to lower blood pressure, but to reduce absolute CV risk.

Long-term effectiveness of extended-release nitrate for the treatment of systolic hypertension.

Isosorbide mononitrate (ISMN) is effective in the short-term for decreasing systolic blood pressure, pulse pressure, and pulse wave reflection in patients with systolic hypertension. To determine whether tolerance negates the efficacy of this nitrate in the long-term, a placebo-controlled study was performed in which ISMN was withdrawn briefly in a group of patients (n=16) who had received extended-release ISMN 60 to 120 mg once daily for 16 to 109 months. Blood pressure and wave reflection were determined by 24-hour ambulatory recorder and tonometer, respectively. During a 4-hour delay of the regular morning dose of ISMN, mean systolic blood pressure was higher than with the regular ISMN dosing schedule (P<0.0001). The maximum placebo-active difference was 16+/-4 mm Hg. The corresponding difference in augmentation index (a measure of pulse wave reflection) corrected for heart rate was 25+/-4% (P<0.001). The difference in pulse pressure was 13+/-3 mm Hg (P<0.001). There was no significant difference in diastolic blood pressure. For a subgroup (n=12) in which the effects of a single ISMN dose had been determined at the initiation of regular ISMN therapy, the mean change in augmentation index was of similar magnitude to that observed in their initial study. Thus, tolerance does not seriously diminish the antihypertensive efficacy of ISMN used as adjunct therapy in the chronic treatment of systolic hypertension. This agent lowers systolic blood pressure sufficiently to achieve therapeutic goal in some patients refractory to conventional treatment regimens.

Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave.

BACKGROUND: Deficiency of nitric oxide (NO) production has been implicated in the pathogenesis of increased pulse wave reflection associated with systolic hypertension. We investigated the effects on systolic blood pressure (BP) and pulse wave contour of two nitrate donors, isosorbide mononitrate (ISMN) and L-arginine. METHODS: The subjects were 14 elderly patients chronically treated with antihypertensive agents. In seven of the subjects, agents causing angiotensin II (AII) inhibition (angiotensin-converting enzyme [ACE] inhibitor or AT(1) receptor antagonist, or both) were used. Study entry required systolic BP of 150 to 200 mm Hg, and aortic pulse wave augmentation more than 15 mm Hg. Pharmacodynamic responses to ISMN, L-arginine, and ISMN plus L-arginine, were assessed in double-blind crossover studies by standard sphygmomanometry and applanation tonometry. RESULTS: Peripheral systolic BP, aortic systolic BP, and the aortic augmentation index were decreased (P <.001) by ISMN, irrespective of AII inhibition. L-arginine enhanced these effects (P <.001) in the subjects without AII inhibition, but not in those receiving AII inhibitors. Given without ISMN or AII inhibitors, L-arginine decreased peripheral systolic BP, but to a lesser extent than ISMN. CONCLUSIONS: L-arginine has potential value as an adjunct to ISMN in combination with antihypertensive therapy in elderly patients with systolic hypertension. However, when given with single-dose ISMN, its vasodilator activity may overlap with that of AII inhibitors. Future studies of L-arginine in conjunction with chronic continuous ISMN dosing are warranted.

Effects of isosorbide mononitrate and AII inhibition on pulse wave reflection in hypertension.

The aortic pulse wave contour in isolated systolic hypertension often shows a prominent reflection peak, which combines with the incident wave arising from cardiac ejection so as to widen pulse pressure. We investigated the effects of an extended-release nitrate preparation and of 2 angiotensin II (AII) inhibitors (an AII receptor antagonist and an ACE inhibitor) on the aortic pulse wave contour and systemic blood pressure in hypertensive subjects with high augmentation index caused by exaggerated pulse wave reflection. Two double-blind, randomized, placebo-controlled crossover studies were carried out in a total of 16 elderly patients with systolic hypertension resistant to conventional antihypertensive therapy. In 1 study, pharmacodynamic responses to single doses of placebo, isosorbide mononitrate, eprosartan, and captopril were determined; in the other, single-dose isosorbide mononitrate and placebo were compared in subjects treated with AII inhibitors at baseline. Blood pressure was measured by sphygmomanometry and pulse wave components by applanation tonometry at the radial artery. All 3 agents were shown to decrease brachial systolic blood pressure, aortic systolic blood pressure, and aortic pulse pressure. Qualitative effects on the aortic pulse wave contour differed: augmentation index was not significantly altered by either captopril or eprosartan but was decreased (P<0.0001) by approximately 50% of the placebo value with isosorbide mononitrate in both study groups. We propose that isosorbide mononitrate corrected the magnified wave reflection in systolic hypertension of these elderly patients by an effect that was distinct from that exercised by either acute or chronic AII inhibition.