Ageing, hypertension and aortic valve stenosis - Understanding the series circuit using cardiac magnetic resonance and applanation tonometry.

BACKGROUND: Aortic stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload, but rather, functions as a series circuit, with important contributions from both the valve and vasculature. Patients with AS are typically elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizeable, and yet, quantifying this to-date has been difficult to determine. We compared measurement of aortic pressure, flow and global LV load using a cardiac magnetic resonance (CMR)/applanation tonometry (AT) technique to uncouple ventriculo-arterial (VA) interactions. METHODS: 20 healthy elderly patients and 20 with AS underwent a CMR/AT protocol. CMR provided LV volume and aortic flow simultaneously with AT pressure acquisition. Aortic pressure was derived by transformation of the AT waveform. Systemic vascular resistance (SVR) and global LV load were determined as the relationship of pressure to flow in the frequency domain. Values from both cohorts were compared. RESULTS: AS patients were older (p â€‹< â€‹0.01) albeit with no significant difference in brachial or central aortic pressure. SVR (14228 vs 19906 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) and load (740 vs 946 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) were higher in patients with AS, whilst aortic peak flow velocity was lower (38 vs 58 â€‹cm/s; p â€‹< â€‹0.01). CONCLUSIONS: Quantification of aortic pressure, flow velocity and global LV load using a simultaneous CMR/AT technique is able to demonstrate the progressive effects of hypertension and aortic stiffening with advanced age and valvular stenosis. This technique may help to better identify future patients at risk of VA coupling mismatch after correction of AS.

The menopausal transition does not appear to accelerate age-related increases in arterial stiffness.

OBJECTIVE: Arterial stiffness is an independent marker of cardiovascular risk that increases with age, hypertension, diabetes and hyperlipidemia, both for men and women (although more pronounced in women). This study was designed to establish whether menopause augments the age-dependent change. METHODS: The study evaluated pulse wave analysis and pulse wave velocity using applanation tonometry in 468 women (aged 40-80 years) sampled from the general population. In multiple linear regression models, age was the predominant correlate of increasing aortic augmentation pressure (p < 0.0001), augmentation index (p < 0.0001), augmentation index adjusted to a heart rate of 75 beats/min (p < 0.0001) and carotid-femoral pulse wave velocity (p < 0.0001). RESULTS: Analysis of covariance showed no significant difference in adjusted mean of augmentation pressure, augmentation index or pulse wave velocity between menopause groups (pre-, peri-, postmenopause). Adjusted means of augmentation pressure and pulse wave velocity were comparable between women on hormone therapy (n = 130) and non-users (n = 338). CONCLUSIONS: The results of the present study challenge the assertion by some researchers that menopause accelerates age-dependent changes in arterial stiffness.

Arterial stiffness as a cause of cognitive decline and dementia: a systematic review and meta-analysis.

BACKGROUND: Although arterial stiffness has recently been confirmed as a predictor of cardiovascular disease, the association between arterial stiffness and cognitive decline is less clear. AIM: We performed a systematic review and meta-analysis to examine the evidence for large artery stiffness as a cause of cognitive decline and dementia. METHOD: Electronic databases were systematically searched until September 2011 for studies reporting on the longitudinal relationship between any validated measure of large artery stiffness and cognitive decline or dementia. Meta-analysis was performed on four studies investigating the association between aortic pulse wave velocity and a decline in Mini-Mental State Examination scores. RESULTS: Six relevant longitudinal studies were located, conducted over an average of 5 years follow up. Arterial stiffness was predictive of cognitive decline in five/six studies. In meta-analysis, higher aortic stiffness predicted lower Mini-Mental State Examination scores within the sample (ß=-0.03, 95% confidence interval (CI): -0.06 to 0.01, n= 3947), although studies were not all homogeneous, and statistical heterogeneity was present (I(2) = 71.9%, P= 0.01). Removal of one study with a relatively younger cohort and lower median aortic stiffness found higher aortic stiffness to significantly predict cognitive decline (ß=-0.04, 95% CI: -0.07 to -0.01, n= 3687) without evidence of heterogeneity (I(2) = 9.5%, P= 0.33). There was little research investigating the effects of aortic stiffness on the development of dementia. CONCLUSION: Aortic stiffness was found to predict cognitive decline in both qualitative review and quantitative analysis.

Treatment of hypertension in patients 80 years of age or older.

