In patients with uncomplicated essential hypertension, cardiac output remains within normal ranges and intravascular volume is normal or low, assuming the presence of a sufficient Windkessel effect ...and usual resistance and compliance calculations. However, mean circulatory pressure is elevated in these patients. In addition, vascular resistance is augmented, and most importantly, the viscoelasticity of the cardiovascular system is substantially impaired. Such considerations are essential to understanding the mechanisms behind carotid-femoral arterial stiffness, a major risk factor in individuals with hypertension. Arterial stiffness, measured from pulse wave velocity, is substantially increased in hypertension even independently of blood pressure levels. Structural vascular changes and endothelial dysfunction are consistently associated with vessel impairments in animal models of hypertension. Increased arterial stiffness has a major effect on pulse pressure (the difference between systolic and diastolic blood pressure), wave reflections, kidney function, and above all, cardiovascular risk. This increased cardiovascular risk is particularly deleterious in patients with hypertension and/or type 2 diabetes mellitus, who are at risk of both renal and cardiovascular events. In this Review, we discuss the importance of arterial stiffness in the diagnosis and management of hypertension and the need for new approaches for the treatment of hypertension in patients with or without diabetes and/or renal impairment.
Abstract
BACKGROUND
Arterial stiffness—typically assessed from non-invasive measurement of pulse wave velocity along a straight portion of the vascular tree between the right common carotid and ...femoral arteries—is a reliable predictor of cardiovascular risk in patients with essential hypertension.
METHODS
We reviewed how carotid-femoral pulse wave velocity increases with age and is significantly higher in hypertension (than in age- and gender-matched individuals without hypertension), particularly when hypertension is associated with diabetes mellitus.
RESULTS
From the elastic aorta to the muscular peripheral arteries of young healthy individuals, there is a gradual but significant increase in stiffness, with a specific gradient. This moderates the transmission of pulsatile pressure towards the periphery, thus protecting the microcirculatory network. The heterogeneity of stiffness between the elastic and muscular arteries causes the gradient to disappear or be inversed with aging, particularly in long-standing hypertension.
CONCLUSIONS
In hypertension therefore, pulsatile pressure transmission to the microcirculation is augmented, increasing the potential risk of damage to the brain, the heart, and the kidney. Furthermore, elevated pulse pressure exacerbates end-stage renal disease, particularly in older hypertensive individuals. With increasing age, the elastin content of vessel walls declines throughout the arterial network, and arterial stiffening increases further due to the presence of rigid wall material such as collagen, but also fibronectin, proteoglycans, and vascular calcification. Certain genes, mainly related to angiotensin and/or aldosterone, affect this aging process and contribute to the extent of arterial stiffness, which can independently affect both forward and reflected pressure waves.
In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as ...age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions.
Aims To calculate robust quantitative estimates on the predictive value of central pressures and derived central haemodynamic indices for cardiovascular (CV) outcomes and all-cause mortality by ...meta-analysis of longitudinal studies. Methods and results We meta-analysed 11 longitudinal studies that had employed measures of central haemodynamics and had followed 5648 subjects for a mean follow-up of 45 months. The age- and risk-factor-adjusted pooled relative risk (RR) of total CV events was 1.088 (95% CI 1.040–1.139) for a 10 mmHg increase of central systolic pressure, 1.137 (95% CI 1.063–1.215) for a 10 mmHg increase of central pulse pressure (PP), and 1.318 (95% CI 1.093–1.588) for a 10% absolute increase of central augmentation index (AIx). Furthermore, we found that a 10% increase of central AIx was associated with a RR of 1.384 (95% CI 1.192–1.606) for all-cause mortality. When compared with brachial PP, central PP was associated with marginally but not significantly higher RR of clinical events (P = 0.057). Conclusion Central haemodynamic indexes are independent predictors of future CV events and all-cause mortality. Augmentation index predicts clinical events independently of peripheral pressures, while central PP has a marginally but not significantly (P = 0.057) better predictive ability when compared with peripheral PP.
Aging incurs aortic stiffening and dilation, but these changes are less pronounced in peripheral arteries, resulting in stiffness and geometry gradients influencing progression of the forward and ...reflected pressure waves. Because premature arterial aging is observed in ESRD, we determined the respective roles of stiffness and aortic geometry gradients in 73 controls and 156 patients on hemodialysis. We measured aortic pulse wave velocity (PWV) and brachial PWV to evaluate the stiffness gradient (brachial PWV/aortic PWV)(0.5) and ascending aortic and aortic bifurcation diameters to assess aortic taper (ascending aortic diameter/aortic bifurcation diameter). The global reflection coefficient was estimated from characteristic impedance and vascular resistance. Cox proportional hazard models were used to determine mortality risk. The age-associated increase in aortic PWV was higher in patients (P<0.001). In controls, aortic ascending and bifurcation diameters increased with age, with an unchanged aortic taper. In patients on hemodialysis, age did not associate with increased ascending aortic diameter but did associate with increased aortic bifurcation diameter and decreased aortic taper, both of which also associated with abdominal aortic calcifications and smaller global reflection coefficient (P<0.001). In patients, multivariate models revealed all-cause and cardiovascular mortality associated with age, aortic PWV, and aortic bifurcation diameter with high specificity and sensitivity. Using stiffness gradient, aortic taper, or global reflection coefficient in the model produced similar results. Thus, whereas aortic stiffness is a known independent predictor of mortality, these results indicate the importance of also evaluating the aortic geometry in patients on hemodialysis.