Isolated systolic hypertension (ISH) is present in the majority of persons who reach the age of 80 years, and is caused directly or indirectly by stiffening of the aorta and large central elastic arteries. Until recently, there was no consensus on whether or not persons over 80 should be treated, according to principles established for the younger group examined in the Systolic Hypertension in the Elderly Project (SHEP). The recent Hypertension in the Very Elderly Trial (HYVET) study endorses application of SHEP to most such subjects. This review describes the background to SHEP and HYVET, including concepts of hypertension and interpretation of blood pressure values. It describes the effects of age on arterial stiffness, and effects of stiffness on the heart, large arteries and microvessels in brain and kidneys as the basis of symptomatic disease. It describes logic of therapy with newer antihypertensives which indirectly affect arterial stiffness and form the basis of therapy in older persons. It proposes how, with what and in whom antihypertensive therapy could be offered in persons over age 80.

Prolonged mechanical systole and increased arterial wave reflections in diastolic dysfunction.

OBJECTIVE: To evaluate whether left ventricular ejection time indexed for heart rate (left ventricular ejection time index (LVETI)) and arterial wave reflections (augmented pressure (AP)) are increased in patients with diastolic dysfunction (DD). DESIGN: Prospective observational study. SETTING: University teaching hospital providing primary and tertiary care. SUBJECTS: 235 consecutive patients undergoing left heart catheterisation were categorised as having definite DD, possible DD or no DD (controls) on the basis of their left ventricular end diastolic pressures and N-terminal brain natriuretic peptide concentrations. MAIN OUTCOME MEASURES: LVETI and AP were prospectively assessed non-invasively by radial applanation tonometry. In addition, all patients underwent comprehensive echocardiography, including tissue Doppler imaging of mitral annulus velocity in early diastole (E'). RESULTS: LVETI was longer in patients with definite DD than in patients with possible DD and in controls (433.6 (SD 17.2), 425.9 (17.9) and 414.3 (13.6) ms, respectively, p < 0.000001). Arterial wave reflections were higher in definite DD than in possible DD and control groups (AP was 19.4 (SD 8.9), 15.2 (8.0) and 10.7 (6.8) mm Hg, respectively, p < 0.000001). In receiver operating characteristic curve analysis, LVETI detected DD as well as echocardiography (E:E'). Area under the curve for LVETI to differentiate patients with definite DD from normal controls was 0.81 (95% CI 0.72 to 0.89, p < 0.0001). In multivariable logistic regression analysis, LVETI added significant independent power to clinical and echocardiographic variables for prediction of DD. CONCLUSIONS: Mechanical systole is prolonged and arterial wave reflections are increased in most patients with DD. Rapid non-invasive assessment of these parameters may aid in confirming or excluding DD.

Reality of out of hospital cardiac arrest.

The high mortality rates associated with out of hospital cardiac arrest, particularly those occurring in the home, stress the need for early treatment in the form of publicly accessible external defibrillators.

Benefit of glyceryl trinitrate on arterial stiffness is directly due to effects on peripheral arteries.

OBJECTIVE: To determine how the vasodilator glyceryl trinitrate (GTN) alters arterial stiffness and improves left ventricular afterload. METHODS: Ascending aortic pressure waves were measured with fluid filled catheters of high fidelity in 50 patients undergoing cardiac surgery, before cardiopulmonary bypass, both before and after intravenous infusion of GTN. In all 50 patients, wave reflection was identifiable as a secondary boost to late systolic pressure, permitting the pressure wave to be separated into a primary component, attributable to left ventricular ejection and properties of the proximal aorta, and a secondary component, attributable to reflection of the primary wave from the peripheral vasculature. RESULTS: GTN infusion caused no change in amplitude of the primary wave (mean (SD) 0.0 (1.4) mm Hg, not significant) but substantial reduction (14.6 (9.6) mm Hg, p < 0.0001) in amplitude of the secondary reflected wave. Fall in mean pressure was attributable to a mix of arteriolar and venous dilatation, with relative contributions unable to be separated. CONCLUSION: Favourable effects of GTN on arterial stiffness can be attributed to effects on peripheral muscular arteries, causing reduction in wave reflection. Results conform with previous invasive studies on vasodilator agents and their known effects on calibre and compliance of muscular arteries.

The second peak of the radial artery pressure wave represents aortic systolic pressure in hypertensive and elderly patients.