Arterial stiffness and impedance gradients are known to influence pressure wave propagation and macrovascular-microvascular interactions. We studied the association between the carotid-femoral ...arterial stiffness gradient and the systemic reflection coefficient (N=393); of this population, 246 also underwent assessment of forward/backward pressure wave propagation and microvascular pulsatile pressure transmission (MPPT). Hemodynamic parameters were measured noninvasively. From peripheral vascular resistance and characteristic impedance, we estimated the systemic reflection coefficient and MPPT on peripheral and cardiac microcirculation in age-matched, sex-matched and body mass index-matched individuals with (n=147) or without (n=98) hypertension. The arterial stiffness gradient, systemic reflection coefficient, and correlations between the arterial stiffness gradient and age or blood pressure were similar in both populations. MPPT was higher in hypertension (
<0.0001), and the subendocardial viability (Buckberg) index lower (
<0.0001). In both populations, the systemic reflection coefficient and arterial stiffness gradient were significantly associated with changes in MPPT and the subendocardial viability index. Despite similar systemic reflection coefficients, the carotid reflected pressure and MPPT were higher in hypertension. Maintaining the systemic reflection coefficient within normal ranges was, therefore, insufficient to compensate for higher carotid forward pressure waves which, in hypertension, were associated with increased aortic stiffness (
<0.0001) and higher stroke volume (
=0.0365). Independently of cardiovascular risk, hypertension-induced changes have a weighted effect on MPPT, although insufficient to compensate for increased forward pressure waves. In hypertension, elevated aortic stiffness negatively affects the arterial stiffness gradient and systemic reflection coefficient but positively affects forward pressure.
Arterial aging can be attributed to two different pathophysiological changes--increase in arterial stiffness and disturbed wave reflections. The capacity of the aorta to absorb the force exerted by ...the left ventricular ejection and dampen pulsatile flow becomes diminished with advancing age, owing to the progressive hardening of the arterial wall. These changes contribute to increase blood pressure, mainly systolic blood pressure and pulse pressure, which can trigger cardiovascular events. Understanding the pulsatile arterial hemodynamics that elevate cardiovascular risk has led to the use of pharmacological therapies, which prevent arterial stiffness and reduce wave reflections, and improve cardiovascular morbidity and mortality. Antifibrotic agents, such as those that block the renin-angiotensin-aldosterone pathway, are often given in association with diuretics, calcium-channel blockers, or both, but not with standard beta-blockers. Consistent reductions in cardiovascular outcomes obtained using these agents can be predicted through noninvasive measurements of central systolic blood pressure and pulse pressure.
Abstract Hypertension is strongly associated with cardio/cerebrovascular diseases, e.g. myocardial infarction, stroke, and heart failure, which are main causes of cardiovascular morbidity and ...mortality. In hypertensive subjects, cardiovascular risk reduction is mainly associated with reduction in brachial systolic blood pressure (SBP). As it was shown in controlled and long-term therapeutic trials, it is possible to produce a selective SBP reduction through a specific “de-stiffening” strategy. This means that SBP reduction is obtained independently of mean arterial pressure change, using a significant and selective reduction of wave reflections and/or aortic stiffness. The procedure is especially effective in decreasing central systolic and pulse pressures, which were shown to be major determinants of long-term outcome. As some concerns associated with decreasing in diastolic blood pressure to low values (so called “J-curve” phenomenon) have been raised recently the de-stiffening strategy appears to be especially attractive. Most of the protocols used to de-stiffen large arteries required the administration of a renin–angiotensin–aldosterone system inhibitor, which frequently was associated with a diuretic and/or a calcium antagonist, but not with a classic beta-blocker. These protocols were evaluated in randomized controlled trials and showed significant reduction in cardiovascular risk, particularly in comparison with beta-blockers.
Arterial stiffness is an independent predictor of cardiovascular events and mortality in hypertensive patients. The influence of different antihypertensive drug classes on improving arterial ...stiffness beyond blood pressure reduction is not widely available. We aimed to determine whether the artery stiffness can be improved because of antihypertensive treatments independently of blood pressure lowering.
We conducted a meta-analysis of individual data from 15 randomized, controlled, double-blind, parallel group trials performed in our laboratory between 1987 and 1994. The primary endpoint was the changes of carotid-femoral pulse wave velocity (PWV) after treatment in 294 patients with mild-to-moderate essential hypertension untreated. Treatments tested were placebo (n = 88), angiotensin-converting enzyme inhibitors (ACEIs) (n = 75), calcium antagonists (n = 75), beta-blocker (n = 30), and diuretic (n = 26).
In the short-term and long-term trials, PWV decreased significantly by -0.75 and -1.3 m/s in the active treatment group compared with by +0.17 and -0.44 m/s in the placebo group, respectively. Active treatment was independently related to the changes in PWV and explained 5 and 4% of the variance in the short-term and long-term trials, respectively. In the short-term trials, ACEIs were more effective than calcium antagonists and placebo on improving arterial stiffness. In the long-term trials, ACEI, calcium antagonists, beta-blocker, and diuretic reduced significantly PWV compared to placebo.
Our study shows that antihypertensive treatments improve the arterial stiffness beyond their effect on blood pressure.
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