BACKGROUND: Simultaneous measurement of ascending aorta and radial artery pressure shows that mean and diastolic pressures (DP) are in close agreement in normotensive adults, while systolic pressures (SP) are not. However, in the aortic pressure wave, a second systolic peak appears with increasing age and increases to represent the SP by age 32 yr, while in the radial artery, a second systolic deflection appears by age 40 yr. We suggest that the second radial systolic wave, sometimes seen during radial arterial pressure monitoring in older hypertensives, represents the aortic SP. We set out to evaluate whether the aortic and radial second systolic peaks agree, and since doubts exist about the agreement between aortic and radial DP in elderly hypertensive patients, we also assessed that relationship. METHODS: We compared simultaneously recorded radial and aortic pressures from 21 anaesthetized adult patients using identical fluid-filled pressure measuring systems. CONCLUSIONS: The second radial pressure peak agreed with that in the aorta within a mean of 0.6 (SD 1.5) mm Hg. The difference between DP in the aorta and radial artery was -1.4 (2) mm Hg. The radial-aortic SP and pulse pressure differences were 5.9 (7.6) and 7.3 (7.6) mm Hg, respectively. These results confirm that when the radial artery pressure wave shows a first and second, or only a second systolic shoulder/peak (on the right side of the pressure wave), the second represents the maximal ascending aortic SP, and that the radial and aortic DP are equivalent, even in older hypertensive patients.

Arterial pressure waveforms in hypertension.

Measurement of arterial pressure waveforms in hypertension enhances information on underlying disease and mechanisms, since it provides all information in the waveform, and not just the extreme limits of the waveform (systolic and diastolic pressure) which are obtained from the brachial artery with a cuff sphygmomanometer. Such studies of the waveform reawaken the clinical use of sphygmography which was used in clinical practice and for life insurance examinations before the cuff sphygmomanometer was introduced by Riva-Rocci in 1896. Modern advances include use of accurate electronic tonometers for pressure recording, application of knowledge on wave transmission in the upper limb, and use of computer techniques to manipulate, store and retrieve data. It is now possible to determine the aortic pressure waveform, and so, left ventricular pressure throughout systole, with an accuracy which is limited only by the inaccuracy of the sphygmomanometer cuff. Clinical application assists in recognition of spurious systolic hypertension as a condition which needs no treatment, and in grading the severity of hypertension for any given value of cuff systolic and diastolic pressure. Application also permits tailoring of drug therapy for the underlying abnormality of increased peripheral resistance or increased stiffness of the large elastic arteries. Information obtained also assists in prognosis.

Quantification of glyceryl trinitrate effect through analysis of the synthesised ascending aortic pressure waveform.

OBJECTIVE: To establish through analysis of the radial pressure pulse waveform the dose dependent effects of glyceryl trinitrate (GTN) on properties of different blood vessels. DESIGN: Radial pulse waveform was measured in randomised order before, during a five hour application of a GTN patch delivering 0.104-0.625 mg/h, and for two hours after patch removal. The radial pressure waveform (Millar applanation tonometer) was convolved into an ascending aortic wave using a generalised transfer function (SphygmoCor process) enabling measurement of aortic systolic, diastolic, pulse, mean, and augmented pressure and left ventricular ejection duration in addition to standard brachial cuff pressures. SETTING: Fu Wai and Ren Ming hospitals in Beijing, China. PATIENTS: 46 recumbent hospitalised patients aged 56 (9) years, awaiting electrophysiological or other diagnostic studies, fasting, and with other treatments suspended. MAJOR OUTCOME MEASURES: Conventional brachial pressure measures and data from the synthesised aortic pulse. RESULTS: There was no consistent change in heart rate or brachial pressures except for a decrease in systolic and pulse pressures (p < 0.01) at dose > 0.416 mg/h. In contrast, there were substantial and significant (p < 0.0001) decreases in aortic systolic, pulse, and augmented pressures at all doses, mean pressure (p < 0.001) at doses > 0.416 mg/h, and ejection duration (p < 0.001) at doses > 0.208 mg/h. CONCLUSIONS: Pulse waveform analysis exposes dose dependent effects of GTN on the aortic waveform, suggesting muscular conduit arterial dilatation with reduced wave reflection at the lowest dose, arteriolar dilatation and decreased peripheral resistance at the highest dose, and venous dilatation at the intermediate dose.

Can a clinically useful aortic pressure wave be derived from a radial pressure wave?

BACKGROUND: The information contained in arterial pressure waveforms is probably underused by most clinicians who manage critically ill patients. It is not generally known that an aortic pressure wave can be synthesized by applying a generalized transfer function to the radial arterial pressure wave. We validated a commercially available system, SphygmoCo (PWV Medical, Sydney). METHODS: Ascending aortic pressure waves were synthesized and comparisons were made between the synthesized aortic waveforms, the measured aortic and radial arterial waveforms. Ascending aortic pressure waves (catheter-tip manometer) and radial artery pressure waves (short fluid-filled catheter) were recorded simultaneously in 12 patients with angina pectoris (age 62-76 years) undergoing cardiac catheterization. Patients were studied at rest, following midazolam, sublingual nitroglycerin and during Valsalva manoeuvres. RESULTS: Both midazolam and nitroglycerin lowered mean arterial pressure but nitroglycerin caused a more selective decrease in the measured and synthesized aortic systolic pressures than in the radial artery pressure. The synthesized aortic systolic pressure was less, by 6-8 mm Hg (SD 2-3) and the synthesized aortic diastolic pressure greater, by 4 mm Hg (SD 2). Despite these differences in pulse pressure, the synthesized waveform tracked the measured waveform before and during interventions. CONCLUSIONS: By deriving an aortic waveform from the radial pulse, monitoring of left ventricular afterload can improve without more invasive means.

Pressure-altering agents affect central aortic pressures more than is apparent from upper limb measurements in hypertensive patients: the role of arterial wave reflections.

The pressure pulse does not have the same amplitude in central and peripheral arteries, but it is amplified toward the periphery; the degree of this amplification depends principally on wave reflection. Despite the conventional clinical and epidemiological focus on peripheral pressures, the most physiologically relevant pressures for both cardiac and vascular effects are central pressures. The reflected wave contributes differently in the configuration of the peripheral and central pressure waveform. Therefore, we hypothesized that agents that alter wave reflections could have an unequal effect on central and peripheral pressures in hypertensive patients. Thus, the effect of caffeine was investigated in 10 hypertensive subjects according to a randomized, placebo-controlled, double-blind, crossover design. Central aortic pressures and wave reflection were assessed with applanation tonometry and pulse wave analysis. After caffeine, augmentation index and augmented pressure increased by 4.6%, (P<0.005) and 5.7 mm Hg (P<0.001), respectively, indicating increased effect of wave reflection from the periphery. The increase in aortic systolic pressure was greater compared with that in radial artery pressure at 30 minutes (25%) and marginally greater at 60 minutes (21%). Furthermore, the increase in aortic pulse pressure was greater at 30 and 60 minutes (34% and 40%, respectively). The intensified reflected wave after caffeine was largely responsible for the disparate effect between central and peripheral pressures by boosting the peak of the central and not of the peripheral waveform. This study shows that pressure-altering agents might affect central pressures more than is apparent from the corresponding upper limb values because of the concomitant changes in wave reflection.

Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform.

Pressure wave reflection in the upper limb causes amplification of the arterial pulse so that radial systolic and pulse pressures are greater than in the ascending aorta. Wave transmission properties in the upper limbs (in contrast to the descending aorta and lower limbs) change little with age, disease, and drug therapy in adult humans. Such consistency has led to use of a generalized transfer function to synthesize the ascending aortic pressure pulse from the radial pulse. Validity of this approach was tested for estimation of aortic systolic, diastolic, pulse, and mean pressures from the radial pressure waveform. Ascending aortic and radial pressure waveforms were recorded simultaneously at cardiac surgery, before initiation of cardiopulmonary bypass, with matched, fluid-filled manometer systems in 62 patients under control conditions and during nitroglycerin infusion. Aortic pressure pulse waves, generated from the radial pulse, showed agreement with the measured aortic pulse waves with respect to systolic, diastolic, pulse, and mean pressures, with mean differences <1 mm Hg. Control differences in Bland-Altman plots for mean+/-SD in mm Hg were systolic, 0.0+/-4.4; diastolic, 0.6+/-1.7; pulse, -0.7+/-4.2; and mean pressure, -0.5+/-2.0. For nitroglycerin infusion, differences respectively were systolic, -0.2+/-4.3; diastolic, 0.6+/-1.7; pulse, -0.8+/-4.1; and mean pressure, -0.4+/-1.8. Differences were within specified limits of the Association for the Advancement of Medical Instrumentation SP10 criteria. In contrast, differences between recorded radial and aortic systolic and pulse pressures were well outside the criteria (respectively, 15.7+/-8.4 and 16.3+/-8.5 for control and 14.5+/-7.3 and 15.1+/-7.3 mm Hg for nitroglycerin). Use of a generalized transfer function to synthesize radial artery pressure waveforms can provide substantially equivalent values of aortic systolic, pulse, mean, and diastolic pressures.

Spurious systolic hypertension in youth.

Six young men diagnosed with systolic hypertension had normal carotid pressure wave contours, normal synthesized aortic pressure wave contours and normal diastolic and mean pressures in upper limb arteries. Elevated brachial systolic pressure was caused by a high narrow systolic peak of the pressure wave. This was attributed to amplification of the pressure wave between the ascending aorta and upper limb (radial and brachial) arteries that is associated with attainment of full body length and very distensible arteries. These young men were not truly hypertensive. Exaggeration of the upper limb systolic peak represented an extreme of the normal pressure wave pattern in youth, where amplification is greater than in childhood or in older subjects. This phenomenon accounts for the rapid increase in systolic pressure between the ages of 5 and 20 years, and the relative plateau in systolic pressure between the ages of 20 and 45 years that is seen in population studies.